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Gene Review

HMGCS1  -  3-hydroxy-3-methylglutaryl-CoA synthase 1...

Homo sapiens

Synonyms: 3-hydroxy-3-methylglutaryl coenzyme A synthase, HMG-CoA synthase, HMGCS, Hydroxymethylglutaryl-CoA synthase, cytoplasmic
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Disease relevance of HMGCS1


High impact information on HMGCS1

  • SRE-1, a conditional enhancer in the promoters for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A synthase genes, increases transcription in the absence of sterols and is inactivated when sterols accumulate [6].
  • A cis-acting element necessary for sterol regulation, SRE-1, has previously been identified in the promoters of the low density lipoprotein receptor, hydroxymethylglutaryl (HMG)-CoA reductase, and HMG-CoA synthase genes [7].
  • The predominantly basic, hydrophobic, and hydroxylated nature of the residues of this sequence suggests that it is a leader peptide to target HMG-CoA synthase inside mitochondria [1].
  • (ii) A 19-amino acid sequence probably corresponding to the catalytic site is highly homologous (90%) to that reported for chicken liver mitochondrial HMG-CoA synthase [1].
  • 3-Hydroxy-3-methylglutaryl coenzyme A synthase (hydroxymethylglutaryl-CoA synthase, EC is a negatively regulated enzyme in the synthetic pathway for cholesterol, isopentenyl tRNA, and other isoprenoids [8].

Biological context of HMGCS1


Anatomical context of HMGCS1

  • The chromosomal localization of human HMG-CoA synthase was determined by examining a panel of human-mouse somatic cell hybrids with the rat cDNA probe [13].
  • Analysis of Western blot showed that the new cell line strongly expressed mitochondrial HMG-CoA synthase protein [14].
  • We and others have described mutant lines of Chinese hamster fibroblasts that are completely resistant to sterol-mediated repression of transcription of HMG-CoA reductase as well as two other sterol-regulated genes, HMG-CoA synthase and the low density lipoprotein (LDL) receptor [15].
  • We have investigated whether selected growth factors and hormones could increase 3-hydroxy-3-methylglutaryl coenzyme A synthase mRNA in keratinocytes [16].
  • We also analyze a new variation of PTS-2 sequences required to target HMG-CoA synthase and MPPD to peroxisomes [17].

