BIOCHEMICAL SOCIETY

Managing Editor D. C. WATTS

London:The Biochemical Society © 1984

CONTENTS i i i

C o n t e n t s Volume 12, Part 1

D E V E L O P M E N T A L , G E N E T I C A N D E N V I R O N M E N ­T A L A S P E C T O F D R U G B I O T R A N S F O R M A T I O N A N D C O N J U G A T I O N Acknowledgements Introduction Backword and forward Intra- and extra-cellular formation of metabolites from

chemically reactive species Mechanism of metabolic activation of ronidazole, a 5-

nitroimidazloe Xenobiotic acyl-coenzymes A: critical intermediates in the

biochemical pharmacology and toxicology of carboxylic acids

Effects of binding of amphipathic compounds to carrier proteins on their enzymic biotransformation by mem­brane-bound enzymes

Glucuronidation and glucosidation reactions in aquatic species in boreal regions

Competition between sulphation and glucuronidation in the rat in vivo: enzyme kinetics and pharmacokinetics of conjugation

Peroxidase-catalysed metabolism of drugs and carcinogens Alterations in thiol and calcium-ion homoeostasis during

hydroperoxide and drug metabolism in hepatocytes Measurement of the oxidation rate of volatile alkanes: a

new and non-invasive procedure for testing the drug-metabolizing capacity of the liver

Interaction of aliphatic carbamates with hepatocytes (by title only)

Multiple forms of mouse glutathione 5-transferases Cysteine conjugate ß-lyase and the thiomethyl shunt Glucocorticoid sulphotransferases in rats and other animal

species Nitroreduction of clonazepam in human foetal liver

microsomes and hepatocyte cultures Enzymology and regulation of xenobiotic and steroid

metabolism in placenta Influence of glucocorticoids and polycyclic aromatic hydro­

carbons on hepatic drug-metabolizing enzyme develop­ment during the perinatal period

Regulation of microsomal testosterone 15a-hydroxylase activity in inbred mouse liver and kidney

Regulation of enzyme development: a commentary The biosynthesis and induction of microsomal UDP-

glucuronyltransferase in avian liver Differential induction and glycosylation of UDP-

glucuronosyltransferase Differential induction of UDP-glucuronosyltransferases

and their 'permanent induction' in pre-neoplastic rat liver Induction of xenobiotic-metabolizing enzymes by trans-

stilbene oxide and 2-acetylaminofluorene: observations on enzyme induction by drugs

Dynamics of the localization of drug metabolizing enzymes in tissues and cells

Apparent anomalies in the resolution of cytochrome P-450 isoenzymes by gel electrophoresis

1

B . B U R C H E L L & I . STEVENSON 1 G . J . DUTTON 2 J . R . G I L L E T T E , S. S. L A U & T . J . MONKS 4

A . Y . H . Lu, P. G . WISLOCKI, E . S. BAGAN, 7 R . W . WANG, J . S. WALSH & G . T . MIWA

J . C A L D W E L L 9

K . P. M . H E I R W E G H 11

O . HÄNNINEN, P. LINDSTRÖM-SEPPÄ, 13

U . KOIVUSAARI, M . VÄISÄNEN, A . JULKUNEN & R . JUVONEN G . J . M U L D E R , J . R . DAWSON & K . S. PANG 17

P. MOLDEUS, R . LARSSON, D . ROSS & B . ANDERSSON 20 S. ORRENIUS, H . THOR & G . BELLOMO 23

H . REMMER & A . E L . M . GHARAIBEH 28

J . W . BRIDGES 3 0

C . - Y . G . L E E 30 W . B . JAKOBY & J . STEVENS 3 3 S. S. SINGER 3 5

D . - R . PENG , I . PETTERS & A . R A N E 39

O. PELKONEN & M . PASANEN 42

J . E . A . L E A K E Y 44

A . H . NEIMS, R . L. H A W K E , L. RAYNOR & G . SINGH 45

A . M . NEMETH 48 B . B U R C H E L L , S. K E N N E D Y , M . JACKSON & 50 L. M C C A R T H Y I . S. OWENS & P. I . MACKENZIE 54

K . W . BOCK, W . LILIENBLUM, D . U L L R I C H & 5 5 G . FISCHER J . W . D E P I E R R E , J . SEIDEGÄRD, R . MORGENSTERN, 58 L. B A L K , J . MEIJER & A . ASTRÖM

C . R . W O L F , A . BUCHMANN, T . F R I E D B E R G , 60 E . M O L L , W . D . KUHLMANN, H . W . K U N Z & F . OESCH W . L E V I N , J . E . SHIVELY, P . - M . Y U A N & 62 D . E . R Y A N

Vol. 12

iv CONTENTS

Factors involved in the regulation of the levels and activities of rat liver cytochromes P-450

Cloning and characterization of NADPH-cytochrome P-450 oxidoreductase gene (by title only)

Regulation of glutathione S-transferase mRNAs by pheno-barbitol and 3-methylcholanthrene: analysis using cDNA probes

A new polymorphism of hepatic drug oxidation in man: family studies on rates of formation of antipyrine metabolites

Multiple forms of human cytochrome P-450 UDP-glucuronosyltransferase deficiency in man and

animals Biliary excretion of the dimethyl ester of bilirubin in

heterozygous (Jj) and normal ( J J ) Gunn rats Acetylation pharmacogenetics: profiles of arylamine phar­

macology and toxicology in a genetic mouse model Drug metabolism and tropical disease

Drug conjugation in clinical toxicology Cloning genes that encode inducible forms of P-450

Polymorphisms in drug metabolism: implications for drug utilization

Cloning of cDNA coding for a rat liver protein whose expression is subject to gender-specific regulation by xenobiotics

Kinetic properties of rat liver UDP-glucuronylsyltransfer-ase during ontogenesis

BOOK REVIEWS

F. P . G U E N G E R I C H 68

C . KASPER 71

C B . PICKETT, C . A . TELAKOWSKI-HOPKINS, 71 L . ARGENBRIGHT & A . Y . H . L U

E . S. VESSELL & M . B . PENNO 74

A . R . BOOBIS & D . S. DAVIES 78 J. R O Y CHOWDHURY, N . R O Y CHOWDHURY 81 & I . M . ARIAS

G . B . O D E L L , G . R . G O U R L E Y & W . MOGILEVSKY 83

W. W . W E B E R , T . A . H U L T I N & D . A . MORGOTT 87

A . BRECKENRIDGE, K . AWADZI, D . J. BACK, 90 G . EDWARDS, H . G I L L E S , M . ORME & S. WARD L . F. PRESCOTT 96 D . W . NEBERT, M . NEGISHI, Y . - T . C H E N & 99 R . H . T U K E Y

F. SJÖQVIST 101

I . R . PHILLIPS, E . A . SHEPHARD & A . ASHWORTH 103

L . K I F F E L , J. MAGDALOU & G . SIEST 105

107

C o n t e n t s Volume 12, Part 2

T H E NINTH K E I L I N MEMORIAL L E C T U R E The evolution and function of biological molecular assem­

blies: from catalase to viruses

T H E T W E N T I E T H COLWORTH MEDAL L E C T U R E D N A : sequence, structure and supercoiling

604th MEETING, CAMBRIDGE Colloquium: Carbohydrate Transport in Micro-organisms Binding-protein-mediated transport systems in Escherichia

coli Sugar-proton transport systems of Escherichia coli

Reconstitution of the lactose carrier from mutant and parent cells of Escherichia coli

Tightness of energy coupling during carbohydrate uptake in eukaryotic micro-organisms

Relation between the protonmotive force and solute transport in bacteria

Regulation of sugar transport by the bacterial phosphoenol-pyruvate: glucose phosphotransferase system

The role of the phosphoenolpyruvate-phosphotransferase system in inducer exclusion

M . G. ROSSMANN 115

D . M . J . L I L L E Y 127

W . Boos 141

P. J. F. HENDERSON, S. BRADLEY, 146 A . J . S. MACPHERSON, P. HORNE, E . O . DAVIS, K . R . DARUWALLA & M . C . JONES-MORTIMER T . H . WILSON, D . SETO-YOUNG & S. B E D U 148

A . A . E D D Y 150

W . N. KONINGS, R . OTTO , B. T E N BRINK, 152 G. T . ROBILLARD, M . G. L. E L F E R I N K & K . J . H E L L I N G WERF D . Fox, M . KUKURUZINSKA, K . D . -F . L iu , 155 N. D . MEADOW, D . SAFFEN & S. ROSEMAN H . L. KORNBERG, P . BRITTON, 157 M . . C JONES-MORTIMER & L. G. L E E

1984

CONTENTS

Colloquium: Growth Factors Studies on the structure and function of the epidermal-

growth-factor receptor Uptake and intracellular processing of epidermal-growth-

factor-receptor complexes Transforming growth factors: sources, properties and

possible roles in normal and malignant cell growth control

Nerve Growth Factor-an enigma still?

Symposium: Enterotoxins and Anti-toxins Enterotoxins and ion transport The mechanism of action of Escherichia coli heat-stable

toxin The ADP-ribosyltransferase activity of cholera toxin and

Escherichia coli heat-labile toxin Genetics of enterotoxin production in Escherichia coli Cellular location of enterotoxin in Escherichia coli Enteric diseases in animals caused by Escherichia coli: their

control and prevention Clostridium difficile enterotoxin (toxin A) : new results

Clostridium perfringens enterotoxin: a brief review Bacillus cereus enterotoxins: present status Present status of cholera vaccines

Antimotility drugs in the treatment of acute diarrhoea Opiate agonists and enterotoxins a2-Adrenergic agonists and enterotoxins

Inhibition of cholera toxin-induced secretion by neuroleptics

Colloquium: The Application of Recombinant DNA Tech­nology to Enzymology and Membrane Transport Processes

Cloning enzyme genes for overproduction

Use of recombinant D N A techniques to study D N A repair in Escherichia coli

Cloning and sequence analysis of the pyruvate and 2-oxoglutarate dehydrogenase complex genes of Escherichia coli

Cloning and sequencing of the gene encoding NADP-specific glutamate dehydrogenase in Neurospora crassa

Genetic dissection of tyrosyl-tRNA synthetase

Directed mutagenesis as a technique to study protein function: application to ^-lactamase

Probing the catalytic mechanism of yeast triose phosphate isomerase by site-specific mutagenesis

Molecular mechanisms of bacterial periplasmic transport systems

Genes for bacterial and mitochondrial ATP synthase

Potassium transport in Escherichia coli: genetic and bio­chemical characterization of the K +-transporting ATPase

Isolation and manipulation of genes coding for energy-transducing enzymes from Neurospora crassa and Escheri­chia coli

Molecular and genetic aspects of the fumarate reductase of Escherichia coli

M . GREGORIOU & A . R . R E E S 160

J . BEARDMORE & C . R . HOPKINS 165

K . D . BROWN & D . M . B L A K E L E Y 168

B . E . C . BANKS 173

M . C . RAO & M . F I E L D 177 H . R . DE JONGE 180

C . J . COULSON, P. M . NASSAU & R . M . T A I T 184

H . R . SMITH 187

T . R . HIRST, L . L . RANDALL & S. J . S. HARDY 189

C WRAY 191

J . STEPHEN, S. C . REDMOND, T . J . M I T C H E L L , 194 J . K E T L E Y , D . C . A . CANDY, D . W . BURDON & R . DANIEL B . A . BARTHOLOMEW & M . F . STRINGER 195

R . J . G I L B E R T & J . M . KRAMER 198

M . M . L E V I N E , R . E . B L A C K , M . L . CLEMENTS & 200 J . B . K A P E R S. HUGHES 202 B . K . SANDHU, A . D . PHILLIPS & P. J . M I L L A 205 P. M . NEWSOME, M . N . BURGESS, M . R . BURGESS, 208 G . D . HOLMAN & S. R . NAHORSKI J . - J . LARSEN, A . V . CHRISTENSEN & J . H Y T T E L 211

T . ATKINSON, D . A . BARSTOW, S. A . JONES, 215 N . P. MINTON & R . F . SHERWOOD

P. T . EMMERSON, I . D . HICKSON, H . M . ARTHUR, 218 K . E . ATKINSON, D . BRAMHILL, P. F I N C H & L . HUTTON J . R . GUEST, M . G . DARLISON, M . E . SPENCER & 220 P. E . STEPHENS

J . R . S. FINCHAM & J . A . KINNAIRD 223

G . WINTER, P. CARTER, M . M . Y . W A Y E , 224 D . M . BLOW, A . J . WILKINSON, J . - P . SHI & A . R . FERSHT G . DALBADIE-MCFARLAND, A . D . R I G G S & 226 J . H . RICHARDS G . A . PETSKO, R . C . DAVENPORT, J R . , D . F R A N K E L 229 & U. L . RAIBHANDARY

C F . HIGGINS 232

J . E . W A L K E R , G . F A L K , N . J . G A Y & 234 V . L . J . T Y B U L E W I C Z

W . EPSTEIN, L . WIECZOREK, A . SIEBERS & 235 K . ALTENDORF

W . SEBALD, H . ARENDS & J . E . G . M C C A R T H Y 236

S. T . C O L E 237

Vol. 12

vi CONTENTS

COMMUNICATIONS

605th M E E T I N G , S T R A T H C L Y D E COMMUNICATIONS

CHARING CROSS M E E T I N G Symposium: Use of Liposomes in Medicine Brenda E. Ryman Liposomes: bags of challenge Interaction of liposomes with hepatocytes and Kupffer cells

in vivo and in vitro Targeting of small unilamellar liposomes to the galactose

receptor in vivo Role of lipoproteins in stability and clearance of liposomes

administered to mice Antibody-directed liposomes: the development of a cell-

specific cytotoxic agent Natural antibodies against phospholipids and liposomes in

humans Liposomal drug delivery in chronic ischaemia

Liposomes in diagnostic radiology Liposomes as aids to tumour detection

Liposomes for gene transfer and expression in vivo

BOOK R E V I E W S

604th M E E T I N G , CAMBRIDGE Phosphotransferase system of Clostridium pasteurianum Regulation of hexose uptake in Chinese-hamster ovary cells Irreversible uptake of dihydrostreptomycin by Escherichia

coli K12 Epidermal growth factor receptors on porcine thyroid cell

membranes: lack of receptor antibodies in Graves' disease

Distribution of epidermal-growth-factor receptors in rat skin during embryonic development: evidence for a specific inductive interaction between a mesenchyme and an epithelium

