Diabetes and the control of pyruvate dehydrogenase in rat heart mitochondria by concentration ratios of adenosine triphosphate/adenosine diphosphate, of reduced/oxidized nicotinamide-adenine dinucleotide and of acetyl-coenzyme A/coenzyme A.

The Biochemical journal ·Vol. 164 ·No. 3 ·1977-06-15 ·Pages 509-19

Kerbey AL, Radcliffe PM, Randle PJ

Abstract

1. The proportion of active (dephosphorylated) pyruvate dehydrogenase in rat heart mitochondria was correlated with total concentration ratios of ATP/ADP, NADH/NAD+ and acetyl-CoA/CoA. These metabolites were measured with ATP-dependent and NADH-dependent luciferases. 2. Increase in the concentration ratio of NADH/NAD+ at constant [ATP]/[ADP] and [acetyl-CoA]/[CoA] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between mitochondria incubated with 0.4mM- or 1mM-succinate and mitochondria incubated with 0.4mM-succinate+/-rotenone. 3. Increase in the concentration ratio acetyl-CoA/CoA at constant [ATP]/[ADP] and [NADH][NAD+] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between incubations in 50 micrometer-palmitotoyl-L-carnitine and in 250 micrometer-2-oxoglutarate +50 micrometer-L-malate. 4. These findings are consistent with activation of the pyruvate dehydrogenase kinase reaction by high ratios of [NADH]/[NAD+] and of [acetyl-CoA]/[CoA]. 5. Comparison between mitochondria from hearts of diabetic and non-diabetic rats shows that phosphorylation and inactivation of pyruvate dehydrogenase is enhanced in alloxan-diabetes by some factor other than concentration ratios of ATP/ADP, NADH/NAD+ or acetyl-CoA/CoA.

MeSH Terms

Acetyl Coenzyme A/metabolism Adenosine Diphosphate/metabolism Adenosine Triphosphate/metabolism Animals Coenzyme A/metabolism Diabetes Mellitus/enzymology,metabolism Male Mitochondria, Muscle/enzymology,metabolism Myocardium/enzymology,metabolism NAD/metabolism Pyruvate Dehydrogenase Complex/metabolism Rats

Chemicals

Pyruvate Dehydrogenase Complex NAD Adenosine Diphosphate Acetyl Coenzyme A Adenosine Triphosphate Coenzyme A

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

Kerbey A L

Radcliffe P M

Randle P J

References (25)

25 references, click to expand

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Article Info

Journal

The Biochemical journal

Abbr.

Biochem J

ISSN

0264-6021

DOI

10.1042/bj1640509

Published

1977-06-15

Pages

509-19

Language

English

Region

England

NLM ID

2984726R

PMCID

PMC1164826

Subset

External Links

PubMed source DOI: 10.1042/bj1640509 PMC Full Text View journal details

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Diabetes and the control of pyruvate dehydrogenase in rat heart mitochondria by concentration ratios of adenosine triphosphate/adenosine diphosphate, of reduced/oxidized nicotinamide-adenine dinucleotide and of acetyl-coenzyme A/coenzyme A.

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