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PMID: 6095807 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A re-evaluation of the role of mitochondrial pyruvate transport in the hormonal control of rat liver mitochondrial pyruvate metabolism.

The Biochemical journal ·Vol. 223 ·No. 3 ·1984-11-01 ·Pages 677-85

Halestrap AP, Armston AE

Abstract

The inhibitor of mitochondrial pyruvate transport alpha-cyano-beta-(1-phenylindol-3-yl)-acrylate was used to inhibit progressively pyruvate carboxylation by liver mitochondria from control and glucagon-treated rats. The data showed that, contrary to our previous conclusions [Halestrap (1978) Biochem. J. 172, 389-398], pyruvate transport could not regulate metabolism under these conditions. This was confirmed by measuring the intramitochondrial pyruvate concentration, which almost equilibrated with the extramitochondrial pyruvate concentration in control mitochondria, but was significantly decreased in mitochondria from glucagon-treated rats, where rates of pyruvate metabolism were elevated. Computer-simulation studies explain how this is compatible with linear Dixon plots of the inhibition of pyruvate metabolism by alpha-cyano-4-hydroxycinnamate. Parallel measurements of the mitochondrial membrane potential by using [3H]triphenylmethylphosphonium ions showed that it was elevated by about 3 mV after pretreatment of rats with both glucagon and phenylephrine. There was no significant change in the transmembrane pH gradient. It is shown that the increase in pyruvate metabolism can be explained by a stimulation of the respiratory chain, producing an elevation in the protonmotive force and a consequent rise in the intramitochondrial ATP/ADP ratio, which in turn increases pyruvate carboxylase activity. Mild inhibition of the respiratory chain with Amytal reversed the effects of hormone treatment on mitochondrial pyruvate metabolism and ATP concentrations, but not on citrulline synthesis. The significance of these observations for the hormonal regulation of gluconeogenesis from L-lactate in vivo is discussed.

MeSH Terms
Acrylates/pharmacology Adenosine Triphosphate/metabolism Animals Biological Transport/drug effects Coumaric Acids/pharmacology Female Glucagon/pharmacology In Vitro Techniques Mitochondria, Liver/drug effects,metabolism Oxygen Consumption/drug effects Protons Pyruvates/metabolism Pyruvic Acid Rats Rats, Inbred Strains
Chemicals
Acrylates Coumaric Acids Protons Pyruvates alpha-cyano-4-hydroxycinnamate 2-cyano-3-(1-phenylindol-3-yl)acrylate Pyruvic Acid Adenosine Triphosphate Glucagon
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Halestrap A P
Armston A E
References (57)
57 references, click to expand
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj2230677
Published
1984-11-01
Pages
677-85
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1144351
Subset
IM
External Links
PubMed source DOI: 10.1042/bj2230677 PMC Full Text View journal details
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