Hmgcs2

Summary

Gene Symbol: Hmgcs2
Description: 3-hydroxy-3-methylglutaryl-CoA synthase 2
Alias: Hmgcs1, Mt3h3mg, hydroxymethylglutaryl-CoA synthase, mitochondrial, 3-hydroxy-3-methylglutary-Coenzyme A synthase 2, 3-hydroxy-3-methylglutaryl coenzyme A synthase, 3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial), 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 2 (mitochondrial), HMG-CoA synthase, hydroxymethylglutaryl-CoA synthase 2
Species: rat
Products:     Hmgcs2

Top Publications

  1. Quant P, Tubbs P, Brand M. Glucagon activates mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in vivo by decreasing the extent of succinylation of the enzyme. Eur J Biochem. 1990;187:169-74 pubmed
    ..This may be an important control mechanism in ketogenesis. ..
  2. Rardin M, He W, Nishida Y, Newman J, Carrico C, Danielson S, et al. SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks. Cell Metab. 2013;18:920-33 pubmed publisher
    ..SIRT5 regulates succinylation of the rate-limiting ketogenic enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) both in vivo and in vitro...
  3. Satoh M, Haruta Satoh E, Yamada M, Kado S, Nomura F. Overexpression of hydroxymethylglutaryl CoA synthase 2 and 2,4-dienoyl-CoA reductase in rat pancreas following chronic alcohol consumption. Pancreas. 2013;42:475-82 pubmed publisher
    ..The 2 up-regulated proteins were identified as 2,4-dienoyl-CoA reductase and hydroxymethylglutaryl-CoA synthase (HMGCS2)...
  4. de Boer V, van Schothorst E, Dihal A, van der Woude H, Arts I, Rietjens I, et al. Chronic quercetin exposure affects fatty acid catabolism in rat lung. Cell Mol Life Sci. 2006;63:2847-58 pubmed
    ..Up-regulation of genes (Hmgcs2, Ech1, Acox1, Pcca, Lpl and Acaa2) was verified and confirmed by quantitative real time PCR...
  5. Moral R, Solanas M, Manzanares E, Haro D, Escrich E. Influence of DMBA-induced mammary cancer on the liver CPT I, mit HMG-CoA synthase and PPARalpha mRNA expression in rats fed a low or high corn oil diet. Int J Mol Med. 2004;14:283-7 pubmed
    ..This effect of the cancer state could be related to tumor aggressiveness and suggest a preferential redirection of long-chain fatty acids into energetic and specific pathways of the cancer cells. ..
  6. Steiner S, Gatlin C, Lennon J, McGrath A, Seonarain M, Makusky A, et al. Cholesterol biosynthesis regulation and protein changes in rat liver following treatment with fluvastatin. Toxicol Lett. 2001;120:369-77 pubmed
  7. Madsen L, Garras A, Asins G, Serra D, Hegardt F, Berge R. Mitochondrial 3-hydroxy-3-methylglutaryl coenzyme A synthase and carnitine palmitoyltransferase II as potential control sites for ketogenesis during mitochondrion and peroxisome proliferation. Biochem Pharmacol. 1999;57:1011-9 pubmed
    ..Under these conditions, the regulation of ketogenesis may be shifted to step(s) beyond CPT-I. This opens the possibility that mitochondrial HMG-CoA synthase and CPT-II retain some control of ketone body formation. ..
  8. López Barahona M, Iglesias T, Garcia Higuera I, Mayor F, Zaballos A, Bernal J, et al. Post-transcriptional induction of beta 1-adrenergic receptor by retinoic acid, but not triiodothyronine, in C6 glioma cells expressing thyroid hormone receptors. Eur J Endocrinol. 1996;135:709-15 pubmed
    ..We conclude that lack of responsiveness of the beta 1-AR gene in C6 cells to T3 is not due to high expression of c-erbA alpha 2 but to undefined cell-specific factors. ..
  9. Valera A, Rodriguez Gil J, Bosch F. Vanadate treatment restores the expression of genes for key enzymes in the glucose and ketone bodies metabolism in the liver of diabetic rats. J Clin Invest. 1993;92:4-11 pubmed
    ..All of these results suggest that the regulation of the expression of genes involved in the glucose and ketone bodies metabolism could be a key step in the normalization process induced by vanadate administration to diabetic rats. ..

