Control of hepatic mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase during the foetal/neonatal transition, suckling and weaning in the rat

Authors

  • Patti A. QUANT,

    Corresponding author
    1. Centre de Recherches sur la Nutrition du Centre National de la Recherche Scientifique, Meudon-Bellevue, France
    2. Department of Biochemistry, University of Cambridge, England
      Correspondence to P. A. Quant, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambidge CB2 1QW, England
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  • Danielle ROBIN,

    1. Centre de Recherches sur la Nutrition du Centre National de la Recherche Scientifique, Meudon-Bellevue, France
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  • Pierre ROBIN,

    1. Centre de Recherches sur la Nutrition du Centre National de la Recherche Scientifique, Meudon-Bellevue, France
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  • Pascal FERRE,

    1. Centre de Recherches sur la Nutrition du Centre National de la Recherche Scientifique, Meudon-Bellevue, France
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  • Martin D. BRAND,

    1. Department of Biochemistry, University of Cambridge, England
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  • Jean GIRARD

    1. Centre de Recherches sur la Nutrition du Centre National de la Recherche Scientifique, Meudon-Bellevue, France
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Correspondence to P. A. Quant, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambidge CB2 1QW, England

Abstract

  • 1We assayed active and total (i.e. active plus succinylated) 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase in mitochondria isolated from foetal, neonatal, suckling or weaned rats.
  • 2HMG-CoA synthase was substantially succinylated and inactivated in mitochondria isolated from termfoetal, (1-h-old, 6-h-old, 1-day-old) neonatal, suckling and high carbohydrate/low-fat (hc)-weaned rats. Succinylation of HMG-CoA synthase was very low in mitochondria isolated from the livers of foetal, 30-min-old neonatal and high-fat/carbohydrate-free (hf)-weaned rats.
  • 3There was a negative correlation between active HMG-CoA synthase and succinyl-CoA content in mitochondria isolated from term-foetal, suckling and hc-weaned rats.
  • 4Differences in active enzyme could not be entirely accounted for by differences in succinylation and inactivation of the synthase. Immunoassay confirmed that the absolute amounts of mitochondrial HMG-CoA synthase increased during the foetal/neonatal transition and decreased with hc weaning. The levels remained elevated with hf weaning.
  • 5From these data we propose that mitochondrial HMG-CoA synthase is controlled by two different mechanisms in young rats. Regulation by succinylation provides a mechanism for rapid modification of existing enzyme in response to changing metabolic states. Changes in the absolute amounts of HMG-CoA synthase provide a more long-term control in response to nutritional changes.
Abbreviations
hc

high carbohydrate/low fat

hf

high fat/carbohydrate free

HMG-CoA

3-hydroxy-3-methylglutaryl-CoA

RCR

respiratory control ratio

Enzymes
 

3-Hydroxy-3-methylglutaryl-CoA synthase (EC 4.1.3.5)

 

phosphotransacetylase (EC 2.3.1.8)

 

carnitine palmitoyl-transferase I (EC 2.3.1.21)

Ancillary