Mammalian enzymes of trimethyllysine conversion to trimethylaminobutyrate.

The biosynthesis of carnitine proceeds from trimethyllysine (TML) by beta-hydroxylation by a liver or kidney mitochondrial enzyme, which requires oxygen, alpha-ketoglutarate, ferrous iron, and ascorbate. This dioxygenase is rapidly inactivated by preincubation with Fe2+, but not Fe3+. The evidence suggests that superoxide anion is involved in the hydroxylation. beta-Hydroxytrimethyllysine undergoes aldol cleavage to glycine and trimethylaminobutyraldehyde under the influence of serine hydroxymethyltransferase and possibly a specific aldolase. The next step, the aldehyde oxidation, is catalyzed by a specific NAD-dependent aldehyde dehydrogenase from liver cytosol. The product, trimethylaminobutyrate, is then hydroxylated by a cytosolic dioxygenase to carnitine. This enzyme, which has the same cofactor requirements as TML hydroxylase, is found in the liver of all species examined, but is absent from the kidney of some species.