The metabolic effects of dichloroacetate

David Crabb, Emily A. Yount, Robert Harris

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

Dichloroacetate activates the pyruvate dehydrogenase complex of many tissues by inhibiting the kinase responsible for phosphorylation and inactivation of the complex. Dichloroacetate also activates the myocardial branched-chain α-keto acid dehydrogenase complex but apparently not by direct inhibition of the analogous kinase. Oxalate and glyoxylate, metabolites of dichloroacetate, are responsible for some in vitro effects of dichloroacetate. Dichloroacetate stimulates leucine oxidation by isolated hepatocytes because glyoxylate transaminates with leucine. Dichloroacetate inhibits lactate gluconeogenesis by hepatocytes incubated in low bicarbonate buffer because oxalate inhibits pyruvate carboxylase under such conditions. In vivo, dichloroacetate decreases blood glucose by limiting the supply of gluconeogenic precursors to the liver. This effect is a consequence of pyruvate dehydrogenase activation in peripheral tissues. Dichloroacetate lowers blood cholesterol in hyperlipidemic patients by uncertain means. Dichloroacetate has been tried experimentally in treatment of diabetes, hypercholesterolemia, and hyperlactatemia, but it has neurotoxicity, can cause cataracts, and may be mutagenic.

Original languageEnglish
Pages (from-to)1024-1039
Number of pages16
JournalMetabolism: Clinical and Experimental
Volume30
Issue number10
DOIs
StatePublished - 1981

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Oxalates
Leucine
Hepatocytes
Phosphotransferases
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
Pyruvate Carboxylase
Pyruvate Dehydrogenase Complex
Gluconeogenesis
Bicarbonates
Hypercholesterolemia
Pyruvic Acid
Cataract
Blood Glucose
Lactic Acid
Buffers
Oxidoreductases
Cholesterol
Phosphorylation
Liver
glyoxylic acid

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

The metabolic effects of dichloroacetate. / Crabb, David; Yount, Emily A.; Harris, Robert.

In: Metabolism: Clinical and Experimental, Vol. 30, No. 10, 1981, p. 1024-1039.

Research output: Contribution to journalArticle

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