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Metabolism of saccharides Vladimíra Kvasnicová

Metabolism of saccharides Vladimíra Kvasnicová. Glucose enter the cells by a)free diffusion b)facilitated diffusion c)active transport d)secondary active

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Metabolism of saccharidesVladimíra Kvasnicová

Glucose enter the cells by

a) free diffusion

b) facilitated diffusion

c) active transport

d) secondary active transport

Glucose enter the cells by

a) free diffusion

b) facilitated diffusion

c) active transport

d) secondary active transport

Insulin-dependent transport of glc into the cell is found in the

a) liver

b) erytrocyte

c) adipose tissue

d) muscle

Insulin-dependent transport of glc into the cell is found in the

a) liver

b) erytrocyte

c) adipose tissue

d) muscle

Glucose transport into cells: facilitated diffusion

(protein transporter GLUT – various types)

ERYTROCYTES NERVOUS TISSUE

- insulin-independent transport

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

HEPATOCYTES

- insulin-independent transport

FATTY TISSUE MUSCLES

- insulin-DEPENDENT transport

insulin increases number of glc transporters

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

The figure was accepted from Trends in Biochemical Sciences, reference edition, volume 6, str. 209.

Elsevier/North-Holland Biomedical Press, 1981.

The figure was accepted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2

Secondary-active transport of GLC: symport with Na+

- small intestine, kidneys

Glucose from a diet can be used

a) as an energy source for cells

b) for glycogen synthesis

c) for formation of fat (= energy store)

d) as a main substrate for production of NADPH

Glucose from a diet can be used

a) as an energy source for cells

b) for glycogen synthesis

c) for formation of fat (= energy store)

d) as a main substrate for production of NADPH

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

Glc-6-P !!!

+ NADPH

= hepatocyte

The figure was accepted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2

1st phase

2nd phase

3rd phase

The figure is found at http://web.indstate.edu/thcme/mwking/glycolysis.html (Jan 2007)

The enzymes you must know

The figure is found at http://web.indstate.edu/thcme/mwking/glycolysis.html (Jan 2007)

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

2

2

Products of aerobic glycolysis

Products of anaerobic glycolysis

NADHwas consumed in

conversion of pyruvate to

lactate

Glycolysis(= oxidative cleavage of glucose)

a) is located in a mitochondrion

b) can proceed under anaerobic conditions as well

c) produces 2 moles of pyruvate / 1 mole of Glc

d) generates 2 moles of ATP as a net energy acquisition

a) is located in a mitochondrion

b) can proceed under anaerobic conditions as well

c) produces 2 moles of pyruvate / 1 mole of Glc

d) generates 2 moles of ATP as a net energy acquisition

Glycolysis(= oxidative cleavage of glucose)

Enzyme hexokinase

a) catalyzes esterification of glucose

b) has higher affinity to glucose than glucokinase

c) phosphorylates fructose as well

d) is found in a cytoplasm of many cells

Enzyme hexokinase

a) catalyzes esterification of glucose

b) has higher affinity to glucose than glucokinase

c) phosphorylates fructose as well

d) is found in a cytoplasm of many cells

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

IRREVERSIBLE REACTION

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

Enzyme 6-phosphofructokinase-1 (PFK-1)

a) is a main regulatory enzyme of glycolysis

b) converts fructose-1,6-bisphosphate to fructose-6-phosphate

c) is activated by citrate and ATP/ADP

d) is regulated by insulin

Enzyme 6-phosphofructokinase-1 (PFK-1)

a) is a main regulatory enzyme of glycolysis

b) converts fructose-1,6-bisphosphate to fructose-6-phosphate

c) is activated by citrate and ATP/ADP

d) is regulated by insulin

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

IRREVERSIBLE REACTION

NADH+H+ forming in glycolysis

a) is a coenzyme of oxidoreductases

b) can be reoxidized back to NAD+ in a conversion of pyruvate to lactate

c) can be used in a reduction of malate to oxaloacetate

d) is a source of reducing equivalents enteringa respiratory chain, but only under aerobic conditions

