The enzyme belongs to the family of transferases, specifically those acyltransferases that convert acyl groups into alkyl groups on transfer. The systematic name of this enzyme class is acetyl-CoA:3-methyl-2-oxobutanoate C-acetyltransferase (thioester-hydrolysing, carboxymethyl-forming). Other names in common use include 3-carboxy-3-hydroxy-4-methylpentanoate 3-methyl-2-oxobutanoate-lyase, (CoA-acetylating), alpha-isopropylmalate synthetase, alpha-isopropylmalate synthase, alpha-isopropylmalic synthetase, isopropylmalate synthase, and isopropylmalate synthetase. This enzyme participates in biosynthesis of L-leucine and pyruvate metabolism. Monovalent and divalent cation activation have been reported for enzymes from different sources.
Mycobacterium tuberculosis α-isopropylmalate synthase requires a divalent metal ion, of which Mg2+ and Mn2+ give highest activity, and a monovalent cation, with K+ as the best activator. Zn2+ was shown to be an inhibitor, contrary to what was assumed from the structural data. In addition to the complex requirements for a divalent metal and further activation by K+, M. tuberculosis α-isopropylmalate synthase follows a random kinetic mechanism for catalysis. Another feature of the M. tuberculosis homolog is that L-leucine, the feedback inhibitor, inhibits the enzyme in a time-dependent fashion. This was the first demonstration of a feedback inhibitor that displays slow-onset inhibition.
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^Kohlhaw G, Leary TR, Umbarger HE (1969). "Alpha-isopropylmalate synthase from Salmonella typhimurium Purification and properties". J. Biol. Chem. 244 (8): 2218–25. PMID4976555.
^Webster RE; Gross, SR (1965). "The alpha-isopropylmalate synthetase of Neurospora. I. The kinetics and end product control of alpha-isopropylmalate synthetase function". Biochemistry. 4 (11): 2309–2327. doi:10.1021/bi00887a008.
^Carvalho LP, Blanchard, JS (2006). "Kinetic analysis of the effects of monovalent cations and divalent metals on the activity of Mycobacterium tuberculosis alpha-isopropylmalate synthase". Archives of Biochemistry and Biophysics. 451 (2): 141–48. PMID16684501. doi:10.1016/j.abb.2006.03.030.
^Carvalho LP, Argyrou A, Blanchard, JS (2005). "Slow-onset Feedback Inhibition: Inhibition of Mycobacterium tuberculosis alpha-Isopropylmalate Synthase by L-Leucine". Journal of the American Chemical Society. 127 (28): 10004–5. PMID16011356. doi:10.1021/ja052513h.