ロイシンからHMBへの代謝経路[5]
English: This image is a screenshot of en:Template:Leucine metabolism in humans; it is intended for external (i.e., off-wiki) use. This illustration depicts the primary metabolic pathways of L-leucine in humans which involve β-hydroxy β-methylbutyrate and isovaleryl-CoA as metabolites.[1][2][3][4][5] A third human metabolic pathway – which accounts for a very small fraction of leucine metabolism and involves the conversion of L-leucine into β-leucine by leucine aminomutase[3] – is not depicted in this image. Of the two major pathways, L-leucine is mostly metabolized into isovaleryl-CoA, while only about 5% is metabolized into HMB.[1][2][3] References for the diagram and description: ↑ a b  (February 2013). "International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB)". Journal of the International Society of Sports Nutrition 10 (1): 6. DOI:10.1186/1550-2783-10-6. PMID 23374455. PMC: 3568064. ↑ a b  (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. PMID 20607321. "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). In the second pathway, after transamination, [α-KIC] in liver generates isovaleryl-CoA through the enzymatic action of branched-chain ketoacid dehydrogenase (BCKD) and after several steps, there is production of HMG-CoA through the enzyme HMG-CoA synthase (Fig. 1). Under normal conditions the majority of KIC is converted into isovaleryl-CoA, in which approximately 5% of leucine is metabolized into HMB (Wilson et al. 2008; Van Koverin and Nissen 1992). However, Nissen and Abumrad (1997) provided evidence that the primary fate of HMB is probably conversion to HMG-CoA in the liver, for cholesterol biosynthesis." ↑ a b c (May 2015) Nutrient Metabolism: Structures, Functions, and Genes (2nd ed.), Academic Press, pp. 385–388 Retrieved on 6 June 2016. ISBN: 9780123877840.  “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 ↑ KEGG Reaction: R10759. Kyoto Encyclopedia of Genes and Genomes. Kanehisa Laboratories. Retrieved on 24 June 2016. ↑  (November 2011). "Urinary excretion of 3-hydroxyisovaleric acid and 3-hydroxyisovaleryl carnitine increases in response to a leucine challenge in marginally biotin-deficient humans". The Journal of Nutrition 141 (11): 1925–1930. DOI:10.3945/jn.111.146126. PMID 21918059. PMC: 3192457. "Metabolic impairment diverts methylcrotonyl CoA to 3-hydroxyisovaleryl CoA in a reaction catalyzed by enoyl-CoA hydratase (22, 23). 3-Hydroxyisovaleryl CoA accumulation can inhibit cellular respiration either directly or via effects on the ratios of acyl CoA:free CoA if further metabolism and detoxification of 3-hydroxyisovaleryl CoA does not occur (22). The transfer to carnitine by 4 carnitine acyl-CoA transferases distributed in subcellular compartments likely serves as an important reservoir for acyl moieties (39–41). 3-Hydroxyisovaleryl CoA is likely detoxified by carnitine acetyltransferase producing 3HIA-carnitine, which is transported across the inner mitochondrial membrane (and hence effectively out of the mitochondria) via carnitine-acylcarnitine translocase (39). 3HIA-carnitine is thought to be either directly deacylated by a hydrolase to 3HIA or to undergo a second CoA exchange to again form 3-hydroxyisovaleryl CoA followed by release of 3HIA and free CoA by a thioesterase."