NADH+H+ forming in glycolysis

a) is a coenzyme of oxidoreductases

b) can be reoxidized back to NAD+ in a conversion of pyruvate to lactate

c) can be used in a reduction of malate to oxaloacetate

d) is a source of reducing equivalents enteringa respiratory chain, but only under aerobic conditions

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

2

2

Products of aerobic glycolysis

Products of anaerobic glycolysis

NADHwas consumed in

conversion of pyruvate to

lactate

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

MALATE-ASPARTATE SHUTTLE

Transport of reducing equivalents to mitochondria

The figure was accepted

from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc.,

New York, 1997. ISBN 0‑471‑15451‑2

GLYCEROL PHOSPHATE SHUTTLE

The figure was accepted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2

2,3-bisphosphoglycerate (2,3-BPG)

a) belongs among energy rich compounds

b) is formed from glyceraldehyde-3-phosphate by phosphorylation using inorganic phosphate

c) can be transformed to 3-phosphoglycerate, ATP is simultaneously formed from ADP

d) is formed only in the liver as a shunt of glycolysis

2,3-bisphosphoglycerate (2,3-BPG)

a) belongs among energy rich compounds

b) is formed from glyceraldehyde-3-phosphate by phosphorylation using inorganic phosphate

c) can be transformed to 3-phosphoglycerate, ATP is simultaneously formed from ADP

d) is formed only in the liver as a shunt of glycolysis

2,3-BPG shunt

IN ERYTROCYTES:

2,3-BPG affinity of Hb to O2

The figure was accepted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2

ATP is formed in the reactions of glycolysis

a) phosphoenolpyruvate (PEPA) → pyruvate

b) glucose → glucose-6-phosphate

c) fructose-1,6-bisphosphate→ fructose-6-phosphate

d) glyceraldehyde-3-phosphate→ 1,3-bisphosphoglycerate

ATP is formed in the reactions of glycolysis

a) phosphoenolpyruvate (PEPA) → pyruvate

b) glucose → glucose-6-phosphate

c) fructose-1,6-bisphosphate→ fructose-6-phosphate

d) glyceraldehyde-3-phosphate→ 1,3-bisphosphoglycerate

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

= substrate level phosphorylation(ATP formation using energy released from

cleavage of an energy rich compound = macroergic compound)

IRREVERSIBLE REACTION

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

= substrate level phosphorylation

Pi +

Pyruvate can be transformed by

a) carboxylation to acetyl-CoA

b) reduction to lactate

c) oxidative decarboxylation to oxaloacetate

d) transamination to aspatate

Pyruvate can be transformed by

a) carboxylation to acetyl-CoA

b) reduction to lactate

c) oxidative decarboxylation to oxaloacetate

d) transamination to aspatate

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

= transamination

= carboxylation = oxidative decarboxylation

= reduction

Choose correct statements about regulation of glycolysis

a) it is activated by insulin

b) it is activated by glucagon

c) regulatory enzymes of glycolysis are kinases

d) pH inhibits glycolysis

Choose correct statements about regulation of glycolysis

a) it is activated by insulin

b) it is activated by glucagon

c) regulatory enzymes of glycolysis are kinases

d) pH inhibits glycolysis

regulatory enzyme activation inhibition

hexokinase glucose-6-phosphate

glucokinase insulin (induction) fructose-1-phosphate (liver)

fructose-6-phosphate

6-phosphofructo-1-kinase (PFK-1)

main regulatory enzyme

(key enzyme)

ATP / AMP fructose-2,6-bisphosphate ( if insulin / glucagon) insulin (induction)

ATP / AMP citrate acidic pH

pyruvate kinase insulin (induction) fructose-1,6-bisphosphate (feed foreward regulation)

glucagon (repression, inhibition by phosphorylation) ATP / AMP acetyl-CoA

Regulation of glycolysis

The figure was found at http://www.biochem.arizona.edu/classes/bioc462/462b/graphics/GlycolysisGN

GLehn4Fig14-16.jpg (Dec 2007)

Gluconeogenesis

proceeds as a „reversed glycolysis“

with exception of3 reactions !

