Pyruvate dehydrogenase regulation

Pyruvate Dehydrogenase Is Regulated by End-Product Inhibition Covalent Modification... 

Figure 17-6. Regulation of pyruvate dehydrogenase (PDH). Arrows with wavy shafts indicate allosteric effects. A Regulation by end-product inhibition. B Regulation by interconversion of active and inactive forms.

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

This chapter focuses on the developmental regulation of the pyruvate dehydrogenase complex (PDC). The PDC plays diverse and pivotal roles in the entry of glycolytically generated carbon into the TCA cycle in aerobic stages and the metabolism of mitochondrially generated pyruvate in anaerobic stages (Fig. 14.1). 

Fig. 14.2. Regulation of the pyruvate dehydrogenase complex (PDC) from adult A suum muscle. PDC, pyruvate dehydrogenase complex E1, pyruvate dehydrogenase subunit of the PDC PDK, pyruvate dehydrogenase kinase PDP, pyruvate dehydrogenase phosphatase.

Bowker-Kinley, M.M., Davis, W.I., Wu, P., Harris, R.A. and Popov, KM. (1998) Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex. Bio chemicalfournal 329, 191-196. 

Korotchkina, L.G. and Patel, M.S. (1995) Mutagenesis studies of the phosphorylation sites of recombinant human pyruvate dehydrogenase. Site-specific regulation. Journal of Biological Chemistry 270, 14297—14304. 

Rahmatullah, M. and Roche, T.E. (1987) The catalytic requirements for reduction and acetylation of protein X and the related regulation of various forms of resolved pyruvate dehydrogenase kinase. Journal of Biological Chemistry 262, 10265-10271. 

Song, H. and Komuniecki, R. (1994) Novel regulation of pyruvate dehydrogenase phosphatase purified from anaerobic muscle mitochondria of the adult parasitic nematode, Ascaris suum. Journal of Biological Chemistry 269, 31573-31578. 

Yang, D., Gong, X., Yakhnin, A. and Roche, T.E. (1998) Requirements for the adaptor protein role of dihydrolipoyl acetyltransferase in the up-regulated function of the pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase. Journal of Biological Chemistry 273, 14130-14137. 

The pyruvate dehydrogenase complex plays a key role in regulating oxidation of glucose 543... 

Coordinate Regulation of Pyruvate Carboxylase and Pyruvate Dehydrogenase by Acetyl CoA... 

The two major mitochondrial enzymes (Figure 1-14-5) that use pyruvate, pyruvate carboxylase and pyruvate dehydrogenase, are both regulated by acetyl CoA. This control is important in these contexts ... 

Figure 16.1 The glucose/fatty add cycle. The dotted Lines represent regulation. Glucose in adipose tissue produces glycerol 3-phosphate which enhances esterification of fatty acids, so that less are available for release. The effect is, therefore, tantamount to inhibition of lipolysis. Fatty acid oxidation inhibits pyruvate dehydrogenase, phosphofructokinase and glucose transport in muscle (Chapters 6 and 7) (Randle et al. 1963).

The most important factor in the regulation of the cycle is the NADH/NAD ratio. In addition to pyruvate dehydrogenase (PDH) and oxoglu-tarate dehydrogenase (ODH see p. 134), citrate synthase and isodtrate dehydrogenase are also inhibited by NAD deficiency or an excess of NADH+HT With the exception of isocitrate dehydrogenase, these enzymes are also subject to product inhibition by acetyl-CoA, suc-cinyl-CoA, or citrate. 

Covalent interconversion of enzymes is well established as a fundamental theme in metabolic regulation. The prototypic reversible interconverting systems include the sequence of phosphorylation/dephosphorylation steps in the activation of mammalian glycogen phosphorylase and pyruvate dehydrogenase as well as the nucleotidyla-tion/denucleotidylation using UTP and ATP in the bacterial glutamine synthetase cascade (see Fig. 1.). 

Hoshi, M. Takashima, A. Noguchi, K. Murayama, M. Sato, M. Kondo, S. Saitoh, Y. Ishiguro, K. Hoshino, T. Imahori, K. Regulation of mitochondrial pyruvate dehydrogenase activity by r protein kinase I/glycogen synthase kinase 3/1 in brain. Proc. Natl. Acad. Sci. USA, 93, 2719-2723 (1996)... 

Patel, M.S., Nalk, S., Wexler, I.D., Kerr, D.S. (1995) Gene regulation and genetic defects in the pyruvate dehydrogenase complex. J. Nutr. 125, 1753S-1757S. 

Production of Acetyl-CoA by the Pyruvate Dehydrogenase Complex Is Regulated by Allosteric and Covalent Mechanisms... 

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