Biochemistry: The Chemical Reactions of Living Cells, Volume 2 - D. Metzler 1980

Coenzymes: Specialized Natural Reagents
Lipoic Acid and the Oxidative Decarboxylation of α-Keto Acids
Pyruvate-Formate-Lyase Reaction

Anaerobic conversion of Pyruvate to formate and acetyl-CoA [equation (8-68)]

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plays a crucial role in the METABOLISM/26.html">Energy Metabolism of many Cells. This reaction requires no external oxidant, and Lipoic Acid is apparently not involved. The reaction is sometimes referred to as "phosphoroclastic" on the grounds that the acetyl-CoA product typically reacts further with phosphate to yield acetyl phosphate (Fig. 8-19). The latter subsequently transfers its phosphate group to ADP to form ATP.

FIG. 8-19. Two systems of Oxidative Decarboxylation of α-keto acids and "substrate-level" phosphorylation. To calculate The values of ∆G' shown in the figure, the value of ∆G' for the synthesis of ATP^4- from ADP^3- and НРО₃^- was assumed to be 34.5 kJ∙mol^-1.

The Mechanism of pyruvate Cleavage according to equation (8-68) is not yet fully understood. Thiamine diphosphate is not involved in the reaction [14-6, 147], and free СО₂ is not an intermediate [148]. It is possible that a certain intermediate electron carrier re-reduces the carboxyl group of pyruvate to form a thioester intermediate. Then, following the Cleavage of the C—C bond, the cofactor might oxidize the active aldehyde form (possibly a thiamine-bound adduct), restoring the carrier to its initial reduced form. The unstable enzyme system required for this process consists of multiple Proteins; some of them apparently play an auxiliary role, ensuring the proper "activation" of the lyase. Both the clostridial enzyme and the E. coli enzyme are activated by reducing agents, including reducedferredoxin or reduced flavodoxin and S-adenosylmethionine [148] [Structure given in equation (7-1)], which may act as an allosteric effector. The inactive and active forms can be interconverted via alkylation and reduction [149].

It should be borne in mind that while E. coli cultured under anaerobic conditions produces pyruvate-formate lyase, in the presence of air the same bacterium synthesizes the lipoic acid-containing pyruvate dehydrogenase complex (Fig. 8-17).

In the cells of many Bacteria, including E. coli, formic acid produced according to equations (8-67) can be reversibly converted into СО₂ and hydrogen by the action of a two-enzyme formate-hydrogen lyase system (Chapter 9, Section E, 2).