The figure has been adopted from J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2nd edition, Thieme 2005

glucose entering

glycolysis

pyruvateentering

gluconeogenesis

Gluconeogenesis

= formation of glucose from

non sugar precursors

The figure was found at http://www2.mcdaniel.edu/Chemistry/CH3321JPGs/Metabolism/Gluconeogenesis.jpg (Dec 2007)

Enzymes of gluconeogenesis(= synthesis of glucose „de novo“)

a) are found in a cytoplasm only

b) are active mainly in a brain and erytrocytes

c) are completely the same as enzymes of glycolysis (catalyze oposite reactions of glycolysis)

d) are not found in the liver

a) are found in a cytoplasm only

b) are active mainly in a brain and erytrocytes

c) are completely the same as enzymes of glycolysis (they catalyze oposite reactions of glycolysis)

d) are not found in the liver

Enzymes of gluconeogenesis(= synthesis of glucose „de novo“)

Choose substrates of gluconeogenesis

a) acetyl-CoA

b) pyruvate

c) glycerol

d) lactate

Choose substrates of gluconeogenesis

a) acetyl-CoA

b) pyruvate

c) glycerol

d) lactate

Cori cycle

and muscle

The figure was accepted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2

Glucose-alanine cycle

The figure was accepted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2

= tuk

The figure was accepted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2

Choose enzymes of gluconeogenesis

a) pyruvate kinase

b) PEP carboxykinase

c) pyruvate carboxylase

d) pyruvate dehydrogenase

Choose enzymes of gluconeogenesis

a) pyruvate kinase

b) PEP carboxykinase

c) pyruvate carboxylase

d) pyruvate dehydrogenase

The figure is found at http://faculty.uca.edu/~johnc/pdhrxns.gif (Jan 2006)

Pyruvate DeHydrogenase complex is found in mitochondria

(multienzyme complex, PDH)

The reactions participate in gluconeogenesis

a) pyruvate + CO2 → oxaloacetate

b) pyruvate + ATP → phosphoenolypyruvate

c) fructose-1,6-bisphosphate → fructose-6-phosphate + ATP

d) glucose-6-phosphate → glucose + ATP

The reactions participate in gluconeogenesis

a) pyruvate + CO2 → oxaloacetate

b) pyruvate + ATP → phosphoenolypyruvate

c) fructose-1,6-bisphosphate → fructose-6-phosphate + ATP

d) glucose-6-phosphate → glucose + ATP

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

in MITOCHONDRIA only

Gluconeogenesis is

a) activated by insulin

b) inhibited by citrate

c) activated by AMP

d) inhibited by glucagon

Gluconeogenesis is

a) activated by insulin

b) inhibited by citrate

c) activated by AMP

d) inhibited by glucagon

the opposite answers are correct

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

Gluconeogenesis

regulatory enzyme activation inhibition

pyruvate carboxylase acetyl-Co A cortisol, glucagon (induction)

insulin (repression)

phosphoenolpyruvatecarboxykinase

cortisol, glucagon (induction)

insulin (repression)

fructose-1,6-bisphosphatase

cortisol, glucagon (induction)

AMP / ATP fructose-2,6-bisphosphate ( if insulin / glucagon) insulin (repression)

glucose-6-phosphatase

cortisol, glucagon (induction)

insulin (repression)