Amidolytic activity of 7S nerve growth factor The purification by immuno-affinity chromatography of

bacterial methionyl-(human somatotropin) Characterization of mRNA sequences encoding sheep

somatotropin (growth hormone) by cloning of pituitary complementary DNA

Monoclonal antibodies that inhibit somatomedin-like activity

The specificity of binding of somatotropin (growth hor­mone) and prolactin to purified plasma membranes from rabbit liver

Plasma somatomedin activity and tri-iodothyronine and thyroxine concentrations in female rats treated with the growth promoter trenbolone acetate

Posterior pituitary peptides in human foetal and neonatal tissues

The ontogeny of (arginine)vasotocin in the human foetus and newborn

The sympathetic control of brown-fat growth in animals and humans

239

287

W . J . WHELAN 331

H . M . PATEL 333 F . H . ROERDINK, J . DIJKSTRA, H . H . SPANIER & 335 G L . SCHERPHOF G . GREGORIADIS & J . SENIOR 337

J . SENIOR & G . GREGORIADIS 339

T . D . HEATH, K . S. BRAGMAN, K . K . MATTHAY, 340 N . G . LOPEZ-STRAUBINGER & D . PAPAHADJOPOULOS

C . R . A L V I N G 342

T . N . PALMER, M . A . CALDECOURT & 344 R . O . KINGABY V . J . C A R I D E 346 G . M . BARRATT, B . E. RYMAN, K . A . CHESTER & 348 R . H . J . B E G E N T C . NICOLAU 349

351

W . J . M I T C H E L L & I . R . BOOTH 239 P. F A I K & M . J . MORGAN 240 S. N . Y O U N G & W . W . NICHOLS 240

S. ATKINSON & P. K E N D A L L - T A Y L O R 242

M . R . G R E E N & J . R . COUCHMAN 243

W . F . L O N G & F . B . WILLIAMSON 244 G . W . JACK & H . J . G I L B E R T 246

J . M . WARWICK & M . WALLIS 247

D . C WATKINS & M . WALLIS 249

C . F . LEAROYD, H . F . CADMAN & M . WALLIS 250

P. A . SINNETT-SMITH, A . N . BROOKS, 251 N . W . DUMELOW, B . G . VERNON, N . B. HAYNES & P. J . BUTTERY

A . SMITH, N . MCINTOSH & N . D . CARTER 252

N . MCINTOSH, A . SMITH & N . D . C A R T E R 253

G. MORY , D. RICQUIER, M . NECHAD, F . BOUILLAUD 254 & J . THIBAULT

COMMUNICATIONS

1984

CONTENTS vii

Is GTPase involved in the Stimulation by human chorio­gonadotropin of luteal adenylate cyclase?

Silica-released macrophage factor that stimulates protein synthesis in fibroblasts

Regulation of growth kinetics of endometrial cells in primary culture

Growth potential of endometrial cells in primary culture Low-molecular-mass tumour angiogenesis factor The partial purification of colony-stimulating factors from

human placental-conditioned medium The effect of mouse fibroblast interferon on proinsulin

biosynthesis Large-scale production and purification of Clostridium

perfringens type A enterotoxin The effect of Escherichia coli enterotoxin and methotrexate

on drug absorption Development of an inhibition Magnetic Enzyme Immuno-

Assay (MEIA) technique for determination of staphylo­coccal enterotoxin B

Effect of Clostridium botulinum toxin on neuroblastoma cells

Development of a Magnetic Enzyme ImmunoAssay (MEIA) technique for determination of anti-(staphylo-coccal enterotoxin) immunoglobulin G-type antibodies

The effect of chemical modification on the activity of heat stable enterotoxin from Escherichia coli

Effects on prostaglandin synthesis in WI-38 human lung fibroblasts following inhibition of acylation

Chloroplast genes for components of the ATP synthase complex

Chloroplast genes for components of the cytochrome b-f complex from pea

Localization of the gene for the P700-chlorophyll a protein in chloroplast DNA from pea and wheat

cDNA cloning of rabbit fatty acid synthetase

Subcloning of the Escherichia coli genes aroA (5-enol-pyruvylshikimate 3-phosphate synthase) and aroB (3-de-hydroquinate synthase)

Subcloning of the Escherichia coli shikimate dehydrogenase gene (aroE) from the transducing bacteriophage Xspcl

The mercury-resistance genes of transposon Tn501: nucleo­tide sequence of the mer operon and a possible mech­anism for mercury detoxification

Cell-free translation of the uncoupling protein of brown-fat mitochondria

Purification and expression of an Abelson-murine-leukae-mia-virus-encoded protein kinase from Escherichia coli

Investigation of the activity of yeast phosphoglycerate kinase by site-specific mutagenesis

Non-radioactive gene-specific probes The properties of immobilized horseradish peroxidase Analysis of a retrovirus-like mouse gene family Studies on a human tRNA gene Putative high-mobility-group (HMG) non-histone chromo­

somal proteins from wheat germ Restriction-endonuclease digestion of topoisomer families Coloured Computergraphic displays of subunit-subunit

interfaces of oligomeric proteins The human glutathione 5-transferases: studies on the

distribution of the GST1, GST2 and GST3 isoenzymes

G . J . M U R P H Y & D . A . STANSFIELD 255

E. K U L O N E N , M . A A L T O & M . POTILA 256

R . P. F I E L D & R . E. L E A K E 258

I . MUNIR & R . E. L E A K E 259 J . B . WEISS, C . R . H I L L & A . SCHOR 260 W . S. GILMORE 261

C . J . RHODES & K . W . T A Y L O R 262

D . REYNOLDS, H . S. TRANTER, B . J . C A P E L , 262 B . A . BARTHOLOMEW & M . F . STRINGER J . L Y N C H & M . L . LUCAS 263

P. D . P A T E L & P. A . GIBBS 264

P. NEAVES, L . F . J . WOODS, P . D . P A T E L & 265 P. A . GIBBS

P. D . PATEL, J . M . WOOD & P. A . GIBBS 266

B . R . BOOTH , E. J . W O L F F E & M . A . SOWA 268

S. A . HUNTER, S. BURSTEIN & C . SEDOR 269

A . K . H U T T L Y , C . J . H O W E , C . M . BOWMAN, 270 T . A . D Y E R & J . C . G R A Y

D . L . W I L L E Y , A . L . PHILLIPS & J . C . G R A Y 271

A . G . SMITH & J . C . G R A Y 272

I . R . CAMERON, R . D I L S , R . A . F A L L O N & 273 C . J . SKIDMORE

K . DUNCAN & J . R . COGGINS 274

I . A . ANTON & J . R . COGGINS 275

N . L . BROWN, R . D . PRIDMORE & D . C . FRITZINGER 276

F . BOUILLAUD, D . R I C Q U I E R & J . THIBAULT 277

J . G . FOULKES, J . Y . J . W A N G , N . C . ANDREWS & 277 D . BALTIMORE C . A . B . WILSON, M . F . T U I T E , M . J . DOBSON, 278 S. M . KINGSMAN, A . J . KINGSMAN, L . A . G L O V E R , N . HARDMAN, H . C . WATSON & L . A . FOTHERGILL J . L . WOODHEAD & A . D . B . M A L C O L M 279 N . SMALL, J . L . WOODHEAD & A . D . B . MALCOLM 280 A . T . CARTER, J . D . NORTON & R . J . A V E R Y 281 J . P. GODDARD, M . B I E N Z , M . SQUIRE & J . D . SMITH 282

E. L . V. MAYES & J . M . W A L K E R 283

G . S. SNOUNOU & A . D . B . MALCOLM 284 E. J . M I L N E R - W H I T E 285

R . C . STRANGE, C . G . F A U L D E R , B . A . DAVIS, 285 J . A . H . BROWN, D . A . HOPKINSON & W . COTTON

Vol. 12

vii i CONTENTS

605th M E E T I N G , S T R A T H C L Y D E

The effect of microtubule and microfilament disruption on the secretion of fucose- and mannose-containing glyco­proteins from normal and cystic-fibrosis fibroblasts

Biochemical evidence for a case of canine fucosidosis

The role of mannosyltransferase in cellulose synthesis in mung-bean hypocotyls

Changes in glucuronyltransferase activity during tissue development in pea epicotyls

The use of concanavalin A as a probe for ADP-ribosylated glycoproteins

Partial purification of UDP-N-acetyl-/?-D-glucosamine-L-asparagine sequon /?-D-glucosaminyltransferase from human serum

Location of bi- and tri-antennary Af-glycans among the heterogeneous forms of human serum transferrin: a topographical study

Incomplete blood-group substances in the metastases of gastro-intestinal tumours

The formation of membrane-bound glycoproteins by ex-plants of malignant human breast tissue

Changes in transglutaminase activity during tumour growth and metastasis

A study of the pulmonary toxicity induced by the anti-tumour compound bleomycin

Multiple antigenic determinants of the Epithelial Mem­brane Antigen

Heparin sulphates of chemically transformed BHK cells in which the transformed growth trait is temperature-dependent

Polarimetry as a technique for the study of glycosaminogly-can-metal-ion interactions

Altered water structure in mixtures of heparin and metal ions

Binding of the Helix pomatia lectin to the surfaces of normal and leukaemic lymphoid cells

Sequence analysis of dermatan sulphate oligosaccharides Ascorbate increases the sulphation of glycosaminoglycans

synthesized by human skin fibroblasts Effect of phorbol esters on ADP-ribose transferase in

cultured mouse lymphoma (LI210) cells Germination and protein ADP-ribosylation Solubilization from sheep erythrocyte membranes of the

potassium-transport-associated antigens L p , Lj and M , and the molecular size determination of the L p antigen by radiation inactivation

Isolation of a neurotensin-degrading enzyme from rat brain Enhancement of the neuritogenicity of peripheral-nervous-

system myelin proteins of P 0 and P 2 by lysophos-phatidylcholine

L-Homocysteine enhances pyridoxal 5'-phosphate-induced seizures in the rat

Thermal stability properties of immobilized creatine kinase Activation of the Ca 2 +-sensitive K + channel in erythro­

cytes at low temperature Amino acids in the human placental intervillous space Plasma amino acids in the mid-trimester human foetus An electron-paramagnetic-resonance study of ferritin and

haemosiderin Human placental cell culture

V. GAVRIAS & C. J . DANPURE 287

D . ABRAHAM, W . F . BLAKEMORE, A . D E L L , 288 M . E . H E R R T A G E , J . JONES, J . D . LITTLEWOOD, J . OATES, A . C. PALMER, R . SIDEBOTHAM & B . G . WINCHESTER

A . F . D . K E N N E D Y & C. T . BRETT 289

K . W . WALDRON & C. T . BRETT 290

L . MINSHALL & W . J . D . WHISH 291

0 . M . P . SINGH & R . D . MARSHALL 292

M . W . C HATTON & L . R . B E R R Y 293

D . A . R . SIMMONS 294

A . S. A . KASSAB, F . W . HEMMING & R . W . BLAMEY 296

R . N . BARNES, P. J . BUNGAY, B . M . E L L I O T , 297 P. L . WALTON & M . G R I F F I N M . IQBAL, B . SCANLON, L . L . SMITH & M . G R I F F I N 298

J . H . WESTWOOD, M . G . ORMEROD, K . S T E E L E & 299 M . N . MAZZINI

N . E . WOODHEAD, W . F . LONG, F . B . WILLIAMSON & 300 W . J . HARRIS

C. F . MOFFAT, D . GRANT, W . F . L O N G & 301 F . B . WILLIAMSON

D . GRANT , C. F . MOFFAT, W . F . L O N G & 302 F . B . WILLIAMSON M . J . HARDING & J . T . G A L L A G H E R 302

1. N . HAMPSON & J . T . G A L L A G H E R 303 M . EDWARD & R . F . O L I V E R 304

M . WRIGHTMAN, D . FURNISS & W . J . D . WHISH 305

N . A B E D & W . J . D . WHISH 305 C. E . SMALLEY, E . M . T U C K E R , I . SEPULVEDA & 306 J . C. E L L O R Y

J . R . MCDERMOTT 307 C. A . L O V E L I D G E , P . M I L N E R , W . A . T A Y L O R , 308 A . K . MACPHERSON & R . A . C. HUGHES

I . C. A L L E N & R . GRIFFITHS 309

J . R U D G E & G . F . BICKERSTAFF 311

A . C. H A L L & J . S. W I L L I S 312

N . MCINTOSH , C. H . R O D E C K & R . H E A T H 314 N . MCINTOSH , C. H . R O D E C K & R . H E A T H 315 M . P. W E I R , J . F . GIBSON & T . J . PETERS 316

D . M . L . MORGAN & V. J . TOOTHILL 317

1984

CONTENTS ix

Fluorescence-activated sorting of rat uterine deciduomal cells

Action of growth factors in rat uterine cells Attachment and growth of rat uterine cells in vitro Factors regulating rat uterine oestrogen-receptor activation The interaction of oestrogen receptor with oligodeoxy-

nucleotides Comparison of the activation of the rat uterine cytosol

oestrogen receptor by oestradiol and anti-oestrogens Effect of oestrogen administration in fatty acid synthetase

activity in male chick liver Formation of free and sulphated oestrogens in porcine

testicular microsomes: effects of aminoglutethimide on the pathway from 19-hydroxyandrost-4-enedione

The involvement of calcium ions in phosphatidylinositol hydrolysis in the anterior pituitary

OGlycosylation of herpes simplex virus glycoproteins carrying high-mannose glycans

K . N . M C C O N N E L L , B . D . YOUNG, J . E. O ' G R A D Y & 318 B . G R E E N R . P. F I E L D & R . E . L E A K E 319 I . MUNIR & R . E . L E A K E 320 L . MYATT, M. G . E L D E R & J . O. WHITE 321 S. M . H Y D E R , M . G . E L D E R , L . LIM & L . MYATT 322

J . O. WHITE, M . G . E L D E R & L . MYATT 323

S. COURTNEY & R . MANNING 324

R . M . A Y L I N G , C . L Y N E & D . B . G O W E R 325

J . G . BAIRD, R . J . H . WOJCIKIEWICZ, 327 P. R . M . DOBSON & B. L . BROWN F . SERAFINA-CESSI, F . DALL'OLIO & 328 G . CAMPADELLI-FIUME

C o n t e n t s Volume 12, Part 3

606th MEETING, CORK Colloquium: Molecular Aspects of Malignant Hyperthermia

and Muscular Dystrophy A biochemical abnormality found in muscle from un­

stressed malignant-hyperpyrexia-susceptible humans Skeletal-muscle mitochondria and phospholipase A 2 in

malignant hyperthermia Mitochondrial and plasma membrane changes in skeletal

muscle in the malignant hyperthermia syndrome Duchenne muscular dystrophy Problems in the prenatal diagnosis of Duchenne muscular

dystrophy X-Chromosome-coded antigens in Duchenne muscular

dystrophy X-Chromosome-specific polymorphisms in Duchenne mus­

cular dystrophy: clinical applications

Symposium: Transport of Proteins, Ions and Electrons Through Mitochondrial Membranes

Import of mitochondrial proteins Transport of nuclear-coded proteins into mitochondria Transport and processing of the precursors of mitochondrial

carbamoyl phosphate synthetase I and ornithine transcarbamoylase

Large amplitude protein movement. What functions?

