Pyruvate dehydrogenase multienzyme

Behai RH et al Regulation of the pyruvate dehydrogenase multienzyme complex. Annu Rev Nutr 1993 13 497. 

Packman, L.C., and Perham, R.N. (1982) Quaternary structure of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus studied by a new reversible cross-linking procedure with bis(imidoesters). Biochemistry 21, 5171-5175. 

A. P. Zeng, J. Modak, and W. D. Deckwer, Nonlinear dynamics of eucaryotic pyruvate dehydrogenase multienzyme complex Decarboxylation rate, oscillations, and multiplicity. Biotechnol. Prog. 18(6), 1265 1276 (2002). 

Bocanegra, J. H. A.,Scrutton,N. S. Perham, R. N. (1993). Creation of an NADP-dependent pyruvate dehydrogenase multienzyme complex by protein engineering. Biochemistry, 32, 2737-40. 

That there is an enamine-like intermediate in all thiamin diphosphate-dependent enzymatic pathways has been suggested for many years, although the issue is still sometimes clouded by the observation that the C2a-protonated form, the C2a-hydro-xyethylThDP when added to oxidases such as pyruvate oxidase (POX) and the pyruvate dehydrogenase multienzyme complex (PDHc), will undergo oxidation. 

GJ. Domingo, H.J. Chauhan, LA. Lessard, C. Fuller, and R.N. Perham. 1999. Self-assembly and catalytic activity of the pyruvate dehydrogenase multienzyme complex from Bacillus stearothermophilus Eur. J. Biochem. 266 1136-1146. (PubMed)... 

The deprotonation and addition of a base to thiazolium salts are combined to produce an acyl carbanion equivalent (an active aldehyde) [363, 364], which is known to play an essential role in catalysis of the thiamine diphosphate (ThDP) coenzyme [365, 366]. The active aldehyde in ThDP dependent enzymes has the ability to mediate an efScient electron transfer to various physiological electron acceptors, such as lipoamide in pyruvate dehydrogenase multienzyme complex [367], flavin adenine dinucleotide (FAD) in pyruvate oxidase [368] and Fc4S4 cluster in pyruvate ferredoxin oxidoreductase [369]. 

Under aerobic conditions, pyruvate can be oxidatively decarboxylated via the pyruvate dehydrogenase multienzyme complex to yield acetyl-CoA, which can then be completely oxidised via the citric acid cycle (Fig. 2). In eubacteria growing anaerobically, pyruvate is metabolised fermentatively, thus serving as an electron sink for reducing equivalents generated in its formation from glucose. The diverse array of possible fermentative reactions from pyruvate is reviewed in [5]. 

Inhibition of pyruvate dehydrogenase multienzyme complex (PD) from E. coli with radiolabelled bifunctional arsenoxide... 

Jones, D. D., Horne, H. J., Reche, P. A., and Perham, R. N. 2000. Structural determinants of post-translational modification and catalytic specificity for the lipoyi domains of the pyruvate dehydrogenase multienzyme complex of Escherichia coli. J. Mot. Biol. 295 289-306. 

Deprotonation Rate of the C2-H of Thiamin Diphosphate in the Pyruvate Dehydrogenase Multienzyme Complex from Escherichia coli... 

Akiyama, S. K., Hammes, G. G. (1980), Elementary steps in the reaction mechanism of the pyruvate dehydrogenase multienzyme complex from Escherichia coli kinetics of acetylation and deacetylation, Biochemistry 19, 4208-4213. 

The El component of pyruvate dehydrogenase multienzyme complex catalyses the decarboxylation of pyruvate and transfer of the acyl group to the lipoyl group of the E2 component. 

Fries, M.et al. (2007) Distinct modes of recognition of the lipoyl domain as substrate by the El and E3 components of the pyruvate dehydrogenase multienzyme complex. J. Mol. Biol. 366, 132-139... 

Mattevi A, De Kok A, Perham RN (1992) The pyruvate dehydrogenase multienzyme complex. Curr Opin Struct Biol 2 877-887... 

Henderson CE, Perham RN (1980) Purificaton of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus and resolution of its foirr component polypeptides. Biochem J 189 161—172... 

Seifert F, Golblk R, Brauer J et al (2006) Direct kinetic evidence for half-of-the-sites reactivity in the El component of the human pyruvate dehydrogenase multienzyme complex through alternating sites cofactor activation. Biochemistry 45 12775-12785... 

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