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Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase: a control enzyme in ketogenesis.
Biochem J. 1999 Mar 15; 338 (Pt 3):569-82.BJ

Abstract

Cytosolic and mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthases were first recognized as different chemical entities in 1975, when they were purified and characterized by Lane's group. Since then, the two enzymes have been studied extensively, one as a control site of the cholesterol biosynthetic pathway and the other as an important control site of ketogenesis. This review describes some key developments over the last 25 years that have led to our current understanding of the physiology of mitochondrial HMG-CoA synthase in the HMG-CoA pathway and in ketogenesis in the liver and small intestine of suckling animals. The enzyme is regulated by two systems: succinylation and desuccinylation in the short term, and transcriptional regulation in the long term. Both control mechanisms are influenced by nutritional and hormonal factors, which explains the incidence of ketogenesis in diabetes and starvation, during intense lipolysis, and in the foetal-neonatal and suckling-weaning transitions. The DNA-binding properties of the peroxisome-proliferator-activated receptor and other transcription factors on the nuclear-receptor-responsive element of the mitochondrial HMG-CoA synthase promoter have revealed how ketogenesis can be regulated by fatty acids. Finally, the expression of mitochondrial HMG-CoA synthase in the gonads and the correction of auxotrophy for mevalonate in cells deficient in cytosolic HMG-CoA synthase suggest that the mitochondrial enzyme may play a role in cholesterogenesis in gonadal and other tissues.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, School of Pharmacy, University of Barcelona, Av/ Diagonal 643, 08028 Barcelona, Spain. hegardt@farmacia.far.ub.es

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

10051425

Citation

Hegardt, F G.. "Mitochondrial 3-hydroxy-3-methylglutaryl-CoA Synthase: a Control Enzyme in Ketogenesis." The Biochemical Journal, vol. 338 (Pt 3), 1999, pp. 569-82.
Hegardt FG. Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase: a control enzyme in ketogenesis. Biochem J. 1999;338 (Pt 3):569-82.
Hegardt, F. G. (1999). Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase: a control enzyme in ketogenesis. The Biochemical Journal, 338 (Pt 3), 569-82.
Hegardt FG. Mitochondrial 3-hydroxy-3-methylglutaryl-CoA Synthase: a Control Enzyme in Ketogenesis. Biochem J. 1999 Mar 15;338 (Pt 3):569-82. PubMed PMID: 10051425.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase: a control enzyme in ketogenesis. A1 - Hegardt,F G, PY - 1999/3/3/pubmed PY - 1999/3/3/medline PY - 1999/3/3/entrez SP - 569 EP - 82 JF - The Biochemical journal JO - Biochem J VL - 338 (Pt 3) N2 - Cytosolic and mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthases were first recognized as different chemical entities in 1975, when they were purified and characterized by Lane's group. Since then, the two enzymes have been studied extensively, one as a control site of the cholesterol biosynthetic pathway and the other as an important control site of ketogenesis. This review describes some key developments over the last 25 years that have led to our current understanding of the physiology of mitochondrial HMG-CoA synthase in the HMG-CoA pathway and in ketogenesis in the liver and small intestine of suckling animals. The enzyme is regulated by two systems: succinylation and desuccinylation in the short term, and transcriptional regulation in the long term. Both control mechanisms are influenced by nutritional and hormonal factors, which explains the incidence of ketogenesis in diabetes and starvation, during intense lipolysis, and in the foetal-neonatal and suckling-weaning transitions. The DNA-binding properties of the peroxisome-proliferator-activated receptor and other transcription factors on the nuclear-receptor-responsive element of the mitochondrial HMG-CoA synthase promoter have revealed how ketogenesis can be regulated by fatty acids. Finally, the expression of mitochondrial HMG-CoA synthase in the gonads and the correction of auxotrophy for mevalonate in cells deficient in cytosolic HMG-CoA synthase suggest that the mitochondrial enzyme may play a role in cholesterogenesis in gonadal and other tissues. SN - 0264-6021 UR - https://www.unboundmedicine.com/medline/citation/10051425/Mitochondrial_3_hydroxy_3_methylglutaryl_CoA_synthase:_a_control_enzyme_in_ketogenesis_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/10051425/ DB - PRIME DP - Unbound Medicine ER -