Transport of mature proteins into isolated mitochondria: a model system to investigate mitochondrial biogenesis

Energy transduction, ion transport and protonmotive force: are they linked?

Proton translocation coupled to mitochondrial electron transport

Proton and calcium circuits across the mitochondrial inner membrane

Characteristics of the uncoupling protein from brown-fat mitochondria

A possible physiological role of the Na + /Ca 2 + exchange mechanism of brown-fat mitochondria in the mediation of a,-adrenergic signals

F. R . E L L I S , P. J . HALSALL, P . A L L A M & E . H A Y 357

K . S. CHEAH 358

J . J . A . HEFFRON 360

S. V. PERRY 362

D. C WATTS 366

F. S. WALSH 368

T. O ' B R I E N 371

M. A . HARMEY & W . NEUPERT 373 G. A . R E I D 374 P. P. COHEN 377

A. WAKSMAN, G. C R E M E L , P. HUBERT, C . MUTET & 378 C . B U R G E N S. PASSARELLA, E. MARRA, S. DOONAN, C . SACCONE & 381 E . QUAGLIARIELLO

M . L . CAMPO, C . - J . ZHANG & H . TEDESCHI 384

A. L . LEHNINGER 386

D. G. NICHOLLS, R . SNELLING & E . R I A L 388

M . KLINGENBERG 390

J . NEDERGAARD, E . CONNOLLY, E . NÄNBERG & 393 N . MOHELL

Vol. 12

X CONTENTS

Electron flow in membranes Some implications of fixed-charge formation during elec­

tron-transport-chain activity A structural basis for mosaic protonic energy coupling

Lateral diffusion, collision and efficiency of oxidation-reduction components in mitochondrial electron transport

Effects of physical exercise and/or vitamin E on tissue oxidative metabolism

Carboxyl groups and the proton pump of bacteriorhodopsin

Colloquium: Current Problems in the Understanding of Protonmotive Systems

Properties and physiology of energy-coupled mutants of Escherichia coli

Bioenergetic problems of alkalophilic bacteria Proton-transfer pathways during bacterial electron-trans­

port phosphorylation 'Cross-talk' between redox- and ATP-driven H + pumps Analysis of relationships between the protonmotive force

and rates and extents of ATP synthesis

Colloquium: Structures and Catalysis by Aspartate Amino­transferase Isoenzymes

On the catalytic factors involved in the mechanism of aspartate aminotransferase: Chairman's remarks

Primary structures of aspartate aminotransferases Three-dimensional structure of mitochondrial aspartate

aminotransferase and some functional derivatives: impli­cations for its mode of action

Correlation of structure and catalysis by aspartate amino­transferase isoenzymes

Comparison of aspartate aminotransferase with other aminotransferases by absorption-spectrum analysis

COMMUNICATIONS

605th MEETING, S T R A T H C L Y D E Colloquium: Genetic Aspects of Glycoproteins Genetic aspects of glycoproteins: Chairman's introduction Model studies on N-glycosylation of proteins The role of three-dimensional structure in the control of TV-

linked oligosaccharide biosynthesis Studies of membrane glycoproteins in the rough endoplas­

mic reticulum Role of a-D-mannosidases in the biosynthesis and catabo-

lism of glycoproteins Exchange of lysosomal enzymes between cells Non-specific adsorptive pinocytosis Intracellular turnover and secretion of lysosomal enzymes

Colloquium: Glycoconjugates and Tumour-Cell Surfaces Regulation of cell-surface structures in malignancy, differ­

entiation and proliferation A variant of Tamm-Horsfall glycoprotein produced by

transformed (BHK 21 /CI3) cells: implications in the biosynthesis of carbohydrates moieties

Surface glycoproteins in chronic lymphocytic leukaemias The structure of the Ca-antigen

Cell interactions: some critical reappraisals Heparan sulphate alterations in tumour cells

R . J . P. WILLIAMS 396 F . H . MALPRESS 399

K . V A N DAM, H . WOELDERS, A . C O L E N & 401 H . V . WESTERHOFF C R . HACKENBROCK, S. G U P T E , E . - S . W U & 402 K . JACOBSON

A . T. QUINTANILHA 403

J . M . H E R Z &-L. P A C K E R 405

I . R . BOOTH, R . G . K R O L L , M . J . FINDLAY, 409 L. M . D . STEWART & G . C . ROWLAND

A . A . GUFFANTI & T. A . K R U L W I C H 411

D . B . K E L L & G . D . HITCHENS 413

G . F . AZZONE, V . PETRONILLI & M . ZORATTI 414 S. J . FERGUSON & D . PARSONAGE 416

C . A . VERNON 420

F . BOSSA, D . BARRA & S. DOONAN 421 J . N. JANSONIUS, G . E I C H E L E , G . C . F O R D , 424 J . F . K I R S C H , D . PICOT, C . T H A L L E R , M . G . VINCENT, H . G E H R I N G & P . CHRISTEN P. CHRISTEN, H . G E H R I N G , E . SANDMEIER, 427 H . KIRSTEN, K . PFISTER & J . N. JANSONIUS R. A . JOHN, P . H . MORGAN & L . J . F O W L E R 430

433

R. D . MARSHALL 513 E . BAUSE 514 J . P . CARVER 517

P. H . ATKINSON & A . K . K A B C E N E L L 519

B . WINCHESTER 522

M . F . D E A N & S. DIMENT 524 J . B . L L O Y D & K . E . WILLIAMS 527 W . JESSUP, J . L . BODMER, R. T . D E A N , 529 V . A . GREENAWAY & P. L E O N I

M . F . GREAVES 532

R. D . MARSHALL 533

S. K . SMITH & A . H . MADDY 535 G . WISEMAN, M . E . BRAMWELL, 537 V . P . BHAVANANDAN & H . HARRIS A . S. G . CURTIS & J . V . FORRESTER 538 D . J . WINTERBOURNE & Z . K H A N 540

1984

CONTENTS xi

Proteoglycans in cellular differentiation and neoplasia Carbohydrate differentiation and cancer-associated anti­

gens detected by monoclonal antibodies Monoclonal antibodies reveal saccharide structures of

glycoproteins and glycolipids as differentiation and tumour-associated antigens"

Surface glycoprotein changes during normal and malignant haematopoietic differentiation

Mutants, revertants and variants of metastasis

B O O K R E V I E W S

J . T. G A L L A G H E R & I . N . HAMPSON 541 J . L. MAGNANI 543

T. F E I Z I 545

C. G . GAHMBERG , L. C. ANDERSSON, K . K . K A R H I & 549 H . RODT M . M . BURGER, J . FINNE & J . - P . PRIEELS 553

557

Purification of NAD +-dependent dehydrogenases by affin­ity precipitation with adipo-Ar2,Af2'-dihydrazidobis-(Af6-carboxymethyl-NAD +)(bis-NAD +)

Mitochondrial transplantation in hepatocytes and HTC cells: studies of subsequent protein destruction

Stimulation by feeder layers of human tumour-cell colony formation in agar

Inhibition of fibroblast contamination in cultures of human epithelial cells

The non-identity of protein phosphatase deinhibitor and protein kinase inhibitor

The effects of pulsed electromagnetic fields on membrane transport, protein and ATP synthesis in rat skin

Differential gene expression in rapidly dividing cells of Schizosaccharomyces pombe

Magnesium and control of mitochondrial morphology in fission yeast

Multiple forms of calf prochymosin and chymosin

Changes in the surface of mouse spermatozoa during their passage through the epididymis

Immunofluorescence studies on spermatozoa from the mouse epididymis

Cytosolic and mitochondrial fumarases Import of aspartate aminotransferase into mitochondria

Comparative studies of the primary structures of aspartate aminotransferase

Biliary excretion of [14C]androstenedione metabolites in control and clofibrate-treated male rats

The effects of surgery and hepatic dysfunction on alanine metabolism in man

Insulin suppression is the primary mediator of changes in circulating metabolites during surgery in man

The effect of inhibitors of ADP-ribose transferase on the concentration of (ADP-ribose)„ in vitro

Effect of dimethyl sulphate on ADP-ribosylation in mouse L1210 cells

Loss of nicotinamide from cells treated with dimethyl sulphate

Monoclonal-antibody-mediated delivery of deacetylcolchi-cine to human peripheral blood neutrophils

Mitochondrial functions in mutants of Drosophila melanogaster

The antigenic region of the coat protein of the O subtypes of foot and mouth disease virus

Effect of allopurinol (4-hydroxypyrazolo [3,4-*/]pyrimidine on purine metabolism in rat skeletal muscle

Vol. 12

R . BEATTIE, L . D . GRAHAM, T . O . G R I F F I N & 433 K . F . TIPTON

S. M . RUSSELL, P. J . EVANS & R . J . M A Y E R 434

V. MCMANUS & M . C L Y N E S 435

S. M C D O N N E L L , M . MORI ARTY & M . C L Y N E S 435

E . WAELKENS, J . GORIS, D . A . WALSH & 436 W . M E R L E V E D E P. H . DELPORT, N . C H E N G , J . C . M U L I E R , 437 W . M . SANSEN & W . DE L O E C K E R

G . M . W A L K E R & B . KRAMHOFT 438

G . M . W A L K E R & A . BIRCH-ANDERSEN 439

W . J . DONNELLY, D . M . O'CALLAGHAN, 440 D . P . C A R R O L L , D . J . M C C O N N E L L & F . GANNON K . M . D E V I N E & J . C A R R O L L 441

G . J . P. MURPHY & J . C A R R O L L 442

M . C . O ' H A R E & S. DOONAN 443 K . M . C . O'DONOVAN, S. DOONAN, E . MARRA & 444 S. PASSARELLA F . MARTINI, S. ANGELACCIO, D . BARRA, F . BOSSA & 445 S. DOONAN M . E . BEARY & V. O'SHEA 446

G . M . H A L L , M . FLANNIGAN, J . L . PATERSON & 447 S. M . SAPSED G . M . H A L L , E . S. WALSH, J . L . PATERSON & 448 K . MASHITER

W . H . M U L L E N , L . MINSHALL & W . J . D . WHISH 449

W . H . M U L L E N & W . J . D . WHISH 449

S. AL-MUHTASEB & W . J . D . WHISH 451

T . G . COTTER, T . D . F E C Y C Z & K . O ' M A L L E Y 452

N . O ' B Y R N E - R I N G , H . QAZZAZ, A . BEHAN & 453 E . J . D U K E F . BROWN, A . C A R R O L L , B . E . C L A R K E , 454 B . H . NICHOLSON & D . J . ROWLANDS J . M . M U R P H Y & E . R . T U L L Y 455

xii

The puzzle of high phosphorylation potential and low protonmotive force generated by oxidative phosphoryla­tion in Paracoccus denithficans membrane vesicles in the presence of nitrate

Complementation studies in fibroblast cultures from pa­tients with abnormal cystathionine ß-synthase activity (homocystinuria)

Prenatal diagnosis of non-ketotic hyperglycinaemia The analysis, metabolism and encapsulation of coumarin Purification of pig gastric-mucosal 7V-acetyl-/?-D-

glucosaminidase Suppressor T-lymphocytes in malignancy

Ascorbic acid content of plasma and cellular components of blood

Effect of varied membrane protein density on the lateral diffusion of lipids in the mitochondrial inner membrane

The pyruvate-oxidation system of the lipoamide dehydro-genase-containing anaerobe Peptococcus glycinophilus

Dimethyl sulphoxide inhibits electron transfer to haem a3

from haem a and its associated copper in cytochrome c oxidase

Hydrogen peroxide as a substrate for cytochrome c oxidase Investigation of the nature of inhibition of the mitochon­

drial Fi -ATPase by 4-chloro-7-nitrobenzofurazan The effect of pH on the slow kinetic transients of

arylsulphatase A Purification and structural analysis of aromatic-amino-

acid-accepting tRNA species from the green alga Scenedesmus obliquus

The effect of N a + on growth and intracellular pH of a facultative alkalophile

Effect of acetylcholine and tetraethylammonium on the contractile response produced in the rat ileum

Does glycerol facilitate neuromuscular transmission? Multiple forms of calmodulin on sodium dodecyl sulphate/

polyacrylamide-gel electrophoresis Purification of the mitochondrial phosphate-hydroxyl ion

antiporter from rat liver Organization and distribution of carbohydrate on mito­

chondrial membranes Prostaglandin synthase activity in tissues from guinea pigs

fed fatty acid- and aspirin-supplemented diets Relationships between forms of deoxyribonuclease I from

several mammals An inhibited form of deoxyribonuclease lb in extracts of

Aspergillus nidulans Relationship between products and mechanism of action of

deoxyribonuclease lb of Aspergillus nidulans Calcium uptake and retention by skeletal-muscle

mitochondria Effects of denervation on calcium uptake and release

pathways of rabbit skeletal-muscle mitochondria Second-derivative fluorescence spectroscopy in the study of

membrane protein conformational changes Possible biochemical basis for bilirubin neurotoxicity Calcium fluxes in synaptosomes from rat cerebral cortex Comparison of the degree of non-biospecific binding of

1 2 5I-labelled insulin to Sepharose CL-6B conjugates prepared with different activating agents

A strategy for the cloning of the human oestrogen-receptor gene: optimization of an immunodetection system for use in the screening of a cDNA library

