not actually derived from acetate. The oxidation of acetate is a cyclic process in which the 'carrier ' , oxaloacetate, is regenerated; consequently all that is required is that the net products of each cycle, irrespective of their origin, are those demanded by the stoichiometry of acetate oxidation.

In view of this it seems much more logical to regard succinate production as a result of the oxidation of acetate rather than as a prerequisite for it. A comparison of the structures of oxalo- acetate and succinate shows that the reactions in the cycle which are involved in the production of carbon dioxide effectively reduce the carbonyl group in the former to a methylene group in the latter. 2 The remainder of the cycle is then concerned, not with oxidising the methyl group of acetate (it has already, in effect, been oxidised) but with regenerating oxaio-acetate. In doing so, this part of the cycle produces the remaining reducing equivalents necessary to account for the stoichiometry of acetate oxidation. In fact, however, only 50% of the reducing equiv- alents produced in this part of the cycle actually originate from what was the methyl carbon of acetate. One methylene carbon in succinate is derived from the acetate methyl group, the other is derived from oxalo-acetate. However, because succinate de- hydrogenase cannot discriminate between the two carboxyl groups of succinate 3 and because the carboxyl groups in fumarate are sterically completely equivalent, both methylene groups will be oxidised equally. This again illustrates the fact that it is the stoichiometry of the cycle which is important; the precise origin of the products is not.

R W Hanson Polytechnic South West

Faculty of Science Department of Biological Sciences

Drake Circus, Plymouth, Devon PL4 8AA, UK

References IWeitzman, P D J (1992) Biochem Educ 20, 21 2Hanson, R W (1990) Biochem Educ 18, 194-196 3Lehninger, A L (1970) 'Biochemistry', Worth, NY, p 354

T C A Cycle: Professor W e i t z m a n replies

Dear Sir, The starting point of my 'scheme' is the potential confusion for students over the need for the initial condensation of a 2-carbon compound with a 4-carbon one, to form a 6-carbon product. Textbooks of biochemistry fail to address this question and offer no rationale. I set out to provide an explanation for the apparent mystery and to offer a simplistic chemical rationale as an aid to students struggling to ' learn' the citric acid cycle.

My scheme starts with the difficulty of oxidising acetic acid, goes on to show how, by comparison, oxidation (dehydro- genation) is possible with succinic acid, and thus provides the student with a rationale for the set of reactions which appear to start with acetic acid and, part way round the cycle, go through the stage of succinic acid. The student is also prompted towards an understanding of the cyclic nature of the process. I concluded that "Recognition of these relatively simple chemical consider- ations, constraints and possibilities renders the task of address- ing and learning the detailed reactions of the citric acid cycle both more straightforward and more meaningful."

Dr Hanson offers his opinion that my scheme will serve to confuse students. As an alternative, he explains the oxidation of acetate to carbon dioxide by stating that the cycle incorporates "both carbons of acetate into a structure (enzyme bound oxalosuccinate) which allows two molecules of carbon dioxide to be liberated by two successive oxidative decarboxylations." In my opinion, this does not simplify matters for students and

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leaves the key question about the need for an initial conden- sation of acetate into a more complex molecule (citrate) completely unanswered.

Dr Hanson goes on: "At this stage in the cycle (succinyl CoA) the oxidation of the carbons of acetate is complete. It is irrelevant that, as shown by labelling studies, the carbons liberated as carbon dioxide are not actually derived from acetate." I think that students will need to have achieved a degree of sophistication before they will find this, and the final section of Dr Hanson's rationale, a simpler aid to learning the cycle than my own offering.

Clearly, we can readily trade opinions without assisting students. I suggest that we leave them, and their teachers, to come to their own conclusions. If, as a result, they are prompted constructively to look at the reactions of the cycle in a slightly different way that aids the process of understanding the citric acid cycle, then I am sure that both our objectives will be fulfilled.

P D J Weitzman Cardiff Institute for Higher Education

PO Box 377 Llandaff Centre Western Avenue

Cardiff CF5 2SG, UK

Text Book Error: Threonine is ketogenic too

Dear Sir, Catabolism of carbon skeletons of t-ct amino acids is perhaps one of the most fascinating aspects of biochemistry. The carbon skeletons are convertible either to carbohydrate (glucogenic), fat (ketogenic) or both and accordingly a 'metabolic ' classification is presented as in the table.

Class I Glucogenic amino acids End product/s

Group I Alanine Pyruvate Cysteine/Cystine Glycine Hydroxyproline Serine Threonine

Group II Arginine ot-ketoglutarate Histidine Glutamate Proline

Group III Methionine succinyl CoA Valine

Group IV Aspartate Oxaloacetate

Class II Both gluco- and ketogenic amino acids

Isoleucine Succinyl CoA + acetyl CoA phenylalanine Fumarate + acetoacetyl CoA Tyrosine Fumarate + acetoacetyl CoA Tryptophan Pyruvate + acetoacetyl CoA

Class IH Ketogenic amino acids

Leucine acetyl CoA Lysine crotonyl CoA

B I O C H E M I C A L E D U C A T I O N 20(3) 1992