Figure 4. TDH-Mediated Catabolism of Threonine.

Threonine is catabolized to acetyl-CoA and glycine via a two-step process, first involving the rate-limiting threonine dehydrogenase (TDH) enzyme yielding the short-lived intermediate 2-amino-3-ketobutyrate. This intermediate is subsequently subject to the 2-amino-3-ketobutyrate ligase (KBL) enzyme that, supplemented by coenzyme A (CoA), yields the final products of the reaction, acetyl-CoA and glycine. Both steps of the catabolic reaction take place in the mitochondria of eukaryotic cells. The former product, acetyl-CoA,can be fed into the TCA cycle or used as an anabolic building block for other metabolites. The latter product, glycine, is used to feed the mitochondrial glycine cleavage system for the conversion of tetrahydrofolate (THF) into N⁵, N¹⁰-methylene-tetrahydrofolate (MTHF). MTHF, in turn, is capable of one-carbon donation in biosynthetic reactions involving purine and pyrimidine synthesis, as well as the regeneration of methionine from homocysteine.