CONTENTS

D . PARSONAGE & S. J . FERGUSON 456

J . S. Fox, N . A . J . CARSON & M . H . R . L E W I S 457

J . S. Fox, N . A . J . CARSON & M . H . R . L E W I S 458 E . MORAN, R . O ' K E N N E D Y & R . D . THORNES 459

R . D E V E R Y , P. B . COLLINS, A . H . JOHNSON & 460 G . WATSON B. M . HANNIGAN, A . H . JOHNSON, P. B . COLLINS, 461 M . MORIARTY & P. K E E L I N G A . M . B . K E A T I N G E , B . M . HANNIGAN, 462 A . H . JOHNSON, P. B . COLLINS, M . MORIARTY & P. K E E L I N G B . CHAZOTTE, E . - S . W U & C . R . HACKENBROCK 463

S. G . MAYHEW, G . DOHERTY, D . M C G R A T H & 464 C . H . WILLIAMS, JR. N . S. DAHABRAH & J . M . WRIGGLESWORTH 465

J . M . WRIGGLESWORTH, J . E L S D E N & H . BAUM 466 R . SUTTON & S. J . FERGUSON 467

B . M . B U T L E R & T . J . MANTLE 468

G . A . G R E E N & D . S. JONES 468

D . M C L A G G A N , M . J . S E L W Y N , B . M . L U N D & 470 A . P . DAWSON F. A . W A L I 471

F. A . W A L I 472 D . C WILLIAMS, C . O'RIORDAN, R . E . BEATTIE & 472 C . O ' N E I L L G . M . G I B B , G . P. R E I D & J . G . LINDSAY 474

J . G . LINDSAY, G . P. R E I D & W . DARLINGTON 475

C . HADJIAGAPIOU, C . TRITSCHLER & 476 M . G . HARRINGTON

C . SMYTHE & F. G . WINDER 477

F. G . WINDER & D . SHEILS 478

F. G . WINDER & M . SHIKARA 479

A . P . ALLSHIRE & J . J . A . HEFFRON 480

L . A . B U R K E & J . J . A . HEFFRON 481

J . J . BIRMINGHAM & J . J . A . HEFFRON 482

A . O'CALLAGHAN & P. F. DUGGAN 483

M . C A P L I C E & P. F. D U G G A N 484

J . G . M A X W E L L & G . B . IRVINE 485

P. G I L N A , D. COLLINS, G . L. G R E E N E & F. GANNON 486

1984

CONTENTS xii i

Towards the cloning of the calf prochymosin gene

Replacement of anticodon-loop nucleotides to produce functional tRNAs

Molecular studies on the DNA-repair genes of the cyanobacterium Gloeocapsa alpicola

Expression of phosphoglucose isomerase and glucose 6-phosphate dehydrogenase from Leuconostoc mesenter-oides in Escherichia coli

Characterization of complex genetic rearrangements in recombinant plasmids

Host selection of Rhizobium trifolii on Trifolium repens (clover)

Generation of multiple-host Rhizobium strains by plasmid transfer

An improved spectrophotometric assay for monoamine oxidase in mitochondria

Characterization of mRNA from mumps-virus-infected cells

Molecular cloning of bovine enterovirus

Purification and characterization of canine-distemper-virus mRNA

Neurovirulence of canine-distemper virus for hamsters The effect of digitonin on the fluorescence anisotropy

depolarization of cholesterol-containing liposomes Cloning and identification of promoters from temperate

phage 0105 in Bacillus subtilis, using a versatile 'promoter-probe' vector

An electron paramagnetic resonance study of Escherichia coli fumarate reductase: its iron-sulphur centres and their organization

The iron-sulphur centres of the Escherichia coli electron transport chain: changes in response to aerobic growth on different carbon sources

A kinetic and electron spin resonance study of the blue copper protein rusticyanin from Thiobacillus ferro-oxidans

The physiology of unc mutants of Escherichia coli D-Alanine transport in Escherichia coli Energy coupling to K + transport via the Trk system of

Escherichia coli Direct interactions between electron transfer chains and

solute transport systems in bacteria Kinetic studies on the ATP synthesis reaction in liposomes

containing bacteriorhodopsin and ATPase-complex Direct interaction between ATP synthase and the respir­

atory chain in beef heart submitochondrial particles Free and total tri-iodothyronine and thyroxine in malnour­

ished Jamaican infants

T H E F I F T H THUDICHUM L E C T U R E The structure and function of cholinergic synaptic vesicles

607th MEETING, LONDON Colloquium: Advances in the Biochemistry and Genetics of

Antibiotic-Producing Organisms Genetic studies in micro-organisms producing 0-lactam

antibiotics

D . J . M C C O N N E L L , D . HUGHES, Y . - F . C H E N , 487 D . P. C A R R O L L , W . J . D O N N E L L Y , J . F . OLLINGTON, D . QUINN, T . BARRY & F . GANNON A . G . B R U C E , J . F . ATKINS, N . W I L L S , L . BARE, 488 O . U H L E N B E C K & R . F . G E S T E L A N D D . N U T T A L L , C . GEOGHEGAN & J . A . HOUGHTON 488

T . SCHWARZ, N . B . M U R P H Y & D . M C C O N N E L L 489

N . B . MURPHY, T . SCHWARZ & D . M C C O N N E L L 490

J . N E I L A N , D . N . D O W L I N G & L . K . DUNICAN 492

L . K . DUNICAN, D . N . D O W L I N G , J . N E I L A N & 492 M . O ' C O N N E L L

C . H . WILLIAMS 493

J . A . CURRAN, E . M . H O E Y & B . K . RIMA 494

E . M . H O E Y , R . O . CAMPBELL, J . A . P . E A R L E & 495 S. J . MARTIN

S. E . H . RUSSELL, E . M . H O E Y , B . K . RIMA & 496 S. J . MARTIN S. L . COSBY, C . LYONS & S. J . MARTIN 497 P. G R E E R & N . M . R Y A N 498

P. DHAESE, C . HUSSEY & M . V A N MONTAGU 499

D . SIMPKIN & W . J . I N G L E D E W 500

M . C . K I R B Y & W . J . I N G L E D E W 501

C . A . L E W I S , A . G . LAPPIN & W . J . INGLEDEW 503

R . G . K R O L L , C . V . SALMOND & I . R . BOOTH 504 G . C . ROWLAND & I . R . BOOTH 505 L . M . D . STEWART, E . P . B A K K E R & I . R . BOOTH 506

K . J . H E L L I N G W E R F , M . G . L . E L F E R I N K & 507 W . N . KONINGS

R . L . V A N DER BEND, J . PETERSEN & J . A . BERDEN 508

M . A . H E R W E U E R , J . A . B E R D E N & A . K E M P 509

H . M . PAYNE ROBINSON, H . BETTON & 511 A . A . JACKSON

V. P. WHITTAKER 561

G. H O L T , M. W . A D L A R D , E. LISBOA, 577 M. E. ROGERS, S. D. R O G E R S , G. SAUNDERS & T. M. SMITH

C o n t e n t s Volume 12, Part 4

Vol. 12

xiv CONTENTS

Aspects of the biosynthesis of ß-lactam antibiotics ß-Lactamases and their inhibition Dissecting the Streptomyces genome

Recombinant DNA methods for the Oxytetracycline pro­ducer Streptomyces rimosus

Optimization of streptomycete strains producing polyether and macrolide antibiotics

Colloquium: Mucin-Type Glycoproteins Tumour-associated and differentiation antigens on the

carbohydrate moieties of mucin-type glycoproteins

The human blood-group-Sda determinant: a terminal non-reducing carbohydrate structure in AMinked and mucin-type glycoproteins

Carbohydrate chains from human bronchial mucus glyco­proteins: a wide spectrum of oligosaccharide structure

Structural analysis of the carbohydrate chains of mucin-type glycoproteins by high-resolution ^-n.m.r . spectroscopy

Mucin sialidase in the rat large intestine The effect of mild alkali and alkaline borohydride on the

carbohydrate and peptide moieties of fetuin Effect of alkalis on N-glycosidic linkages of glycoproteins Structure and gel formation in pig gastric mucus Is the macromolecular architecture of cervical, respiratory

and gastric mucins the same? Confirmation of human mucus glycoproteins observed by

electron microscopy Studies on the molecular weight distributions of two mucins

Colloquium: Lasers in Biochemistry Light scattering and correlation measurement Low-angle laser light scattering from surfactant solubilized

biological macromolecules The measurement of motility in micro-organisms and its

biochemical significance Picosecond spectroscopy: applications in biochemistry.

Part I : techniques Picosecond spectroscopy: applications in biochemistry.

Part I I : applications Laser Doppler microscopy

COMMUNICATIONS

606th MEETING, CORK Colloquium: Applications of Gene Cloning and Monoclonal

Antibodies in the Study and Production of Viral Proteins Alternative vaccines Hepatitis B virus (By title only) Chemical basis of antigenic variation in foot-and-mouth-

disease virus The use of monoclonal antibodies for selection of a low-

abundance mRNA: p53 Organization of poliovirus genome and the sites for

proteolytic processing (By title only) Bovine enteroviruses

BIOCHEMICAL R E V I E W Models of the interactions between membranes and

intracellular protein structures

BOOK R E V I E W S

E . P. ABRAHAM 580 G . W . Ross 582 K . CHATER, M . BIBB, C BRUTON, D . HOPWOOD, 584 G . JANSSEN, F . MALPARTIDA & C . SMITH P. M . RHODES, I . S. HUNTER, E . J . F R I E N D & 586 M . W A R R E N Z . VANEK, S. POSPISIL, P . SEDMERA, P. T I C H Y , 587 T . REZANKA & V . KRUMPHANZL

T . F E I Z I , H . C . GOOI , R. A . CHILDS, J . K . PICARD, 591 K . UEMURA, L . M . LOOMES, S. J . THORPE & E . F . HOUNSELL A . S. R. DONALD, A . D . YATES, C . P. C . SOH, 596 W . T . J . MORGAN & W . M . WATKINS

G . LAMBLIN, M . LHERMITTE, A . K L E I N , P. ROUSSEL, 599 H . VAN H A L B E E K & J . F . G . VLIEGENTHART H . VAN H A L B E E K 601

A . P . C O R F I E L D & J . R. CLAMP 605 E . F . HOUNSELL, N . J . PICKERING, M . S. STOLL, 607 A . M . LAWSON & T . F E I Z I H . DEBRAY, G . STRECKER & J . MONTREUIL 611 A . A L L E N , D . A . HUTTON, D . MANTLE & R. H . PAIN 612 I . CARLSTEDT & J . K . SHEEHAN 615

P. ROUSSEL, G . LAMBLIN, N . HOUDRET, 617 M . LHERMITTE & H . S. SLAYTER J . M . C R E E T H & B . COOPER 618

P. JOHNSON 623 M . N . JONES & P. J . W . M I D G L E Y 625

R. A . K L E I N 627

T . A . M . DOUST, D . PHILLIPS & G . PORTER 630

T . A . M . DOUST, D . PHILLIPS & G . PORTER 633

R. P. C . JOHNSON 635

S. J . MARTIN 703 K . MURRAY 705 F . BROWN 705

S. BENCHIMOL, G . AMTLASHEWSKI & L. CRAWFORD 708

C . W . ANDERSON, A . J . DORNER , R. HANECAK, 711 B . L. SEMLER & E. WIMMER

E. M . H O E Y 711

P. S. AGUTTER & K . E. S U C K L I N G 713

719

1984

CONTENTS xv

COMMUNICATIONS

607th MEETING, LONDON Identification of the amidase regulator gene sequence of

Pseudomonas aeruginosa High-performance liquid-chromatographic determination

of ^-lactam antibiotics using pre-column and post-column derivatization techniques

The effects of chemicals in the presence of cellophane on X-ray-induced point mutation and gene conversion in Aspergillus nidulans

Use of [3H]tetrahydrocerulenin to assay condensing enzyme activity in Streptomyces erythreus

'Restriction-deficient' mutants of industrial Streptomyces Construction and use of a bifunctional streptomycete

cosmid Cloning DNA from Penicillium chrysogenum D N A repair and mutagenesis in Penicillium chrysogenum Gel-forming interactions in pig gastric mucous glycoprotein Observation of the adherent mucus gel on the rat

gastroduodenal mucosa in situ Studies on pig and sheep salivary mucins Preliminary characterization of mucous glycoprotein com­

ponent of rabbit ocular mucus Control of secretion of mucin-type glycoproteins from

human and rat submandibular acini Carbohydrate antigens on glycoproteins of the neoplastic

and uninvolved mucosae of patients with carcinoma of the stomach and colon

Structural analysis of cell-free glycopeptides which bind to wheat germ agglutinin

Purification and properties of acetyl-CoA: glucosamine 6-phosphate N-acetyltransferase from rat liver

The structure of the major oligosaccharide unit of bovine testicular hyaluronidase

The regulation of androgen-receptor turnover in human genital skin fibroblasts by 5a-dihydrotestosterone

Structures and ligand-binding properties of human serum albumins

Modification of the age-dependent increase of plasma fibronectin in cancer patients

Studies on a human transferrin variant A low-molecular-weight iron-binding fragment from duck

ovotransferrin Monoclonal antibodies against muscle-cell proteins Human uroporphyrinogen decarboxylase. Do tissue-

specific isoenzymes exist? The use of immunological methods to investigate evolution­

ary relationships between hexokinase isoenzymes Immunohistochemical localization of hexokinase isoen­

zymes in rat tissues An immunoradiometric assay specific for the MM-dimer of

creatine kinase, with the use of monoclonal antibodies Phosphate distribution in mammalian epidermal keratin

proteins Microheterogeneity in a cytochrome P-450 multigene

family Biochemical analyses of human class I I histocompatibility

(HLA-D region) antigen-associated invariant poly­peptides

D . COUSENS & R . D R E W 639

M . E . ROGERS, M . W . ADLARD, G . SAUNDERS & 640 G . H O L T

C . N . I G W E & P. COHN 641

G . ROBERTS & P. F . LEADLAY 642

I . S. HUNTER & E . J . F R I E N D 643 A. E . CHAMBERS & I . S. HUNTER 644

T . M . SMITH & G . H O L T 645 S. D . ROGERS & G . H O L T 646 A. E . B E L L , A. A L L E N , E . MORRIS & 648 S. ROSS-MURPHY A. A L L E N , A. GARNER, D . A. HUTTON & 649 S. M C Q U E E N L . SELLERS & A. A L L E N 650 R . KAURA & J . M . T I F F A N Y 651

M . A. MCPHERSON & R . L . DORMER 652

J . K . PICARD & T . F E I Z I 653

J . T . G A L L A G H E R , A. MORRIS & M . D E X T E R 655

A. P. C O R F I E L D , D . T . MORTIMER & 656 P. J . WlNTERBURN J . - C . MICHALSKI , A. H . OLAVESEN, 657 P. J . WlNTERBURN, D . J . POPE & G . STRECKER D . R I N G & M . B . HODGINS 658