Scientific Experts

More Information

Publications40

  1. Ness G, Zhao Z, Keller R. Effect of squalene synthase inhibition on the expression of hepatic cholesterol biosynthetic enzymes, LDL receptor, and cholesterol 7 alpha hydroxylase. Arch Biochem Biophys. 1994;311:277-85 pubmed
    ..The increase in HMG-CoA reductase gene expression was closely related to the degree of inhibition of cholesterol synthesis caused by zaragozic acid A. ..
  2. Thumelin S, Kohl C, Girard J, Pegorier J. Atypical expression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in subcutaneous adipose tissue of male rats. J Lipid Res. 1999;40:1071-7 pubmed
    ..Interestingly, FAS and CCE mRNAs co-segregate with mtHMG-CoA synthase mRNA. The possible physiological relevance of such atypical expression of mtHMG-CoA synthase is discussed. ..
  3. Lang C, Berardi S, Schafer M, Serra D, Hegardt F, Krahenbuhl L, et al. Impaired ketogenesis is a major mechanism for disturbed hepatic fatty acid metabolism in rats with long-term cholestasis and after relief of biliary obstruction. J Hepatol. 2002;37:564-71 pubmed
    ..Rats with long-term cholestasis have reduced ketosis of unknown origin...
  4. Cherbuy C, Andrieux C, Honvo Houeto E, Thomas M, Ide C, Druesne N, et al. Expression of mitochondrial HMGCoA synthase and glutaminase in the colonic mucosa is modulated by bacterial species. Eur J Biochem. 2004;271:87-95 pubmed
    ..These modifications in gene expression by butyrate in vivo seem unrelated to a modification of histone acetylation. ..
  5. Kiyosawa N, Tanaka K, Hirao J, Ito K, Niino N, Sakuma K, et al. Molecular mechanism investigation of phenobarbital-induced serum cholesterol elevation in rat livers by microarray analysis. Arch Toxicol. 2004;78:435-42 pubmed
    ..Thus, serum chemistry and microarray results suggested that repeated PB treatments induced cholesterogenesis in rat livers, which may have contributed to the elevation of the serum total cholesterol concentration. ..
  6. König B, Eder K. Differential action of 13-HPODE on PPARalpha downstream genes in rat Fao and human HepG2 hepatoma cell lines. J Nutr Biochem. 2006;17:410-8 pubmed
    ..Consequently, cellular and secreted triglyceride levels were not changed after incubation of HepG2 cells with 13-HPODE. In conclusion, this study shows that 13-HPODE activates PPARalpha in rat Fao but not in human HepG2 hepatoma cells. ..
  7. Kostiuk M, Corvi M, Keller B, Plummer G, Prescher J, Hangauer M, et al. Identification of palmitoylated mitochondrial proteins using a bio-orthogonal azido-palmitate analogue. FASEB J. 2008;22:721-32 pubmed
    ..We postulate that covalent modification and perhaps inhibition of various mitochondrial enzymes by palmitoyl-CoA could lead to the metabolic impairments found in obesity-related diseases. ..
  8. Wang F, Xiang H, Fischer G, Liu Z, Dupont M, Hogan Q, et al. HMG-CoA synthase isoenzymes 1 and 2 localize to satellite glial cells in dorsal root ganglia and are differentially regulated by peripheral nerve injury. Brain Res. 2016;1652:62-70 pubmed publisher
    ..report, we present evidence that the 3-hydroxy-3-methylglutaryl coenzyme A synthase isoenzymes 1 and 2 (HMGCS1 and HMGCS2) are abundantly expressed in SGCs...
  9. Serra D, Bellido D, Asins G, Arias G, Vilaro S, Hegardt F. The expression of mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme-A synthase in neonatal rat intestine and liver is under transcriptional control. Eur J Biochem. 1996;237:16-24 pubmed
  10. Cullingford T, Bhakoo K, Clark J. Hormonal regulation of the mRNA encoding the ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in neonatal primary cultures of cortical astrocytes and meningeal fibroblasts. J Neurochem. 1998;71:1804-12 pubmed
