L-threonine 3-dehydrogenase (TDH)

L-threonine 3-dehydrogenase (TDH) is an enzyme that catalyzes the first step of the threonine catabolic pathway, converting L-threonine and NAD+ into 2-amino-3-ketobutyrate and NADH [Wikipedia; KEGG]. In many organisms, including bacteria and various parasites, this pathway is essential for the production of glycine and acetyl-CoA, which are critical for energy metabolism and cellular growth [Goselle et al., 2025; Cordeiro et al., 2024]. Interestingly, in humans, the TDH gene (located on chromosome 8p23.1) is an expressed pseudogene that does not produce a functional protein due to specific mutations, including the loss of splice sites and the presence of a premature stop codon [Edgar, 2002; NCBI Gene]. Because of its functional absence in humans but essential role in pathogens like Trypanosoma brucei and Trypanosoma cruzi, TDH is considered a highly attractive target for the development of selective anti-parasitic drugs [Edgar, 2002; Goselle et al., 2025]. Inhibitors such as isometamidium chloride and TCMDC-143160 have been shown to disrupt parasite viability by impairing threonine metabolism [Goselle et al., 2025; Cordeiro et al., 2024]. Consequently, targeting this enzyme offers a strategy for treating neglected tropical diseases with potentially minimal off-target effects in human patients [Edgar, 2002]. Furthermore, plasma levels of L-threonine can serve as biomarkers for certain metabolic disorders, highlighting the enzyme's broader relevance in clinical diagnostics [Anal Biochem, 2011].

Other names

L-threonine dehydrogenaseThreonine 3-dehydrogenaseThreonine dehydrogenaseTDHThrDHSDR14E1PTDHP

Inhibition of L-threonine 3-dehydrogenase prevents the conversion of L-threonine to 2-amino-3-ketobutyrate, thereby blocking the primary pathway for glycine and acetyl-CoA production in certain pathogens.