H . N . Au , S. BRAND, D . W. HUTCHINSON & 659 P. MATEJTSCHUK J . LABAT-ROBERT, J . -P . POTAZMAN & L . ROBERT 660

R . W. EVANS , A. BOMFORD, A. D . C L A R K , 661 R . C . GARRATT , A. D . MADDEN & S. P. Y O U N G R . W. EVANS & A. D . MADDEN 661

N . T H I MAN, L . P. H E A D & G . E . MORRIS 662 G . H . E L D E R & A. J . URQUHART 663

G . M . LAWRENCE & I . P. T R A Y E R 664

G . M . LAWRENCE , I . P. T R A Y E R & D . G . W A L K E R 665

G . E . MORRIS & L . P. HEAD 666

N . F . COOPER, P. T . BLADON, E . J . WOOD & 667 W. J . C U N L I F F E A. ASHWORTH, E . SHEPHARD, B . RABIN & 669 I . PHILLIPS C . E . R U D D , J . G . BODMER, W. F . BODMER & 670 M . J . CRUMPTON

Vol. 12

xvi CONTENTS

The use of synthetic oligonucleotides in the detection of the Z variant of a!-antitrypsin (a!-AT)

Analysis of plasma protein variants by i.e.f./p.a. (isoelectric focusing in Polyacrylamide gels) and immunoblotting techniques

Increased biosynthesis of dermal fibronectin in experi­mental and human diabetes

Paracetamol toxicity in isolated rat hepatocytes Heterogeneous distribution of phase I xenobiotic metabo­

lism in subpopulations of isolated hepatocytes Enterohepatic circulation of benzo[a]pyrene-4,5-oxide in

the rat Relationship of ricin and modeccin hepatotoxicity to

accumulation rates by parenchymal and non-parenchy-mal liver cells

An injurious effect of chlorpromazine in the murine SI80 sarcoma (var. CB) and its relevance to cancer treatment

Cryosensitization and cryoprotection of hepatic micro­somal membranes

Anthraquinone free-radical formation by mouse liver subcellular fractions

Metabolic evidence for the presence of different forms of cytochrome P-450 in human liver

Effect of cytochrome P-450 inducers on the efficacy and nephrotoxicity of cyclosporin A

Denaturation of hepatic microsomal cytochrome P-450 by non-steroidal anti-inflammatory drugs in vitro

Ethanol induces an aniline hydroxylase in chick embryo liver without inducing cytochrome P-450

2-Acetamidofluorene as an inducer of cytochrome P-450 in the chick embryo

Inhibition of hepatic and skeletal muscle carnitine palmi­toyltransferase I by 2[5(4-chlorophenyl)pentyl-oxirane-2-carbonyl-CoA

Hydrolysis of l-0-alkyl-2-acetyl-sn-glyceiyl-3-phosphoryl-choline (AGEPC) by mouse serum

Iodination of the co-side of a thromboxane-receptor antago­nist for radioligand binding

Inhibition of glutamate binding by trifluoperazine and calmidazolium

Low concentrations of glucose precipitate a rapid dephos-phorylation of ATP in ram spermatozoa exposed to ot-chlorohydrin

Simian-virus-40 D N A transfection of synchronized CV-1 cells

Magnetic D N A Chromatographic resolution of nucleic acids: application to

organisms of industrial importance Doubly resistant variants of hypoxanthine: guanine phos-

phoribosyltransferase in Chinese-hamster cells Responses of Chinese-hamster and human foetal lung cells

to a-particle irradiation Control of the initiation of protein synthesis in CHO cells

(tsHi) with a temperature-sensitive leucyl-tRNA synthetase

Processing and disulphide-bond formation in proteins biosynthesized from isolated human pancreatic mRNA

An analysis of the changes in rat hepatocyte intermediate filaments during primary culture

Reduced rates of muscle protein synthesis during tail-vein infusion of rats

N . K A L S H E K E R , G . L . WATKINS, A . F . MARKHAM, 671 D . C H I S W E L L , S. E . HUMPHRIES & R . WILLIAMSON M . D A L Y AND F . HALLINAN 672

J . LABAT-ROBERT, L . PHAN THANH, 673 M . L E U T E N E G G E R & L . ROBERT S. FAIRHURST & A . A . HORTON 675 I . G . SUMNER, R . B . FREEDMAN & A . LODOLA 676

T . R . D . ELMHIRST, J . K . CHIPMAN, P. C . HIROM & 677 P. MlLLBURN D . N . S K I L L E T E R & F . STIRPE 678

G . R . N . JONES & M . J . N . FROHN 679

D . BROWN & T . HALLINAN 680

M . A . OLDCORNE, J . R . BROWN & L . H . PATTERSON 681

S. THOMPSON, J . C . P E T R I E , J . ENGESET, 682 C . R . ELCOMBE, R . T . M A Y E R , C . V O N BAHR & M . D . B U R K E C . CUNNINGHAM, P. H . WHITING, J . G . SIMPSON, 684 D . N . W H E A T L E Y & M . D . B U R K E M . FALZON, J . H O G G , A . S. MILTON & 685 M . D . B U R K E F . BURNET & N . D A R B Y 686

N . DARBY, F . BURNET & A . LODOLA 687

K . BARTLETT, H . S. A . SHERRATT & 688 D . M . TURNBALL

C . VAKIRTZI-LEMONIAS 689

P. V . HALUSHKA, D . R . KNAPP, I . A . B L A I R & 690 J . MACDERMOT

M . E . BARDLSEY & P . J . ROBERTS 690

W . C . L . FORD & A . HARRISON 691

A . J . STRAIN, W . A . H . W A L L A C E & A . H . W Y L L I E 692

J . A . LANGDALE & A . D . B . MALCOLM 693 G . SAUNDERS, M . E . ROGERS , M . W . A D L A R D & 694 G . H O L T

R . J . CHAMBERS & P. C O H N 695

T . M I N , P . C O H N & J . A . SIMMONS 696

S. A . AUSTIN , M . J . CLEMENS & J . W . P O L L A R D 696

M . A . KADERBHAI, J . HERMON-TAYLOR & 697 B . M . AUSTEN

C . M . ALEXANDER, A . LODOLA & K . G U L L 699

V . R . P R E E D Y & P . J . G A R L I C K 700

1984

CONTENTS xvii

C o n t e n t s Volume 12, Part 5

E L E V E N T H J U B I L E E L E C T U R E The discovery and the biological role of fructose 2,6-

bisphosphate

607th M E E T I N G , LONDON Colloquium: Effector Functions of the Constant Region of

Immunoglobulin Molecules Isotype switching in myeloma and hybridoma cells com­

pared with LPS blasts Antigenicity and effector functions of human immunoglobu­

lin G l proteins having Cyl or Cy3 deletions CI activation by immunoglobulin and immunoglobulin

antibodies Fc receptors on lymphocytes and K cells Immunoglobulin and soluble immune complex binding to

phagocyte Fc receptors The monocyte binding domain(s) on human immunoglobu­

lin G Isotope specificity in the binding of mouse immunoglobu­

lins to brush borders isolated from the neonatal mouse small intestine

Use of synthetic peptides with immunoglobulin-heavy-chain sequences in the delination of Fc effector function

The relationship between the immune system and mucus in the protection of mucous membranes

Colloquium: Phosphorylation of Membrane Proteins Tyrosine protein kinases, viral transformation and the

control of cell proliferation Stimulation of tyrosine phosphorylation by platelet-derived

growth factor The insulin receptor-kinase complex: an integrated system

for transmembrane hormone signalling Does insulin exert certain of its actions through a distinct

species of guanine nucleotide regulatory protein? Protein kinases and insulin action in fat cells

Thylakoid protein phosphorylation: in vitro and in vivo Protein phosphorylation and optimal production of ATP in

photosynthesis Control of excitation energy distribution in photosynthetic

systems in vivo

COMMUNICATIONS

BOOK R E V I E W S

Recovery of polymorphonuclear leucocytes from comple­ment attack

Role of complement receptor CR1 in the breakdown of soluble and zymosan-bound C3b

Is the stepwise methylation of phosphatidylethanolamine relevant to the release of histamine from the mast cell?

Transiently phosphorylated Mr-70000 protein of rat mam­mary-gland Golgi-vesicle membrane is not an intermedi­ate in casein phosphorylation

The possible existence of phosphoproteins as complexes on the synaptic plasma membrane

H . G. HERS 729

A . RADBRUCH, F . SABLITZKY & K . RAJEWSKY 737

R . JEFFERIS, M . I . N I K JAAFAR, R . M C A D A M & 737 M . W A L K E R N . C . HUGHES-JONES, A . FEINSTEIN, 738 N . E . RICHARDSON, B . D . G O R I C K & J . C . HOWARD J . G E R G E L Y , M . SANDOR, G . SARMAY & F . U H E R 739 R . G . Q. L E S L I E 743

J . M . WOOF & D . R . BURTON 746

N . M . MACKENZIE & K . D . K E E L E R 747

D . R . STANWORTH 747

J . R . CLAMP 754

T . HUNTER, K . L. G O U L D & J . A . COOPER 757

B . E K , L. RÖNNSTRAND & C . - H . H E L D I N 759

E . VAN OBBERGHEN, H . GAZZANO, A . KOWALSKI, 762 M . FEHLMANN, B . ROSSI & G . PONZIO

M . D . HOUSLAY, A . V . W A L L A C E , M . E . COOPER, 766 N . J . PYNE, S. R . WILSON & C . M . HEYWORTH R . M . DENTON, R . W . BROWNSEY, T . J . HOPKIRK & 768 G . J . BELSHAM J . BENNETT 771

J . F . A L L E N 774

W . P. WILLIAMS 776

779

881

B . P. MORGAN, A . K . C A M P B E L L , J . P. Luzio & 779 M . B . H A L L E T V . MALHOTRA & R . B . SIM 781

D . S. W . BOAM, D . R . STANWORTH, S. G . SPANNER 782 & G . B . A N S E L L

R . A . C L E G G & D . W . W E S T 783

L. C . MAHADEVAN & L. L I M 784

COMMUNICATIONS

Vol. 12

xviii CONTENTS

Regulation of multiple forms of L-serine dehydratase in mammalian liver

The effect of experimental diabetes on the level of fructose 2,6-bisphosphate in different tissues of the rat: relation­ship to glycolytic flux

D-3-Hydroxybutyrate dehydrogenase and metabolism of ketone bodies by rat stomach

Phosphoenolpyruvate carboxylase activity in the kidney of pregnant rats during late gestation

Effects of exogenous and endogenous gastric inhibitory polypeptide in obese hyperglycaemic (ob/ob) mice

Short-term effects of wheat bran supplementation on glucose and lipid metabolism in man

Studies of chick kidney alkaline phosphatase Increased phosphate incorporation into phospholipids

accompanying the substrate-mediated stimulation of phosphate uptake in chick-kidney proximal-tubule cells

Effects of cadmium on hepatic gluconeogenesis in vivo and in vitro

Use of liver snips for studies on gluconeogenesis Regulation of cyclic AMP production in rat Leydig cells by

L H RH agonist under basal and LH-stimulated conditions

Ribosomal protein S3, and not ribosomal protein S3a, is phosphorylated in Krebs I I ascites cells incubated under certain conditions

The role of Phosphagens in the survival of hypoxic stress by polychaete annelids

Anaerobiosis in Terebella lapidaria L. Immunochemical analysis of membrane-bound antigens

from Escherichia coli which have succinate dehydrogen­ase activity

Identification of a putative 5-hydroxytryptamine receptor in insect nervous tissue

Benzodiazepines modulate the A2 adenosine receptor on 108CC15 neuroblastoma x glioma hybrid cells

Rat brain membranes have specific high-affinity binding sites for N A D

Comparison between induction of glutamine synthetase by removal of glutamine and by addition of glucocorticoids in normal astrocytes and in astroglioma cells

Measurement of free calcium in synaptosomes and the effects of depolarization by potassium and glutamate

Interaction of nicotinic acetylcholine receptor from locust (Schistocerca gregarid) central nervous system with concanavalin A : comparison with vertebrate receptor

Susceptibility of muscarinic acetylcholine receptor from locust (Schistocerca gregaria) central nervous system to perturbation by ethanol and by sulphydryl reagents

Muscarinic receptor inactivation by butane-2,3-dione

Inhibition of muscarinic binding by pyridoxaI-5'-phosphate

Pyridoxal-5'-phosphate content of synaptic membrane

Radiolabelling of a-bungarotoxin to high specific radio­activity with complete retention of biological activity

Antigenic sites of the nicotinic acetylcholine receptor characterized by stability to acid denaturation

Iodination of the nicotinic acetylcholine receptor from Torpedo marmorata to high specific radioactivity with complete retention of antigenicity

M . S. EDWARDS, M . D. HITCHEN & K . S N E L L 786

M . SOCHOR, A . - M . GONZALEZ & P. M C L E A N 786

A . K . M A C G I L L , N . G . ANDERSON, 788 C . N . A . TROTMAN, J . M . CARRINGTON & P. J . HANSON C . V A L C A R C E , J . M . CUEZVA & J . M . MEDINA 789

P. R . F L A T T , C . J . BAILEY, P. KWASOWSKI, T . PAGE 790 & V . MARKS D. J . MOORE, F . J . WHITE, P. R . FLATT & 791 D. V . P A R K E M . JAHAN & P. J . BUTTERWORTH 792 R . PARVEEN, M . F . GRAHN & P . J . BUTTERWORTH 793

I . N . ROBINSON & K . SNELL 794

K . PHILIPSON & K . SNELL 795 M . H . F . SULLIVAN & B . A . COOKE 796

M . J . M C G A R V E Y & D. P. LEADER 797

B . BESTWICK & L . WARREN 799

I . ROBBINS & L . WARREN 799 R . W . JONES, J . H . WEINER & R . B . GENNIS 800

C . S. OSBORNE, R . H . OSBORNE & K . J . C A T T E L L 801

C . R . S N E L L & P. H . SNELL 802

P. H . S N E L L , C . R . SNELL & C . D. RICHARDS *04

M . D. W E I R , A . HUNT, A . J . PATEL & i05 D. G . T . THOMAS

R . D. BURGOYNE, R . CUMMING & M . J . GEISOW *06

T . ROBINSON, O . AGUILAR & G . G . L U N T 107

O . AGUILAR, M . FONSECA & G . G . L U N T 509

D. M I L L A N , J . V . SANCHEZ-ANDRES, C . R I P O L L & 510 B . SORIA

J . V . SANCHEZ-ANDRES , I . PALAFOX, C . R I P O L L , $11 D. M I L L A N & B . SORIA

C . R I P O L L , D . MILLAN, J . V . SANCHEZ-ANDRES & J12 B . SORIA

T . BARKAS & B . W . FULPIUS »13

T . BARKAS, R . W . JAMES, L . E D E R & B . W . FULPIUS \14

M . I . V E L A Z C O , T . BARKAS & B . FULPIUS 515

1>84

CONTENTS

y-Glutamyl transpeptidase from kidney and brain: a rapid purification method yields useful immunogens

