methylmalonic

Methylmalonic is an adjective used in biochemistry and medicine to refer to methylmalonic acid or to the methylmalonyl group found in certain metabolites and enzymes. In practice, the term appears in the names of compounds such as methylmalonic acid, methylmalonyl-CoA, and enzymes such as methylmalonyl-CoA mutase that act on related substrates.

In human metabolism, methylmalonyl-CoA is produced during the degradation of certain amino acids (valine, isoleucine, methionine, threonine), odd-chain fatty acids, and the side chain of cholesterol. Propionyl-CoA is carboxylated to form D- and L-methylmalonyl-CoA, which are interconverted by epimerase, and finally converted by methylmalonyl-CoA mutase into succinyl-CoA, a TCA cycle intermediate. Methylmalonyl-CoA mutase requires adenosylcobalamin (a form of vitamin B12) as a cofactor.

Clinically, elevated methylmalonic acid in blood or urine is a biomarker for methylmalonic acidemia, a group of inherited metabolic disorders resulting from defects in methylmalonyl-CoA mutase or in the metabolic pathway that provides its cofactor. B12 deficiency can also raise methylmalonic acid levels. Diagnostics rely on biochemical testing and, in many countries, newborn screening programs include methylmalonic acid as a marker. Management focuses on dietary restriction of propionate precursors, treatment with B12 in responsive individuals, and supportive care during metabolic crises.

In biochemistry and organic synthesis, methylmalonyl-derived fragments serve as intermediates in the construction of larger molecules, and the methylmalonyl group can be transformed into malonyl or succinyl units as part of polymer and natural product biosynthesis.

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