β-하이드록시 β-메틸글루타릴-CoA(영어: β-hydroxy β-methylglutaryl-CoA, HMG-CoA) 또는 3-하이드록시 3-메틸글루타릴-CoA(영어: 3-hydroxy 3-methylglutaryl-CoA)는 메발론산 경로 및 케톤체생성 경로의 대사 중간생성물이다. β-하이드록시 β-메틸글루타릴-CoA(HMG-CoA)는 β-하이드록시 β-메틸글루타릴-CoA 생성효소(HMG-CoA 생성효소)에 의해 아세틸-CoA와 아세토아세틸-CoA로부터 생성된다. 1950년대에 일리노이 대학교 어배너-섐페인의 마이너 제서 쿤(Minor Jesser Coon)과 비말 쿠마르 바크하와트(Bimal Kumar Bachhawat)의 연구가 이러한 발견을 이끌었다.[1][2]
β-하이드록시 β-메틸글루타릴-CoA(HMG-CoA)는 류신, 아이소류신, 발린과 같은 가지사슬 아미노산의 대사 과정에서의 대사 중간생성물이다.[3] β-메틸글루타코닐-CoA(MG-CoA)와 β-하이드록시 β-메틸뷰티릴-CoA(HMB-CoA)는 β-하이드록시 β-메틸글루타릴-CoA(HMG-CoA)의 직접적인 전구물질들이다.
메발론산의 합성은 두 분자의 아세틸-CoA가 싸이올레이스에 의해 클라이젠 축합되어 아세토아세틸-CoA를 생성하는 것으로 시작된다. 다음 반응은 아세틸-CoA와 아세토아세틸-CoA가 β-하이드록시 β-메틸글루타릴-CoA 생성효소(HMG-CoA 생성효소)에 의해 β-하이드록시 β-메틸글루타릴-CoA(HMG-CoA)를 생성하는 반응이다.[7]
↑Zanchi NE, Gerlinger-Romero F, Guimarães-Ferreira L, de Siqueira Filho MA, Felitti V, Lira FS, Seelaender M, Lancha AH (April 2011). “HMB supplementation: clinical and athletic performance-related effects and mechanisms of action”. 《Amino Acids》 40 (4): 1015–1025. doi:10.1007/s00726-010-0678-0. PMID20607321. HMB is a metabolite of the amino acid leucine (Van Koverin and Nissen 1992), an essential amino acid. The first step in HMB metabolism is the reversible transamination of leucine to [α-KIC] that occurs mainly extrahepatically (Block and Buse 1990). Following this enzymatic reaction, [α-KIC] may follow one of two pathways. In the first, HMB is produced from [α-KIC] by the cytosolic enzyme KIC dioxygenase (Sabourin and Bieber 1983). The cytosolic dioxygenase has been characterized extensively and differs from the mitochondrial form in that the dioxygenase enzyme is a cytosolic enzyme, whereas the dehydrogenase enzyme is found exclusively in the mitochondrion (Sabourin and Bieber 1981, 1983). Importantly, this route of HMB formation is direct and completely dependent of liver KIC dioxygenase. Following this pathway, HMB in the cytosol is first converted to cytosolic β-hydroxy-β-methylglutaryl-CoA (HMG-CoA), which can then be directed for cholesterol synthesis (Rudney 1957) (Fig. 1). In fact, numerous biochemical studies have shown that HMB is a precursor of cholesterol (Zabin and Bloch 1951; Nissen et al. 2000).
↑Kohlmeier M (May 2015). 〈Leucine〉. 《Nutrient Metabolism: Structures, Functions, and Genes》 2판. Academic Press. 385–388쪽. ISBN978-0-12-387784-0. 2016년 6월 6일에 확인함. Energy fuel: Eventually, most Leu is broken down, providing about 6.0kcal/g. About 60% of ingested Leu is oxidized within a few hours ... Ketogenesis: A significant proportion (40% of an ingested dose) is converted into acetyl-CoA and thereby contributes to the synthesis of ketones, steroids, fatty acids, and other compounds Figure 8.57: Metabolism of L-leucine
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