Immunological distribution of cysteine sulphinate decar­boxylase (EC 4.1.1.29) in rat tissues

[3H]Galactose incorporation into bovine rods and cones

Analytical subcellular fractionation of insect central-nervous-system tissue

Isolation of postsynaptic densities from chick brain: morphology and protein/glycoprotein composition

An output of adenine derivatives from neocortical tissues modified by L-homocysteine thiolactone

Enhancement of neuromuscular transmission and contrac­tion by angiotensin I I at a skeletal muscle (rat diaphragm)

Contractures produced by angiotensin I I and acetylcholine at the rat ileum (autonomic nerve-muscle preparation)

Non-stoichiometry of ovomucoid inhibition of sperm-bound acrosin

Correlation of myosin heavy chains with ATPase staining of skeletal- and cardiac-muscle fibres

Purification and partial characterization of arginine amino-peptidases from human skeletal muscle

On the mechanism of action of the protein phosphatase de-inhibitor

Virus and pathogenesis-related protein accumulation after tobacco-mosaic-virus infection of tobacco

Binding and degradation of insulin by renal-cortical tubules

The identification of enterokinase activity in endocytotic vesicles after its clearance by hepatocytes

Preliminary studies on the characterization of a modulatory protein in the rat tapeworm Hymenolepis diminuta

Comparison between the enzymic and the immunological demonstration of prostatic acid phosphatase immobilized on agarose beads

Prostaglandins, leucocytic endogenous mediator and the acute-phase protein response to trauma

Improved sample preparation and rapid extraction of prostacyclin and thromboxane metabolites from biologi­cal samples by using reversed-phase octadecylsilyl-silica cartridges

The arachidonic acid cascade in rat liver

Arachidonic acid metabolism by rat uterus

A9- and z16-long-chain-fatty-acid desaturase activity and fatty acid composition of the chick embryo during development

Inhibition of platelet 12-lipoxygenase by hydroxy-fatty acids

Intermediates in the formation of 5,16-androstadien-3/?-ol from pregnenolone in neonatal porcine testis microsomes

Kinetic studies of 3a- and 3/?-hydroxysteroid dehydrogen­ases in neonatal porcine testis subcellular fractions

High-density-lipoprotein (HDL) subfractions in interstitial fluid from human aortic intima and atherosclerotic lesions

The effect of peroxidized lipids on thromboplastin activity Histidine-rich glycoprotein alleviates the inhibition by

heparin of thrombin-induced platelet aggregation Possible plasmid involvement in the virulence of Salmonella

dublin Rapid screening of iodinated peptides for

radioimmunoassay H + / 0 stoichiometry in plant mitochondria

xix

S. MURPHY, C . MORROW & V . L I S Y 816

P . - F . URBAN & P. REICHERT 817

W . A . K E E G A N , N . M . M C K E C H N I E & 818 C . A . CONVERSE A . K . D W I V E D Y & D . B . SATTELLE 819

K . MURAKAMI, P. R . GORDON-WEEKS & 820 S. P . R . ROSE

H . M C I L W A I N & J . D . P O L L 822

F . A . W A L I 823

F . A . W A L I 823

F . S. STEVEN & M . M . G R I F F I N 824

W . T . PERRIE & S. J . BUMFORD 825

D . MANTLE, B . LAUFFART & R . J . T . PENNINGTON 826

E. WAELKENS, J . GORIS & W . M E R L E V E D E 827

J . F . ANTONIW, R . F . WHITE, D . J . BARBARA & 828 A . L O N G L E Y J . H . THOMAS, P. G . D A V E Y , N . V . C L A R K & 829 J . JAMES

D . GRANT, S. SIDDIQUI & J . GRAHAM 829

J . B . HIPKISS & C J . BRANFORD WHITE 831

T . C . RICHARDSON & E. HEYDERMAN 832

J . W . K E Y S E R , G . L . WATKINS & C . G . CURTIS 833

I . DAS 834

S. HEWERTSON, R . G . MCDONALD-GIBSON & 835 T . F . SLATER A . MORGAN, R . G . MCDONALD-GIBSON & 837 T . F . SLATER J . H . SHAND & R . C . NOBLE 838

P. D . MITCHELL, C . HALLAM, P. E. HEMSLEY, 839 G . H . LORD & D . WILKINSON

T . K . K W A N , N . F . TAYLOR & D . B . G O W E R 841

T . K . K W A N & D . B . G O W E R 842

E. B . SMITH, C . ASHALL & J . E. W A L K E R 843

G . P . CROPPER & R . M . H O W E L L 845

G . KINDNESS , E. A . VIGROW, W . F . LONG, 846 F . B . WILLIAMSON, W . T . MORGAN & J . CHANG

E. J . MANNING, G . D . BAIRD & P. W . JONES 847

P. R . F L A T T 848

J . A . M I T C H E L L & A . L . MOORE 849

Vol. 12

XX CONTENTS

Intracellular-volume measurements of wheat-leaf meso-phyll cells and protoplasts

Membrane potential measurements in wheat-leaf meso-phyll protoplasts

Glycine decarboxylation by renal cortical mitochondria in relation to renal serine synthesis

Excretion of /?-aminoisobutyric acid in relation to lead load in humans

Effects of copper overload on hepatic intracellular organ­elles in Bedlington terriers

Erythrocyte cation transport in essential hypertension

Mechanism of uptake and intracellular translocation of [35S]cystine in cystinotic fibroblasts

The plasma amino acid flux across the placenta Electron spin resonance studies of iron uptake by intestinal

brush-border membrane vesicles The effect of wheat-bran fibre on the anaerobic metabolism

of cholic acid by mixed faecal bacteria The faecal ration of lithocholic acid to deoxycholic acid may

be an important aetiological factor in colo-rectal cancer A comparison of the effects of chenodeoxycholic acid and

ursodeoxycholic acid treatment on faecal bile acid profiles in healthy subjects

Potential Z-DNA between exons of human secreted and membrane immunoglobulin heavy-chain /i-gene

Regulation of the biosynthesis of cephamycin C by Streptomyces lactamdurans

Cloning and expression of two pab genes coding for p-aminobenzoic acid synthase, an enzyme involved in candicidin biosynthesis

Carbon catabolite regulation of penicillin biosynthesis at the oc-aminoadipic acid and oc-aminoadipyl-cyteinyl-valine levels

Proteinase activity in human brain ontogeny

Substrate metabolism in developing human brain

Fluorescence measurements of intrasynaptosomal free calcium by using a Quin dye

The incorporation of glucose into lipids of Oligodendroglia isolated from developing rat brain

Incorporation of [14C]glucose into lipids of isolated bovine Oligodendroglia: effects of normal and multiple-sclerosis sera

Placental transfer and metabolic dynamics of thyroid hormones in foetus and maternal tissues in rats

A comparison of glycosaminoglycans content of human synovial fluid in different disease states

The enhanced mucolytic activity of human pepsin 1 compared with pepsin 3: implications in peptic ulceration

Smooth muscle cell elastase: effect of in vitro ageing and lipoproteins

Bifunctional inhibitors as potential agents against elastolysis

Interaction of rat monoclonal antibodies with human killer cells ( K cells)

A highly expanded spheroidal conformation for a mucin from a cystic fibrosis patient: new evidence from electron microscopy

Electrogenic reactions of the chloroplast cytochrome b/f complex

K . L . M . V A L L E S , M . O . PROUDLOVE, 850 F . A . WILLIAMSON, R . B . B E E C H E Y & A . L . MOORE K . L . M . V A L L E S , M . O . PROUDLOVE, R . B . B E E C H E Y 851 & A . L . MOORE M . L O W R Y , M . H A L L , B . H A L L , D . H A L L & 852 J . BROSNAN D . F . E V E R E D , E . C . CRUTCHER, D . BARLTROP & 853 C D . STREHLOW

C . A . SEYMOUR & G . M . SMALL 854

B . L . WALSH, J . B . F E R R I S , J . O ' H A R E & 856 J . J . A . H E F F R O N

C . J . DANPURE, P . R . JENNINGS, S. HALSALL & 857 T . J . PETERS N . MCINTOSH, C . H . R O D E C K & R . HEATH 857 R . J . SIMPSON, M . P . W E I R , J . F . GIBSON & 859 T . J . PETERS

K . FADDEN, R . W . O W E N , M . J . H I L L & 860 A . N . MASON

R . W . O W E N , M . DODO, M . H . THOMPSON & 861 M . J . H I L L

M . DODO, R . W . O W E N , M . H . THOMPSON & 862 M . J . H I L L

C . P . MILSTEIN, E . V . DEVERSON & T . H . RABBITTS 863

J . CORTES, P. LIRAS, J . M . CASTRO, J . ROMERO & 863 J . F . MARTIN

J . A . G I L , A . REBOLLO, T . A L E G R E , P . LIRAS & 865 J . F . MARTIN

J . F . MARTIN, G . R E V I L L A , M . J . L O P E Z - N I E T O , 866 F . R . RAMOS & J . M . CANTORAL

R . G . MAHAJAN, S. MANDAL, S. K . MUKHERJEE, 867 R . BANERJEE, M . DOHADWALA, K . L . M U K H E R J E E & A . K . SINHA

A . K . SINHA, S. MANDAL, R . G . MAHAJAN, 868 S. MUKHOPADHYAYA, R . BANERJEE, M . DOHADWALA & K . L . M U K H E R J E E R . H . A S H L E Y , M . J . BRAMMER & 869 R . M . MARCHBANKS U . A Y L I F F E , N . M E L I H Y , S. M U L H A L L , C . HUGHES, 871 K . W E A V E R , A . GIBSON & M . J . BRAMMER A . GIBSON & M . J . BRAMMER 872

R . J . WOODS, A . K . SINHA & R . P . E K I N S 872

S. C . M A L I K , J . P. PEARSON & C . W . D I C K 874

J . P. PEARSON, N . B . ROBERTS & W . H . T A Y L O R 875

M . C . BOURDILLON, W . HORNEBECK, 876 J . M . SOLEILHAC & L . ROBERT

L . ROBERT, W . HORNEBECK & E . MOCZAR 876

G . H A L E , M . C L A R K & H . WALDMANN 877

P. H A L L E T T , A . J . R O W E & S. E . HARDING 878

R . W . JONES, M . A . S E L A K & J . WHITMARSH 879

1984

CONTENTS xxi

C o n t e n t s Volume 12, Part 6

SIXTH BDH L E C T U R E Quantitative cytochemistry: a precise form of cellular

biochemistry

608th M E E T I N G , K E E L E

Colloquium: The Lysosome and its Membrane Proteolytic and other metabolic pathways in lysosomes Metabolic consequences of genetic defects in lysosomes

Penetration of small molecules across the lysosome mem­brane : the 'classical' view

The lysosomal proton pump Lysosomal transport of cystine and other small molecules

Modes of access of macromolecules to the lysosomal interior Drug targeting to lysosomes

Colloquium: Post-Translational Modifications of Proteins: Mechanisms and Functions

Analysis of microsomal polypeptides involved in the co-translational translocation of secretory proteins

Processing of precursors of mitochondrial proteins The vitamin K-dependent carboxylation of proteins

Processed and non-processed forms of procollagens Influence of dopaminergic agents on ^-endorphin process­

ing in rat pars intermedia Protein disulphide-isomerase and the formation of native

disulphide bonds Post-translational modification of exogenous proteins in

Xenopus laevis oocytes

Colloquium: Biochemical Approaches to the Control of Hypertension

Localized Determinants of Vascular Smooth-Muscle Contractility

Regulation of Ca 2 + levels in smooth-muscle cells The identification of cytoplasmic membrane calcium-entry

channels by ligand-binding studies The role of the Na +,K +-ATPase in the regulation of vascu­

lar smooth-muscle contractility, and its relationship to essential hypertension

Mechanisms of the regulation of myofibrillar function in vascular smooth muscle

The Renin-Angiotensin Converting Enzyme Cascade Renin and blood pressure

Biochemistry of renin

Computer graphics modelling and specificity of renins Renin inhibitors containing 2-substituted statine

J . C H A Y E N 887

A . J . BARRETT 899 J . M . T A G E R , L . V. M . JONSSON, 902 J . M . F . G . AERTS, R . P. J . O U D E E L F E R I N K , A . W . SCHRAM, A . H . ERICKSON & J . A . BARRANGER J . B . L L O Y D 906

P. HARIKUMAR & J . P. R E E V E S 906 J . A . SCHNEIDER, A . J . JONAS, M . L . SMITH & 908 A . A . G R E E N E R . T . D E A N 911 R . DUNCAN, J . K O P E C E K & J . B . L L O Y D 913

M . A . KADERBHAI, D . H . R I D D , A . ROBINSON & 917 B . M . AUSTEN B . SCHMIDT & W . NEUPERT 920 C . VERMEER, B . A . M . SOUTE, M . U L R I C H , 922 K . HAMULYAK & M . A . G . D E BOER-VAN D E N B E R G R . TIMPL 924 J . HAM, K . G . MCFARTHING, C . I . A . TOOGOOD 927 & D . G . SMYTH R . B . FREEDMAN, B . E. BROCKWAY & 929 N . LAMBERT A . COLMAN, S. BHAMRA & G . V A L L E 932

C . CAUVIN & C . VAN BREEMEN 939 H . GLOSSMANN, A . G Ö L L , D . R . F E R R Y & 941 M . ROMBUSCH

J . K. ARONSON 943

S. B . MARSTON, C . MOODY & C . SMITH 945

M . T R E E , J . J . BROWN, B . J . L E C K I E , 948 A . F . L E V E R , P . MANHEM, J . J . MORTON, J . I . S. ROBERTSON, M . S Z E L K E & D . W E B B T . INAGAMI, K . S. MISONO, J . - J . CHANG & 951 Y . T A K I I B . L . SIBANDA 953 D . F . V E B E R , M . G . BOCK, S. F . BRADY, 956 E . H . U L M , D . W . COCHRAN, G . M . SMITH, B . I . LAMONT, R . M . DIPARDO, M . POE, R . M . FREIDINGER, B . E . EVANS & J . BOGER

