3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial) is an enzyme in humans that is encoded by the HMGCS2 gene.[5]
The protein encoded by this gene belongs to the HMG-CoA synthase family. It is a mitochondrial enzyme that catalyzes the second and rate-limiting reaction of ketogenesis, a metabolic pathway that provides lipid-derived energy for various organs during times of carbohydrate deprivation, such as fasting, by addition of a third acetyl group to acetoacetyl-CoA, producing HMG-CoA.[6]
Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[5]
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土曜教室-第3回-ケトン体-29-結論
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Clinical significance
Mutations in this gene are associated with mitochondrial HMG-CoA synthase deficiency (also known as HMGCS2D), affecting ketone body synthesis.[7] Affected patients are unable to perform ketogenesis during starvation and times of higher energy need such as fever and vigorous exercise. Commonly found is damage to heart muscles and the brain, along with hypoglycemia (not always present)[8] and elevated blood fatty acid concentration. The mortality rate is 20%.[9] Urine organic acid analysis can be used to detect likely cases, which can be further confirmed using DNA sequencing.[10]
Occurrence
HMGCS2 is not found in cetaceans, elephantids, or Old World fruit bats. Fruit bats are known to be very sensitive to starvation, similar to humans with HMGCS2D. The other two groups seem to have evolved other means of coping with starvation.[11]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000134240 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027875 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b "Entrez Gene: 3-hydroxy-3-methylglutaryl-CoA synthase 2 (mitochondrial)".
- ^ Drabbe S, Pelzer A, Slenter D, Willighagen E (February 2023). "Disorders in ketone body synthesis (Homo sapiens)". Wiki Pathways.
- ^ Aledo R, Mir C, Dalton RN, Turner C, Pié J, Hegardt FG, et al. (February 2006). "Refining the diagnosis of mitochondrial HMG-CoA synthase deficiency". Journal of Inherited Metabolic Disease. 29 (1): 207–211. doi:10.1007/s10545-006-0214-2. PMID 16601895. S2CID 24866271.
- ^ Conlon, TA; Fitzsimons, PE; Borovickova, I; Kirby, F; Murphy, S; Knerr, I; Crushell, E (September 2020). "Hypoglycemia is not a defining feature of metabolic crisis in mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: Further evidence of specific biochemical markers which may aid diagnosis". JIMD Reports. 55 (1): 26–31. doi:10.1002/jmd2.12146. PMC 7463059. PMID 32905056.
- ^ 丹, 马; 丹, 俞 (11 November 2018). "线粒体3-羟基3-甲基戊二酰辅酶A合成酶缺乏症1例并文献复习" [Mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase deficiency: a case report and literature review]. Chinese Journal of Contemporary Pediatrics (in Chinese). 20 (11): 930–933. doi:10.7499/j.issn.1008-8830.2018.11.010. ISSN 1008-8830. PMC 7389032. PMID 30477625.
- ^ Conlon, TA; Fitzsimons, PE; Borovickova, I; Kirby, F; Murphy, S; Knerr, I; Crushell, E (September 2020). "Hypoglycemia is not a defining feature of metabolic crisis in mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: Further evidence of specific biochemical markers which may aid diagnosis". JIMD Reports. 55 (1): 26–31. doi:10.1002/jmd2.12146. PMC 7463059. PMID 32905056.
- ^ Jebb D, Hiller M (October 2018). "Recurrent loss of HMGCS2 shows that ketogenesis is not essential for the evolution of large mammalian brains". eLife. 7: e38906. doi:10.7554/eLife.38906. PMC 6191284. PMID 30322448.
External links
- Overview of all the structural information available in the PDB for UniProt: P54868 (Human Hydroxymethylglutaryl-CoA synthase, mitochondrial) at the PDBe-KB.
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This page was last edited on 29 November 2023, at 03:33