Regulation of gluconeogenesis

GLYCOGEN (Glc)n

The figure was found at http://students.ou.edu/R/Ben.A.Rodriguez-1/glycogen.gif (October 2007)

nonreducing end reducing end

OH

Metabolism of glycogen

a) is regulated by glycogen synthase and glycogen phosphorylase

b) is located in a cytoplasm

c) is regulated by insulin

d) proceeds on reducing ends of glycogen molecule

Metabolism of glycogen

a) is regulated by glycogen synthase and glycogen phosphorylase

b) is located in a cytoplasm

c) is regulated by insulin

d) proceeds on reducing ends of glycogen molecule

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

Metabolism of glycogen see http://www-fgg.eur.nl/ow/coo/bioch/

During glycogen synthesis(= glycogenesis)

a) Glc-6-P is transformed to UDP-6-glc

b) glycogen synthase participates in a formation of both (1→4) and (1→6) glycosidic bonds

c) macroergic phosphate is consumed

d) is glycogen synthase activated by glucagon

a) Glc-6-P is transformed to UDP-6-glc

b) glycogen synthase participates in a formation of both (1→4) and (1→6) glycosidic bonds

c) macroergic phosphate is consumed

d) is glycogen synthase activated by glucagon

During glycogen synthesis(= glycogenesis)

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

During degradation of glycogen within cells

(= glycogenolysis)

) (1→6) glycosidic bonds are split by glycogen phosphorylase

b) glucose is transfered to phosphate: glc-1-P is formed as a product of the degradation

c) (1→4) bonds are split hydrolytically

d) 1 ATP is consumed if 1 glc is released

During degradation of glycogen within cells

(= glycogenolysis)

) (1→6) glycosidic bonds are split by glycogen phosphorylase

b) glucose is transfered to phosphate: glc-1-P is formed as a product of the degradation

c) (1→4) bonds are split hydrolytically

d) 1 ATP is consumed if 1 glc is released

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

If glycogenolysis is followed by glycolysis

a) the net gain of the anaerobic glycolysis is3 ATP

b) the process is called gluconeogenesis

c) both the cytoplasmatic and mitochondrial enzymes participate in the reactions

d) oxaloacetate is formed as an intermediate

If glycogenolysis is followed by glycolysis

a) the net gain of the anaerobic glycolysis is3 ATP

b) the process is called gluconeogenesis

c) both the cytoplasmatic and mitochondrial enzymes participate in the reactions

d) oxaloacetate is formed as an intermediate

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)

glycogen glucose

ATP

ADPPi

regulatory enzyme activation inhibition

glykogen phosphorylase(glycogen degradation)

glucagon, adrenaline (phosphorylation)

ATP / AMP Ca2+ (muscle)

ATP / AMP glucose-6-phosphate glucose

glykogen synthase(glycogen synthesis)

insulin (induction) glucose-6-phosphate

glucagon, adrenaline (phosphorylation)

Regulation of glycogen metabolism

The figure is found at http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-3/ch15_pentose-alternatives.jpg (Dec 2006)

Pentose cycle(= Hexose MonoPhosphate Pathway, HMPP)

IRREVERSIBLE

REVERSIBLE(interconversion of saccharide monophosphat

es)

The figure is found at http://web.indstate.edu/thcme/mwking/pentose-phosphate-pathway.html (Dec 2006)

The figure is found at http://web.indstate.edu/thcme/mwking/pentose-phosphate-pathway.html (Dec 2006)

intermediates of glycolysis

synthesis of

nucleotides

Pentose cycle(= Hexose MonoPhosphate Pathway,

HMPP)

a) is located in a cytoplasm

b) includes direct oxidation of glucose monophosphate

c) is a shunt of glycolysis (products of HMPP can enter glycolysis)

d) produces pentoses

Pentose cycle(= Hexose MonoPhosphate Pathway,

HMPP)

a) is located in a cytoplasm

b) includes direct oxidation of glucose monophosphate

c) is a shunt of glycolysis (products of HMPP can enter glycolysis)

d) produces pentoses

The figure is found at http://www.richmond.edu/~jbell2/14F34.JPG (Dec 2006)