Vol. 12

xxii CONTENTS

Colloquium: Exocytosis and Endocytosis Exocytosis involves highly localized membrane fusions The role of contractile filaments in secretion A possible role for endogenous protease in secretory events Contrasting roles for receptor-stimulated inositol lipid

metabolism in secretory cells The relationship between intracellular second messengers

and platelet secretion The calelectrins: new and ubiquitous Ca2+-regulated pro­

teins with a possible role in cytotic processes Processing of secretory proteins Substrate selection and processing in endocytosis

Characterization of clathrin and clathrin-associated proteins

Semliki forest virus entry and the endocytic pathway Involvement of the cortical actin filament network of

neutrophil leucocytes during phagocytosis

Colloquium: Microcomputers in Biochemistry The work of the microcomputer A low-cost Chromatograph data-collection system Microcomputers to control the pH of growing micro­

organisms The role of the microcomputer in the computing facilities of

a large research establishment Towards an automated two-dimensional gel analysis system Computer methods to aid the determination and analysis of

D N A sequences Computer graphics in the study of drug-nucleic acid

interactions The EMBL nucleotide sequence data library ZSEQ: an interactive D N A sequence analysis program

designed for microcomputers ZPEP: an interactive protein sequence analysis program

designed for microcomputers D N A sequence analysis and the computer COMMUNICATIONS LONDON M E E T I N G

Colloquium: Biochemistry of Mixed Microbial Cultures Mixed microbial culture technology Redox interactions in mixed cultures Competition between plasmid-positive and plasmid-nega-

tive cells Biochemistry of cellulose breakdown by mixed cultures Biochemistry of methanogenesis by mixed cultures Xenobiotic breakdown by mixed cultures Mixed cultures in the manufacture of cheese Fermented milks: new developments in the biochemistry of

the starter cultures

D . E. CHANDLER 961

J . P . BENNETT 963 D . A L L A N 965 S. COCKCROFT 966

D . E. K N I G H T & M . C . SCRUTTON 969

T . C SÜDHOF 972

J . A . TAYLOR, R . C . FOREMAN & J . D . JUDAH 974 J . B . L L O Y D , M . K . PRATTEN, R . DUNCAN, 977 T . KOOISTRA & S. A . C A R T L I D G E E. U N G E W I C K E L L 978

M . MARSH, M . C . K I E L I A N & A . H E L E N I U S 981 P. SHETERLINE, J . E. RICKARD & R . C . RICHARDS 983

A . THOMSON 989 J . S. L I T T L E R & C . J . P. SCOTT 991 J . A . BANGHAM & M . SYMMONS 993

M . M . JORDAN, J . E. L E W I N & J . SATCHELL 997

N . V . M C F E R R A N & T . P. Q U I G L E Y 1000 R . STADEN 1005

S. N E I D L E 1008

G. G. K N E A L E & O. KENNARD 1011 M . J . BISHOP 1015

M . J . BISHOP 1017

M . D . JONES 1018

1021

A . T . B U L L 1137 J . W . T . WIMPENNY 1138 C . A . CAULCOTT 1140

D . A . V E A L & J . M . L Y N C H 1142 D . B . ARCHER 1144 R . B . C A I N 1146 B . A . L A W 1148 V . M . E. MARSHALL 1150

BOOK R E V I E W S 1153

INDEXES Author Index 1159 Keyword Index

COMMUNICATIONS

Enzymes of the lysosomal membrane M . DOBROTA & R. H . HINTON 1021 Increased latency of acid hydrolases in the kidney cortex of PL J . HAGA, K . J . ANDERSEN , M . DOBROTA & 1022

proteinuric rats B. M . IVERSEN

1984

CONTENTS xxiii

The effect of food restriction on the latency of acid ß -glycerophosphatase in the kidney cortex of nephritic rats

Incorporation of 'acid' ß-glucosidase into phosphatidylcho­line membranes

Uptake of 1 2 5I-labelled percoll by rat visceral yolk sac cultured in vitro

Degradation of microinjected cytosolic proteins in 3T3-L1 pre-adipocytes

Immunological properties of urinary sphingomyelinase

Differential effects of leupeptin on the maturation of lysosomal a-glucosidase

Gentamicin stabilization of the rat kidney lysolemma Effects of gentamicin and cefuroxime on the rat kidney

lysolemma Latent 5'-nucleotidase in rat liver lysosomes The molecular form of gold in the human synovial

membrane after administration of gold thiomalate Changes in the colloid and lysosomes of the thyroid of rats

treated with Clofibrate Studies on the mechanism of action of a drug-carrier-

antibody conjugate Direct transfer of lymphocyte a-D-mannosidase to enzyme-

deficient human fibroblasts Mechanism of chloroquine-induced inhibition and stimula­

tion of the labelling of the intralysosomal cystine pool in cystinotic fibroblasts

The effect of chymostatin on protein degradation in 3T3 cells

Expression of sphingomyelinase in normal and Niemann-Pick disease tissues

Protein disulphide-isomerase activity of preparations used in the study of protein synthesis in vitro

Chemical modification of essential residues in purified rat liver protein disulphide-isomerase

Protein disulphide-isomerase of mature and developing wheat

Protein primary sequence studies of plasmin-derived peptides from rabbit haemopexin

Phosphorylation of the myelin-specific enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase

Inactivation of hepatic microsomal glucose-6-phosphatase by diethylpyrocarbonate

Polyamine stimulation of casein phosphorylation: differen­tial effects on the three major rat caseins

Meprin deficiency: a fault in post-translational processing? Protein synthesis by isolated rat hepatocytes: effects of

diamide and hydroperoxides Pyridoxal phosphate as a turnover label for glycogen

Phosphorylase The early stages in the biosynthesis of prothrombin Isolation of a type V I collagen precursor from bovine elastic

tissues Studies on the basement membrane of bovine retinal

microvessels Synthesis of basement membrane precursor collagen and its

incorporation into the extracellular matrix by isolated rat renal glomeruli

Identification and partial characterization of small-procol-lagen-like cartilage collagens

H . J . HAGA, K . J . ANDERSEN, M . DOBROTA, 1023 B . M . WERSEN & J . OFSTAD

M . C A R R O L L 1024

M . K . PRATTEN, L . SCARLETT & J . B . L L O Y D 1025

F . J . DOHERTY & R . J . M A Y E R 1026

A . W . SCHRÄM, G . W E I T Z , M . DRIESSEN, 1027 E . M . B R O U W E R - K E L D E R , K . SANDHOFF, J . A . BARRANGER & J . M . T A G E R R . P . J . O U D E E L F E R I N K , T . HENDRIKS, 1028 A . STRIJLAND, E . M . B R O U W E R - K E L D E R , O . DAMSMA, J . H I L K E N S , J . H I L G E R S & J . M . T A G E R S. F . B R A D L E Y , S. NOORAZAR & D . T . PLUMMER 1030

S. F . B R A D L E Y , S. NOORAZAR & D . T . PLUMMER 1031

G . A . MAGUIRE 1032

M . TAYLOR, A . T A Y L O R & R . H . HINTON 1033

S. C . PRICE, D . CHESCOE & R . H . HINTON 1034

M . C . GARNETT, E . JACOBS, M . J . EMBLETON & 1035 R . W . BALDWIN

D . ABRAHAM, B . WINCHESTER & I . O L S E N 1036

C . J . DANPURE, P . R . JENNINGS, D . A . F Y F E , 1037 S. HALSALL & T . J . PETERS

A . ANASTASI & R . T . D E A N 1039

S. J . FREEMAN, D . J . DAVIDSON, P . SHANKARAN & 1040 J . W . CALLAHAN B . E . BROCKWAY & R . B . FREEDMAN 1041

N . LAMBERT & R . B . FREEDMAN 1042

G . M . V. D E A Z E V E D O , B . E . BROCKWAY, 1043 R . B . FREEDMAN, P . G R E E N W E L L & L . T . R O D E N

C . F . A . B R Y C E , M . G . C O R D , G . KINDNESS, 1043 A . SMITH & W . T . MORGAN

J . M . BRADBURY & R . J . THOMPSON 1044

W . J . ARION, B . B U R C H E L L & A . B U R C H E L L 1045

D . W . WEST & R . A . C L E G G 1046

R . J . BEYNON, G . C . M A C A D A M & J . S. BOND 1047

A . J . WHATMORE & A . J . DICKSON 1048

P. E . B U T L E R & R . J . BEYNON 1050

M . R . EVANS, M . W . P . S U N G & M . P. ESNOUF 1051

S. A Y A D , C . A . SHUTTLEWORTH & M . E . G R A N T 1052

A . E . CANFIELD & M . E . G R A N T 1053

R . P . BOOT-HANDFORD & M . E . G R A N T 1054

C . M . K I E L T Y , D . J . S. HULMES, S. L . SCHOR & 1055 M . E . G R A N T

Vol. 12

xxiv C O N T E N T S

A new carboxypeptidase responsible for the modification in vitro of MM-creatine kinase in human plasma

The role of peptidyl dipeptidase (angiotensin converting enzyme) in the hydrolysis in vitro of gliadin by human intestinal brush-borders

Renin and kallikrein concentrations in renal tissue from spontaneously hypertensive rats during acute reduction of perfusion pressure

Determination of Captopril by an improved high-perform­ance liquid chromatography-electrochemical assay

The stability of structures containing endocytosed horse­radish peroxidase in the presence of glycyl-phenylalan-ine-2-naphthylamide

Endocytosis of sucrose by monolayers of rat hepatocytes Exocytosis of proteases by I-cell fibroblasts Fabry's disease. Identification of carrier status by fluores­

cent lectin binding Enhancement of adsorptive pinocytosis of a polyasparta-

mide by incorporation of tyramine residues Targeting of soluble cross-linked Af-(2-hydroxypropyl)-

methacrylamide copolymers in vivo. A potential drug de­livery system

Inhibition of pancreatic enzyme secretion by intracellular EGTA

Calcium translocation in the rough endoplasmic reticulum during stimulation of pancreatic enzyme secretion

Regulation of insulin secretion by human and rat islet-cell tumours

Preliminary studies on the binding of D-galactosyl- and L -fucosyl-/?-bovine serum albumins to rat hepatocytes

The identification of enterokinase activity in the Golgi complex after its clearance by hepatocytes

Fibroblast ^-glucuronidase: receptor-mediated endocytosis of secreted enzyme by other types of cell

Hepatic endosomes contain /^-adrenergic receptors but lack adenylate cyclase activity

+H-ATPase is a functional marker for hepatic endosomal membrane vesicles

Effects of calf serum on pinocytosis and proteolysis in rat yolk sacs

The mode of penetration of leupeptin into intact cells Comparative studies on the endocytosis of proteins in

kidney-tubule cells Relationship between neurotransmitter release and cytoso-

lic free calcium in PC 12 cells Dependence of exocytosis on cytosolic Ca 2 + and protein

kinase c activation in human neutrophils Recycling of N A D H pyrophosphatase in rat hepatoma cells

The involvement of transglutaminase and polyamines in insulin release from islets of Langerhans

Site of transport of immunoglobulin A in rat salivary glands

Endocytosis of insulin in rat liver leads to non-lysosomal degradation of the hormone

The roles of endocytosis and exocytosis in oxygen-radical production by polymorphonuclear leucocytes

Modification of human erythrocytes by t-butyl hydroperox­ide alters their partition behaviour in two-polymer phase systems

The dependence of cell partition in two-polymer aqueous phase systems on the electrostatic potential between the phases

R . J . EDWARDS & D. C . WATTS 1056

G . B R U C E & J . F . WOODLEY 1057

K . J . ANDERSEN, B . M . IVERSEN, M . DOBROTA, 1058 L. JOHANSEN & J . OFSTAD

D. PERRETT, S. R . R U D G E & P . L . D R U R Y 1059

M . JADOT, S. WATTIAUX-DE CONINCK & 1060 R . WATTIAUX

J . THIRION & R . WATTIAUX 1060 H . A . K H A L F A N & D. ROBINSON 1062 D. ROBINSON & H . A . KHALFAN 1063

R . DUNCAN, H . C . C A B L E , F . R Y P A C E K , 1064 J . DROBNIK & J . B . L L O Y D S. A . C A R T L I D G E , P . REJMANOVA, R . DUNCAN, 1064 J . K O P E C E K & J . B . L L O Y D

R . L . DORMER 1065

A . E . RICHARDSON, G . R . BROWN & 1066 R . L . DORMER

P. R . F L A T T & S. K . SWANSTON-FLATT 1067

R . SHARMA, N . KADERBHAI & D. G R A N T 1068

D. GRANT, S. SIDDIQUI & J . GRAHAM 1070

M . F . DEAN, B . M . JENNE, S. DIMENT & 1071 A . MCNAMARA W . H . EVANS, N . F L I N T , N . HADJIIVANOVA, 1072 C . Dix & B . COOKE T . SAERMARK, N . F L I N T & W . H . EVANS 1073

S. FORSTER & K . E . WILLIAMS 1074

S. A . C L A R K & K . E . WILLIAMS 1075

G . S. V I N C E & R . T . D E A N 1076

T . POZZAN, F . Di V I R G I L I O , G . G A T T I , N . DOZIO 1077 & J . MELDOLESI

F . Di VIRGILIO, P . D. L E W & T . POZZAN 1078

R . J . PEASE, N . D. COOK, G . D. SMITH & 1079 T . J . PETERS

P. J . BUNGAY, J . M . POTTER & M . G R I F F I N 1080

C . SANDERSON, C . P O W E L L , J . PEPPARD, 1081 R . H . HINTON & B . M . M U L L O C K

G . D. SMITH, J . R . CHRISTENSEN & T . J . PETERS 1082

M . B . H A L L E T T & A . K . CAMPBELL 1083

P. S. GASCOINE , D. P . PASHBY, C . R I C E - E V A N S & 1084

D. FISHER

P. S. GASCOINE & D. FISHER 1085

1984

CONTENTS XXV

The effect of oral immunization on the uptake of macromolecules by adult rat intestinal columnar epithe­lium and Peyer's patch tissue in vitro

The uptake of macromolecules by adult rat intestinal columnar epithelium and Peyer's patch tissue in vitro

