Methionine-oxo-acid transaminase (KYAT1)

Methionine-oxo-acid transaminase is a pyridoxal phosphate-dependent enzyme (EC 2.6.1.88) that catalyzes the reversible transamination of L-methionine to alpha-keto-gamma-methiolbutyrate (KMTB) [2, 7]. In humans, this activity is primarily mediated by Kynurenine aminotransferase 1 (KYAT1), also known as Glutamine transaminase K [8, 10]. This enzyme is a key component of the methionine transamination pathway, which serves as an alternative catabolic route for methionine, particularly when its levels are elevated [8, 19]. The pathway is of significant therapeutic interest because many cancer cells exhibit methionine dependence, a metabolic vulnerability where they require exogenous methionine for survival and proliferation [1, 3, 5, 9]. Beyond oncology, the enzyme has been implicated in the regulation of hepatic glucose metabolism by influencing the acetylation status of PGC-1alpha, making it a potential target for metabolic diseases like type 2 diabetes [8]. Therapeutic strategies currently focus on depleting methionine using recombinant methioninase or inhibiting the transamination step to disrupt cancer cell metabolism [1, 9]. However, challenges remain regarding the potential toxicity of downstream metabolites like methanethiol and the impact on normal methionine-dependent processes [8, 10].

Other names

L-methionine:2-oxo-acid aminotransferaseGlutamine transaminase KKynurenine aminotransferase 1GTKMethionine transaminase

Inhibition of the transamination of L-methionine to alpha-keto-gamma-methiolbutyrate (KMTB), disrupting the methionine transamination pathway and its downstream metabolic and signaling effects.