Associations of HMGCS1 with chemical compounds


Regulatory relationships of HMGCS1


Other interactions of HMGCS1


Analytical, diagnostic and therapeutic context of HMGCS1


  1. Rat mitochondrial and cytosolic 3-hydroxy-3-methylglutaryl-CoA synthases are encoded by two different genes. Ayté, J., Gil-Gómez, G., Haro, D., Marrero, P.F., Hegardt, F.G. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  2. 3-hydroxy-3-methylglutaryl-coenzyme A synthase reaction intermediates: detection of a covalent tetrahedral adduct by differential isotope shift 13C nuclear magnetic resonance spectroscopy. Vinarov, D.A., Miziorko, H.M. Biochemistry (2000) [Pubmed]
  3. 3-Hydroxy-3-methylglutaryl-coenzyme A (CoA) synthase is involved in biosynthesis of isovaleryl-CoA in the myxobacterium Myxococcus xanthus during fruiting body formation. Bode, H.B., Ring, M.W., Schwär, G., Kroppenstedt, R.M., Kaiser, D., Müller, R. J. Bacteriol. (2006) [Pubmed]
  4. The molecular mechanism of the induction of the low density lipoprotein receptor by chenodeoxycholic acid in cultured human cells. Kawabe, Y., Shimokawa, T., Matsumoto, A., Honda, M., Wada, Y., Yazaki, Y., Endo, A., Itakura, H., Kodama, T. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  5. Cholesterol metabolism and colon cancer. Broitman, S.A., Cerda, S., Wilkinson, J. Progress in food & nutrition science. (1993) [Pubmed]
  6. SREBP-2, a second basic-helix-loop-helix-leucine zipper protein that stimulates transcription by binding to a sterol regulatory element. Hua, X., Yokoyama, C., Wu, J., Briggs, M.R., Brown, M.S., Goldstein, J.L., Wang, X. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  7. Common double- and single-stranded DNA binding factor for a sterol regulatory element. Stark, H.C., Weinberger, O., Weinberger, J. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  8. Optional exon in the 5'-untranslated region of 3-hydroxy-3-methylglutaryl coenzyme A synthase gene: conserved sequence and splicing pattern in humans and hamsters. Gil, G., Smith, J.R., Goldstein, J.L., Brown, M.S. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  9. Localization of the gene encoding 3-hydroxy-3-methylglutaryl-coenzyme A synthase to human chromosome 5. Leonard, S., Arbogast, D., Geyer, D., Jones, C., Sinensky, M. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  10. Transcriptional downregulation of sterol metabolism genes in murine liver exposed to acute hypobaric hypoxia. Dolt, K.S., Karar, J., Mishra, M.K., Salim, J., Kumar, R., Grover, S.K., Qadar Pasha, M.A. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  11. Autocrine platelet-derived growth factor-dependent gene expression in glioblastoma cells is mediated largely by activation of the transcription factor sterol regulatory element binding protein and is associated with altered genotype and patient survival in human brain tumors. Ma, D., Nutt, C.L., Shanehsaz, P., Peng, X., Louis, D.N., Kaetzel, D.M. Cancer Res. (2005) [Pubmed]
  12. Peroxisome proliferator-activated receptor mediates induction of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene by fatty acids. Rodríguez, J.C., Gil-Gómez, G., Hegardt, F.G., Haro, D. J. Biol. Chem. (1994) [Pubmed]
  13. Regulation of rat liver 3-hydroxy-3-methylglutaryl coenzyme A synthase and the chromosomal localization of the human gene. Mehrabian, M., Callaway, K.A., Clarke, C.F., Tanaka, R.D., Greenspan, M., Lusis, A.J., Sparkes, R.S., Mohandas, T., Edmond, J., Fogelman, A.M. J. Biol. Chem. (1986) [Pubmed]
  14. Transfection of the ketogenic mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase cDNA into Mev-1 cells corrects their auxotrophy for mevalonate. Ortiz, J.A., Gil-Gómez, G., Casaroli-Marano, R.P., Vilaró, S., Hegardt, F.G., Haro, D. J. Biol. Chem. (1994) [Pubmed]
  15. Genetic distinction between sterol-mediated transcriptional and posttranscriptional control of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Dawson, P.A., Metherall, J.E., Ridgway, N.D., Brown, M.S., Goldstein, J.L. J. Biol. Chem. (1991) [Pubmed]
  16. Regulation of HMG-CoA synthase and HMG-CoA reductase by insulin and epidermal growth factor in HaCaT keratinocytes. Harris, I.R., Höppner, H., Siefken, W., Farrell, A.M., Wittern, K.P. J. Invest. Dermatol. (2000) [Pubmed]
  17. Identification of peroxisomal targeting signals in cholesterol biosynthetic enzymes. AA-CoA thiolase, hmg-coa synthase, MPPD, and FPP synthase. Olivier, L.M., Kovacs, W., Masuda, K., Keller, G.A., Krisans, S.K. J. Lipid Res. (2000) [Pubmed]
  18. Isolation and sequence of the human farnesyl pyrophosphate synthetase cDNA. Coordinate regulation of the mRNAs for farnesyl pyrophosphate synthetase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and 3-hydroxy-3-methylglutaryl coenzyme A synthase by phorbol ester. Wilkin, D.J., Kutsunai, S.Y., Edwards, P.A. J. Biol. Chem. (1990) [Pubmed]
  19. Calcium ionophore treatment impairs the sterol-mediated suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, 3-hydroxy-3-methylglutaryl-coenzyme A synthase, and farnesyl diphosphate synthetase. Wilkin, D.J., Edwards, P.A. J. Biol. Chem. (1992) [Pubmed]
  20. Polyunsaturated fatty acids decrease expression of promoters with sterol regulatory elements by decreasing levels of mature sterol regulatory element-binding protein. Worgall, T.S., Sturley, S.L., Seo, T., Osborne, T.F., Deckelbaum, R.J. J. Biol. Chem. (1998) [Pubmed]
  21. Multiple DNA elements for sterol regulatory element-binding protein and NF-Y are responsible for sterol-regulated transcription of the genes for human 3-hydroxy-3-methylglutaryl coenzyme A synthase and squalene synthase. Inoue, J., Sato, R., Maeda, M. J. Biochem. (1998) [Pubmed]
  22. A critical role for cAMP response element-binding protein (CREB) as a Co-activator in sterol-regulated transcription of 3-hydroxy-3-methylglutaryl coenzyme A synthase promoter. Dooley, K.A., Bennett, M.K., Osborne, T.F. J. Biol. Chem. (1999) [Pubmed]
  23. Variations in the mRNA expression of inflammatory mediators, markers of differentiation and lipid-metabolizing enzymes caused by sodium lauryl sulphate in cultured human keratinocytes. Törmä, H., Geijer, S., Gester, T., Alpholm, K., Berne, B., Lindberg, M. Toxicology in vitro : an international journal published in association with BIBRA. (2006) [Pubmed]
  24. Cafestol, the cholesterol-raising factor in boiled coffee, suppresses bile acid synthesis by downregulation of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase in rat hepatocytes. Post, S.M., de Wit, E.C., Princen, H.M. Arterioscler. Thromb. Vasc. Biol. (1997) [Pubmed]
  25. Discordant regulation of proteins of cholesterol metabolism during the acute phase response. Feingold, K.R., Pollock, A.S., Moser, A.H., Shigenaga, J.K., Grunfeld, C. J. Lipid Res. (1995) [Pubmed]
  26. YY1 is a negative regulator of transcription of three sterol regulatory element-binding protein-responsive genes. Ericsson, J., Usheva, A., Edwards, P.A. J. Biol. Chem. (1999) [Pubmed]
  27. The inhibition of cytoplasmic acetoacetyl-CoA thiolase by a triyne carbonate (L-660, 631). Greenspan, M.D., Yudkovitz, J.B., Chen, J.S., Hanf, D.P., Chang, M.N., Chiang, P.Y., Chabala, J.C., Alberts, A.W. Biochem. Biophys. Res. Commun. (1989) [Pubmed]
  28. Differential regulation of the expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase, synthase, and low density lipoprotein receptor genes. Cuthbert, J.A., Lipsky, P.E. J. Lipid Res. (1992) [Pubmed]
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