  11. Patel T, Clark J. Acetoacetate metabolism in rat brain. Development of acetoacetyl-coenzyme A deacylase and 3-hydroxy-3-methylglutaryl-coenzyme A synthase. Biochem J. 1978;176:951-8 pubmed
    ..The cytosolic enzyme correspondingly falls to approx. 40% of the total. 4. The role of the acetoacetyl-CoA deacylase in providing cytosolic acetoacetate for biosynthetic activities in the developing brain is discussed. ..
  12. Rodriguez J, Gil Gomez G, Hegardt F, Haro D. Peroxisome proliferator-activated receptor mediates induction of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene by fatty acids. J Biol Chem. 1994;269:18767-72 pubmed
  13. Thumelin S, Forestier M, Girard J, Pegorier J. Developmental changes in mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene expression in rat liver, intestine and kidney. Biochem J. 1993;292 ( Pt 2):493-6 pubmed
    ..When HC-weaned rats were fed on a HF-diet for a week, HMG-CoA synthase mRNA was re-induced in the intestine and the kidney. The role of hormones and nutrients in the regulation of HMG-CoA synthase gene expression is discussed. ..
  14. Ayte J, Gil Gomez G, Haro D, Marrero P, Hegardt F. Rat mitochondrial and cytosolic 3-hydroxy-3-methylglutaryl-CoA synthases are encoded by two different genes. Proc Natl Acad Sci U S A. 1990;87:3874-8 pubmed
    ..4 kilobases for the cytosolic enzyme), and the different expression pattern shown in RNA blot experiments suggest the presence of two HMG-CoA synthase genes, one for the cytosolic and another for the mitochondrial enzyme. ..
  15. Gil Gomez G, Ayte J, Hegardt F. The rat mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme-A-synthase gene contains elements that mediate its multihormonal regulation and tissue specificity. Eur J Biochem. 1993;213:773-9 pubmed
    ..Furthermore, the presence in the mitochondrial HMG-CoA-synthase promoter of cis-elements, responsible for the multihormonal regulation of transcription, is supported by transient transfection experiments. ..
  16. Yi W, Fu P, Fan Z, Aso H, Tian C, Meng Y, et al. Mitochondrial HMG-CoA synthase partially contributes to antioxidant protection in the kidney of stroke-prone spontaneously hypertensive rats. Nutrition. 2010;26:1176-80 pubmed publisher
    ..We explored the role of renal mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (HMGCS2) expression, a key control site of ketogenesis, in stroke-prone spontaneously hypertensive rats (SHRSPs) and their ..
  17. Ayte J, Gil Gomez G, Hegardt F. Methylation of the regulatory region of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene leads to its transcriptional inactivation. Biochem J. 1993;295 ( Pt 3):807-12 pubmed
    ..These results point to methylation as one of the regulatory mechanisms that operate on the mitochondrial HMG-CoA synthase gene. ..
  18. Carlsson L, Linden D, Jalouli M, Oscarsson J. Effects of fatty acids and growth hormone on liver fatty acid binding protein and PPARalpha in rat liver. Am J Physiol Endocrinol Metab. 2001;281:E772-81 pubmed
    ..Moreover, GH has different effects on PPARalpha-responsive genes and does not counteract the effect of LCFA on the expression of these gene products...
  19. Newsholme S, Maleeff B, Steiner S, Anderson N, Schwartz L. Two-dimensional electrophoresis of liver proteins: characterization of a drug-induced hepatomegaly in rats. Electrophoresis. 2000;21:2122-8 pubmed
  20. Arias G, Asins G, Hegardt F, Serra D. The effect of fasting/refeeding and insulin treatment on the expression of the regulatory genes of ketogenesis in intestine and liver of suckling rats. Arch Biochem Biophys. 1997;340:287-98 pubmed
    ..The different effects of refeeding and insulin treatment on the expression of both genes, on the ketogenic rate, and on ketone body concentrations are discussed. ..
  21. Cullingford T. The ketogenic diet; fatty acids, fatty acid-activated receptors and neurological disorders. Prostaglandins Leukot Essent Fatty Acids. 2004;70:253-64 pubmed