A cytoskeleton from synaptosomes which is rich in a spectrin-like protein

Substrate dependency of gastric acid secretion: effect of metabolic substrates on aminopyrine accumulation by rat parietal cells

Is mucin secretion from rat submandibular acini triggered by a rise in intracellular Ca 2 + concentration

Neurotensin modulation of the plasma insulin response to glucose in obese hyperglycaemic (ob/ob) mice

Metabolic maps for the Apple I I Microcomputer-controlled collection of haemoglobin-oxy­

gen binding curves Three-dimensional computer graphics on a Sinclair

Spectrum Computer graphic display of a large multisubunit protein:

Escherichia coli aspartate transcarbamoylase Microcomputer control of liquid chromatography

A microcomputer system for the detection, integration and area apportionment of g.l.c. elution profiles

A graphics-based teaching program A microcomputer implementation of the D I A G O N

sequence comparison and alignment program Nucleic acid sequencing package for the BBC micro­

computer Quantification of cholesteryl sulphate in human faeces Diet and steroid composition in ileostomy fluid

Site of cholesterol degradation in the human gut Steroid degradation along the gastrointestinal tract: the use

of the cannulated pig as a model system The characterization of calpains and calpain inhibitors

from chicken gizzard smooth muscle The human glutathione S-transferases: developmental

aspects of the GST1 and GST3 loci The metabolism of lithocholic acid-3ot-sulphate by Pseudo­

monas sp. NC 18 10590 under anaerobic conditions Glutathione and glutathione S-transferase levels in mouse

bone marrow after cyclophosphamide administration Purification and properties of human liver cathepsin L Comparison of human low-molecular-weight RNA from

normal and Crohn's disease derived blood and mesenteric lymph node leucocytes

Metabolism of testosterone by human gingival fibroblasts in culture

Steroid metabolism by human axillary bacteria

A study of bile salt binding by human liver cytosol

The breakdown of gliadin peptides by rat intestinal brush-borders in vitro

Characterization of the human thyroid microsomal antigen involved in the thyroid autoimmunity

Activation of carbonic anhydrase I I I by active-site modification

An enzyme-linked immuno-adsorbent assay for the quanti­fication of neurofilament protein levels in cell cultures initiated from human foetal nervous tissue

S. J . BEAHON & J . F . WOODLEY 1087

S. J . BEAHON & J . F . WOODLEY 1088

J . E . H E S K E T H 1089

N . G . ANDERSON, G . P. SHAW & P. J . HANSON 1090

M . A . MCPHERSON & R . L . DORMER 1091

C . J . B A I L E Y & P. R . F L A T T 1092

M . R . WATSON 1093 R . A . PENNY & D . A . F E L L 1094

M . J . C . CRABBE 1095

E . J . M I L N E R - W H I T E & S. M C L E O D 1097

C . D . MCFARLAND, S. PRICE, R . A . BROWN & 1098 M . J . H A R V E Y I . G . G I L E S 1099

N . V. M C F E R R A N 1100 I . G . G I L E S 1101

R . W . WESTLAKE & D . S. R O E 1102

R . W . O W E N & M . H . THOMPSON 1102 F . FERNANDEZ, H . KENNEDY, E . TODD, 1103 S. T R U E L O V E & M . H I L L J . A . BOYER, D . W . D A Y & M . J . H I L L 1104 K . FADDEN, R . W . OWEN, M . J . H I L L , 1105 E . LATYMER, A . G . LOW & A , N . MASON P. JOHNSON, C . PARKES & A . J . BARRETT 1106

B . A . DAVIS, C . G . FAULDER, W . COTTON, 1108 A . D . BAIN, R . HUME & R . C . STRANGE R . W . O W E N & R . F . BILTON 1109

D . J . ADAMS, J . CARMICHAEL, J . F . SMYTH & 1110 C . R . W O L F R . W . MASON & A . J . BARRETT 1111 P. D . BUTCHER, C . M . STRANGE, J . M C F A D D E N & 1112 J . HERMON-TAYLOR

M . SOORIYAMOORTHY, W . H A R V E Y & 1113 D . B . G O W E R

A . NIXON, P. J . H . JACKMAN, A . I . M A L L E T & 1114 D . B . G O W E R

A . J . SCRIVEN , I . A . NIMMO, R . HUME & 1115 R . C . STRANGE

G . B R U C E & J . F . WOODLEY 1116

J . P . BANGA, G . P R Y C E , L . HAMMOND & 1118 I . M . ROITT

W . R . CHEGWIDDEN, D . HEWETT-EMMETT & 1119 R . E . TASHIAN

P. DOHERTY, J . G . DICKSON & F . S. WALSH 1120

Vol. 12

xxvi CONTENTS

Development of choline acetyltransferase activity in motor neuron-enriched primary cultures of chick embryo spinal cord

Subcellular localization of esterase, lipase and sulphatase activities in human neutrophils

Ca 2 +-mobilizing hormones increase Ca 2 + influx in isolated rat hepatocytes

Cytosolic Ca 2 + variations induced by specific receptor-mediated stimulation in male and female rat hepatocytes

Inhibition of phospholipase A 2 by serum albumin

Inosine-induced vasoconstriction and glucose secretion in the perfused rat liver

Maternofetal transmission of immunoglobulin G : an ap­proach in vitro

Influence of proliferation of cultivated endothelial and smooth-muscle cells on activities and expression of glycosyltransferase

Analysis of keto compounds in blood by high-performance liquid chromatography

Azurin from Pseudomonas putida: an electron acceptor for /7-cresol methylhydroxylase

Effect of toxaphene on photosynthetic electron flow in susceptible cereals

Amino acid sequence of Rhodymenia palmata ferredoxin

Minor faecal bile acids and large-bowel cancer

T . P. FLANIGAN, J . G . DICKSON & F . S. WALSH 1122

N . J . H A C K , G . P . SMITH & T . J . PETERS 1123

J . - P . MAUGER, J . POGGIOLI, F . GUESDON & 1123 M . C L A R E T A . BINET, B . BERTHON & M . C L A R E T 1124

S. FORSTER , E. ILDERTON, R . SUMMERLY & 1125 H . J . Y A R D L E Y

R . J . SHARMA & J . R . G R I F F I T H S 1126

L . C . W . SEYMOUR & K . E. WILLIAMS 1128

P. VlSCHER & E. B U D D E C K E 1129

T . G . VICKERS & R . A . O W E N 1130

M . J . CAUSER, D . J . HOPPER, W . S. MCINTIRE & 1131 T . P . SINGER S. AKBAR & L . J . ROGERS 1132

K . INOUE, T . HASE, H . MATSUBARA, 1133 M . P . F I T Z G E R A L D & L . J . ROGERS R . W A I T & M . H . THOMPSON 1134

1984

606th MEETING, CORK 373

Transport of Proteins, Ions and Electrons Through Mitochondrial Membranes

Biochemical Society/International Union of Biochemistry Joint Symposium organized and edited by S . Doonan and J . J . A. Heffron (Cork) and L. Packer (University

of California)

Import of mitochondrial proteins MATTHEW A. HARMEY* and WALTER NEUPERTf * Department of Botany, University College, Dublin, Ireland, and f Institut für Biochemie, Georg-August Universität, Göttingen, West Germany

Most mitochondrial proteins are encoded in the nuclear genome and are translated on the cytoplasmic ribosomes in the form of precursors (Neupert & Schatz, 1981). These pre­cursors are synthesized mainly on free ribosomes and run off to form a cytosolic pool, from which they are transferred into the mitochondria (Zimmermann et al., 1979; Freitag et al.9 1982a; Schatz & Butow, 1983). The pool sizes for indivi­dual precursors are characteristically very small and are quite difficult to detect. Recent studies using uncouplers have, however, made possible the demonstration of cyto­solic pools for quite a number of mitochondrial proteins (Reid & Schatz, 1982; Schmidt et al., 1983A). In yeast cells, in particular, it has been possible to accumulate substantial quantities of precursor (Reid & Schatz, 1982).

The overall process of import may be dissected into a number of distinct but concatenated steps: (I) mitochon­drial recognition of precursors; (II) translocation of the pre­cursor across the mitochondrial membranes; ( I I I ) process­ing of precursor protein; (IV) assembly to multimeric com­plexes.

Recognition of precursor is mediated by receptors in the mitochondrial outer surface. The recognition is specific in that it discriminates between precursor and mature forms of individual proteins. When mitochondria are treated with trypsin, they no longer bind precursors, an observation which suggests that the recognition factors are surface pro­teins of the outer membrane. When Neurospora mitochon­dria were incubated in the presence of apocytochrome c and holocytochrome c, the apo form was selectively imported. The presence of a large excess of the holocytochrome did not decrease the import of the apoprotein (Korb & Neupert, 1978). The binding of the precursor can only be effectively demonstrated when the further progress of the precursor is inhibited. With apocytochrome c, addition of deutero-haemin prevents import, but does not hinder binding (Hennig & Neupert, 1981). For the ADP/ATP carrier and subunit 9 of ATPase, depletion of the membrane potential may be used to achieve arrest at the binding stage (Schleyer etat., 1982; Schmidt et al., 1983a). The bound precursor can be exchanged for precursor, but not for the mature protein (Hennig & Neupert, 1981). The precursors bind in a satur­able manner, and for apocytochrome c Scatchard plots have indicated the presence of high-affinity receptors with a fre­quency of 90pmol/mg of mitochondrial protein (Hennig et

al., 1983). I t is not known, however, whether each indivi­dual protein has a specific receptor protein. The electro-phoretic profiles of the outer membrane would not support such a view, and further, there is evidence from competition studies that a number of precursors compete for both bind­ing and import. On the other hand, the receptor for apocyto­chrome c is highly specific. A partially purified receptor has been isolated and inserted into liposomes, where it shows the same high affinity and specificity as in the intact mito­chondria (H. Koehler, B. Hennig & W. Neupert, unpub­lished work). When inhibition of import was removed from mitochondria to which precursors had been bound, the bound precursors were directly imported without intermedi­ate displacement (Zwizinski et al., 1983). I t appears that the receptors not only sort the precursors but also steer them to the next stage of the import process.

In general the transfer of precursor from the bound state, in which it is accessible to added proteinases, into the mito­chondria, where it becomes inaccessible to added pro­teinase, requires an electrical transmembrane potential (Schleyer et al., 1982). The electrical potential may be gener­ated by the addition of ATP, but it has been convincingly demonstrated that it is the membrane potential and not the ATP, in itself, which is the requirement. The exact role of the membrane potential is unclear. I t is not known whether the potential is needed to provide energy for the transport, or i f it triggers the transmembrane movement with attend­ant conformational changes in the incoming proteins. The transport of all precursors does not require a membrane potential; notable exceptions are apocytochrome c and the precursor to the outer-membrane protein porin (Freitag et al., 19826; Zimmermann et al, 1981). Neither of these pre­cursors has to insert into, or cross, the inner membrane, which is the site of the membrane potential; hence they have no need of an energy source.

The transfer of many precursors is accompanied by a proteolytic processing step (Daum etal., 1982). The process­ing is carried out by a matrix-located metalloenzyme which cleaves the precursor to the mature size. The proteinase can be inhibited by chelators without inhibiting the import process, so that one can differentiate between transport and proteolysis, although these processes are linked in vivo (C. Zwizinski & W. Neupert, unpublished work). A matrix-located enzyme which is not synthesized as a higher-molecular-weight precursor has recently been described, an observation which reinforces the separateness of trans­port and proteolytic processing (Hampsey et al., 1983). This observation also is in accord with the observed behaviour of proteins such as the ADP/ATP carrier, which is not synthesized as a larger precursor, but which requires a mem-

Vol. 12

374 BIOCHEMICAL SOCIETY TRANSACTIONS

brane potential for transfer and insertion into the inner membrane.

A few precursor proteins are processed in two steps; cyto­chrome c{ is such a case (Gasser et al, 1982; Teintze et al.9

1982). The first step is by the matrix proteinase. The second, haeme-dependent, cleavage is effected by a proteinase which is apparently independent of a membrane potential, is not inhibited by chelators, and appears to be located at or near the outer face of the inner membrane. The intermedi­ate form can be seen in cells pulse labelled at 8°C. The con­version of the intermediate into mature form can also be followed in mitochondria from cells labelled at 8°C. The proteolytic processing and its requirements for a membrane potential in intact mitochondria can be attributed to the location of the proteinase in the mitochondrial matrix. Al l polypeptides requiring proteolytic cleavage must therefore traverse the inner membrane, in part at least, and thus re­quire a membrane potential to do so.

The final step in the transport process, i.e. assembly of the imported subunits into functional complexes, and the fac­tors controlling this step have not been extensively studied. There is evidence of an interaction between availability of subunits in mitochondria and those supplied by the cyto-solic system (von Rucker & Neupert, 1976; Lustig et al, 1982). On the other hand there is evidence to show the absence of a close coupling between the supply of subunits from cytosol and mitochondria in the assembly of the cyto­chrome bcl complex in Neurospora (Weiss & Kolb, 1979). In this context it has been shown that in vitro imported ADP/ATP carrier displays the characteristics of the as­sembled mature complex (M. Schleyer & W. Neupert, un­published work). Import of subunit 9 of the ATPase results in incorporation of precursor into an immunoprecipitable ATPase complex (Schmidt et al, 1983A). These latter two proteins may provide models to study the assembly process further.

The import mechanism is specific for recognition and im­port of mitochondrial precursors. When mRNA from Neurospora crassa is translated in rabbit reticulocyte lysates, the post-ribosomal supernatant contains a mixture of pro­teins. Mitochondria will selectively import mitochondrial-specific proteins from this heterogeneous protein mixture. The recognition system is, however, also capable of recog­nizing precursor proteins from unrelated species, as shown by import studies with subunit 9 of the ATPase. Neurospora subunit 9 is imported by yeast mitochondria from a reticulo­cyte lysate supernatant, programmed with Neurospora mes­sage, and furthermore is correctly processed by a matrix protease (Schmidt et al, 1983ft). In yeast this subunit

is coded in the mitochondrial D N A and is translated on mitochondrial ribosomes (Tzagoloff & Meagher, 1972). A similar situation has been described for mammalian tissues, where mitochondria from tissues which do not pro­duce ornithine transcarbamoylase can nonetheless import and correctly process the precursor (Morita et al, 1982). I t appears therefore that the recognition, translocation and proteolytic processing mechanisms are highly conserved during eukaryotic evolution.

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