2-amino-3-ketobutyrate coenzyme A ligase (KBL)

2-amino-3-ketobutyrate coenzyme A ligase (KBL), also known as glycine C-acetyltransferase (GCAT), is a mitochondrial enzyme that catalyzes the second step of the threonine degradation pathway [1, 10]. It is a pyridoxal phosphate (PLP)-dependent enzyme that facilitates the cleavage of 2-amino-3-ketobutyrate into glycine and acetyl-CoA [11, 13]. Although the first enzyme in this pathway, threonine dehydrogenase, is a pseudogene in humans, GCAT remains functional and plays a significant role in glycine homeostasis, one-carbon metabolism, and the regulation of mitochondrial translation [19, 20]. In therapeutic contexts, GCAT is considered a potential target for treating parasitic infections like Chagas disease, as Trypanosoma cruzi relies on this pathway for energy production [6, 28]. Furthermore, GCAT has been implicated in cancer biology, specifically in chronic myeloid leukemia (CML) stem cells, where its activity prevents the toxic accumulation of methylglyoxal [19]. Inhibition of GCAT or its regulatory network is being explored as a strategy to selectively eliminate cancer stem cells or disrupt parasite metabolism [6, 19]. While no FDA-approved drugs specifically target GCAT, research continues into small molecule inhibitors and the enzyme's role as a biomarker for metabolic and oncological conditions [19, 26].

Other names

Glycine C-acetyltransferaseAKB ligaseAminoacetone synthase2-amino-3-ketobutyrate-CoA ligaseGCAT

Inhibition of the enzymatic cleavage of 2-amino-3-ketobutyrate into glycine and acetyl-CoA, thereby disrupting amino acid catabolism, glycine homeostasis, and mitochondrial protein synthesis.