    ..Finally, the implications of the KD and activated brain PPARalpha will be discussed in the context of their potential involvement in a range of disorders of neuro-degeneration and neuro-inflammation. ..
  22. Sato T, Yamamoto H, Sawada N, Nashiki K, Tsuji M, Muto K, et al. Restraint stress alters the duodenal expression of genes important for lipid metabolism in rat. Toxicology. 2006;227:248-61 pubmed
    ..These results suggest that immobilization may alter lipid metabolism in the small intestine by modifying the expression of specific genes through which the small intestine may seek to protect itself from stress-induced damage. ..
  23. Du Z, Degrace P, Gresti J, Loreau O, Clouet P. Dissimilar properties of vaccenic versus elaidic acid in beta-oxidation activities and gene regulation in rat liver cells. Lipids. 2010;45:581-91 pubmed publisher
    ..In conclusion, the position and geometry of the double bonds in acyl chains are suggested to confer on vaccenic and elaidic acid specific biochemical properties that might differently affect their fates in tissues. ..
  24. Arias G, Asins G, Hegardt F, Serra D. The effect of dexamethasone treatment on the expression of the regulatory genes of ketogenesis in intestine and liver of suckling rats. Mol Cell Biochem. 1998;178:325-33 pubmed
    ..Two day treatment with dexamethasone produced no change in mRNA or activity levels for CPT I in liver or intestine. While mRNA levels for mit. HMG-CoA synthase changed little, the enzyme activity is decreased in both tissues. ..
  25. Pang Y, Cai Z, Rhodes P. Analysis of genes differentially expressed in astrocytes stimulated with lipopolysaccharide using cDNA arrays. Brain Res. 2001;914:15-22 pubmed
    ..These results indicate that both up-regulation of inflammatory cytokine expression and down-regulation of growth factor expression are probably involved in the response of astrocytes upon exposure to LPS. ..
  26. Serra D, Casals N, Asins G, Royo T, Ciudad C, Hegardt F. Regulation of mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase protein by starvation, fat feeding, and diabetes. Arch Biochem Biophys. 1993;307:40-5 pubmed
    ..All these results indicate that mitochondrial HMG-CoA synthase is a regulatory element in the ketogenic process. ..
  27. Patel V, Spencer C, Young T, Lively M, Cunningham C. Effects of 4-hydroxynonenal on mitochondrial 3-hydroxy-3-methylglutaryl (HMG-CoA) synthase. Free Radic Biol Med. 2007;43:1499-507 pubmed
    ..This study demonstrates that ethanol consumption increases the formation of a 4-HNE adduct with mitochondrial HMG-CoA synthase, which has the potential to inactivate the enzyme in situ. ..
  28. Asins G, Serra D, Hegardt F. The effect of etomoxir on the mRNA levels of enzymes involved in ketogenesis and cholesterogenesis in rat liver. Biochem Pharmacol. 1994;47:1373-9 pubmed
  29. Nadal A, Marrero P, Haro D. Down-regulation of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene by insulin: the role of the forkhead transcription factor FKHRL1. Biochem J. 2002;366:289-97 pubmed
    ..insulin rapidly inhibiting the expression of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase (HMGCS2) gene, which is a key control site of ketogenesis...
  30. Stocco C, Callegari E, Gibori G. Opposite effect of prolactin and prostaglandin F(2 alpha) on the expression of luteal genes as revealed by rat cDNA expression array. Endocrinology. 2001;142:4158-61 pubmed
  31. Hegardt F. Transcriptional regulation of mitochondrial HMG-CoA synthase in the control of ketogenesis. Biochimie. 1998;80:803-6 pubmed
    ..Other transcription factors such as chicken ovalbumin upstream promoter transcription factor (COUP-TF) and hepatocyte nuclear factor 4 (HNF-4) compete for the PPRE site, modulating the response of PPAR. ..