Choose enzymes of HMPP

a) transketolase

b) transaminase

c) glucose-6-phosphate dyhydrogenase(glc-6-P DH)

d) pyruvate carboxylase

Choose enzymes of HMPP

a) transketolase

b) transaminase

c) glucose-6-phosphate dyhydrogenase(glc-6-P DH) = regulatory enzyme

d) pyruvate carboxylase

Pentose cycle

a) produces NADPH which can be oxidized in a respiratory chain → energy is produced

b) generates saccharides used in a glycoprotein synthesis

c) forms ribose-5-phosphate a substrate of nucleic acids synthesis

d) forms fru-6-P and glyceraldehyde-3-P which can enter glycolysis or gluconeogenesis

Pentose cycle

a) produces NADPH which can be oxidized in a respiratory chain → energy is produced

b) generates saccharides used in a glycoprotein synthesis

c) forms ribose-5-phosphate a substrate of nucleic acids synthesis

d) forms fru-6-P and glyceraldehyde-3-P which can enter glycolysis or gluconeogenesis

If NADPH accumulates

a) oxidative part of HMPP is inhibited

b) ribose-5-phosphate can not be synhesized

c) glc-6-P dehydrogenase is activated

d) the reversible reactions of the HMPP can only proceed

If NADPH accumulates

a) oxidative part of HMPP is inhibited

b) ribose-5-phosphate can not be synhesized

c) glc-6-P dehydrogenase is activated

d) the reversible reactions of the HMPP can only proceed

The figure is found at http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-3/ch15_pentose-alternatives.jpg (Dec 2006)

Regulation of HMPP

• on the level of substrates availability and products consumption

NADPH / NADP+

reaction using NADP+ are inhibited by lack

of the coenzyme

Fructose

a) is metabolized mainly in the liver

b) can be transformed to fru-6-P by fructokinase

c) can be formed from sorbitol as well

d) can be transformed to glucose

Fructose

a) is metabolized mainly in the liver

b) can be transformed to fru-6-P by fructokinase

c) can be formed from sorbitol as well

d) can be transformed to glucose

Metabolism of fructose in the liver

The figure is found at http://web.indstate.edu/thcme/mwking/glycolysis.html (Jan 2007)

glycolysis or gluconeogenesis

The figure was accepted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley‑Liss, Inc., New York, 1997. ISBN 0‑471‑15451‑2

When Fru is converted to Fru-1-P

a) it can be split by an aldolase to glyceraldehyde and dihydroxyacetone phosphate

b) is fructose metabolised in glycolysis faster then glucose

c) glyceraldehyde made by spliting of fru-1-P can be converted to glycerol

d) glucokinase can be activated by fru-1-P

When Fru is converted to Fru-1-P

a) it can be split by an aldolase to glyceraldehyde and dihydroxyacetone phosphate

b) is fructose metabolised in glycolysis faster then glucose

c) glyceraldehyde made by spliting of fru-1-P can be converted to glycerol

d) glucokinase can be activated by fru-1-P

Glucose can be converted to

a) galactose: glc-6-P → gal-6-P

b) fructose: glc → glucitol → fru

c) glucuronic acid: UDP-glc + 2 NAD+ → UDP-glukuronate + 2 NADH+H+

d) ribose: glc-6-P → → ribulose-5-P → rib-5-P

Glucose can be converted to

a) galactose: glc-6-P → gal-6-P

b) fructose: glc → glucitol → fru

c) glucuronic acid: UDP-glc + 2 NAD+ → UDP-glukuronate + 2 NADH+H+

d) ribose: glc-6-P → → ribulose-5-P → rib-5-P

Metabolism of galactose

The figure is found at http://web.indstate.edu/thcme/mwking/glycolysis.html (Jan 2007)

epimerization

proceeds on the level of UDP-

derivatives

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)