Pyruvate dehydrogenase, substrate specificity and product inhibition.

1 Studies with intact mitochondria and with soluble pyruvate dehydrogenase indicate that pyruvate and α-ketobutyrate are oxidized by the same enzyme (pyruvate dehydrogenase), while α-ketovalerate is oxidized by a different enzyme. 2 Pyruvate and α-ketobutyrate have about the same affinity for the enzyme, but pyruvate is oxidized at a much higher rate. 3 Acetyl-CoA and propionyl-CoA both behave as competitive inhibitors to CoA. The Ki for both is slightly higher than the Km for CoA. Accordingly the enzyme is only moderately inhibited by a high acetyl-CoA/CoA ratio. 4 NADH behaves mainly as a competitive inhibitor to NAD. The Ki is significantly lower than the Km for NAD. Accordingly the enzyme is strongly inhibited by a high NADH/NAD ratio. 5 The significance of these properties of the enzyme for the regulation of the activity of pyruvate dehydrogenase in vivo is discussed.

[1]  U. Henning,et al.  Regulation of pyruvate dehydrogenase activity in Escherichia coli K12. , 1966, Biochimica et biophysica acta.

[2]  L. Reed,et al.  Lipoic acid activation of the alpha-ketobutyrate oxidation system in cell-free extracts of Streptococcus faecalis. , 1955, Biochimica et biophysica acta.

[3]  J. Bremer,et al.  Acyl coenzyme A as an intermediate in the mitochondrial acylation of carnitine by α-keto acids , 1963 .

[4]  S. Angielski,et al.  Tissue Content of Citrate and Citrate-cleavage Enzyme Activity during Starvation and Refeeding , 1967, Nature.

[5]  T. Bøhmer.  The formation of propionylcarnitine in isolated rat liver mitochondria. , 1968, Biochimica et Biophysica Acta.

[6]  L. Reed,et al.  Studies on a lipoic acid-activating system. , 1958, The Journal of biological chemistry.

[7]  J. Bremer,et al.  Propionylcarnitine. Physiological variations in vivo. , 1968, Biochimica et biophysica acta.

[8]  R. Koeppe,et al.  Some factors affecting routes of pyruvate metabolism in rats. , 1959, The Journal of biological chemistry.

[9]  R. M. Oliver,et al.  Alpha-Keto acid dehydrogenase complexes, V. Macromolecular organization of pyruvate and alpha-ketoglutarate dehydrogenase complexes isolated from beef kidney mitochondria. , 1966, Proceedings of the National Academy of Sciences of the United States of America.

[10]  C. Silbert,et al.  Inhibition by citrate of pyruvate dehydrogenase in rat liver mitochondria. , 1968, Biochemical and biophysical research communications.

[11]  O. Wieland,et al.  Suppression of pyruvate oxidation in liver mitochondria in the presence of long-chain fatty acid. , 1968, European journal of biochemistry.

[12]  L. Reed,et al.  Regulatory properties of pyruvate dehydrogenase from Escherichia coli. , 1968, Biochemical and biophysical research communications.

[13]  E. Newsholme,et al.  The effects of starvation and alloxan-diabetes on the contents of citrate and other metabolic intermediates in rat liver. , 1968, The Biochemical journal.

[14]  H. Krebs,et al.  The redox state of free nicotinamide-adenine dinucleotide in the cytoplasm and mitochondria of rat liver. , 1967, The Biochemical journal.

[15]  J. Bremer,et al.  The mechanism of substrate inhibition of palmityl coenzyme A:carnitine palmityltransferase by palmityl coenzyme A. , 1967, The Journal of biological chemistry.

[16]  D. Haft.  EVIDENCE FOR INHIBITION OF ACETYL-COENZYME A FORMATION FROM PYRUVATE IN DIABETIC RAT LIVER. , 1964, Biochimica et biophysica acta.

[17]  N. Lavintman.  The formation of branched glucans in sweet corn. , 1966, Archives of biochemistry and biophysics.