Krebs cycle enzymes from livers of old mice are differentially regulated by caloric restriction

Kevork Hagopian, Jon J Ramsey, Richard Weindruch

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Krebs cycle enzyme activities and levels of five metabolites were determined from livers of old mice (30 months) maintained either on control or on long-term caloric restriction (CR) diets (28 months). In CR mice, the cycle was divided into two major blocks, the first containing citrate synthase, aconitase and NAD-dependent isocitrate dehydrogenase which showed decreased activities, while the second block, containing the remaining enzymes, displayed increased activity (except for fumarase, which was unchanged). CR also resulted in decreased levels of citrate, glutamate and α-ketoglutarate, increased levels of malate, and unchanged levels of aspartate. The α-ketoglutarate/ glutamate and malate/α-ketoglutarate ratios were higher in CR, in parallel with previously reported increases with CR in pyruvate carboxylase activity and glucagon levels, respectively. The results indicate that long-term CR induces a differential regulation of Krebs cycle in old mice and this regulation may be the result of changes in gene expression levels, as well as a complex interplay between enzymes, hormones and other effectors. Truncation of Krebs cycle by CR may be an important adaptation to utilize available substrates for the gluconeogenesis necessary to sustain glycolytic tissues, such as brain.

Original languageEnglish (US)
Pages (from-to)1145-1154
Number of pages10
JournalExperimental Gerontology
Volume39
Issue number8
DOIs
StatePublished - Aug 2004

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Caloric Restriction
Citric Acid Cycle
Liver
Enzymes
Glutamic Acid
Fumarate Hydratase
Pyruvate Carboxylase
Aconitate Hydratase
Isocitrate Dehydrogenase
Citrate (si)-Synthase
Gluconeogenesis
Enzyme activity
Nutrition
Metabolites
Glucagon
Gene expression
Aspartic Acid
Citric Acid
NAD
Brain

Keywords

  • α-KGDH, α-ketoglutarate dehydrogenase complex
  • Aco, aconitase
  • Aging
  • Caloric restriction
  • CR, caloric restriction
  • CS, citrate synthase
  • Krebs cycle enzymes
  • Liver
  • NAD-ICDH, NAD-linked isocitrate dehydrogenase
  • STK, succinyl-CoA thiokinase

ASJC Scopus subject areas

  • Aging
  • Medicine(all)

Cite this

Krebs cycle enzymes from livers of old mice are differentially regulated by caloric restriction. / Hagopian, Kevork; Ramsey, Jon J; Weindruch, Richard.

In: Experimental Gerontology, Vol. 39, No. 8, 08.2004, p. 1145-1154.

Research output: Contribution to journalArticle

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