Methionine metabolic and trans-selenation pathway enzymes

The methionine metabolic pool and trans-selenation pathway enzymes represent a critical network of proteins responsible for the processing of sulfur- and selenium-containing amino acids. Central to this system is the methionine cycle, which facilitates the production of S-adenosylmethionine (SAM), the universal methyl donor required for the methylation of DNA, RNA, and proteins (Sanderson et al., 2019, Nature Reviews Cancer). The trans-selenation pathway is the selenium-specific analog of the trans-sulfuration pathway, converting selenohomocysteine into selenocysteine, a vital component for the synthesis of antioxidant selenoproteins like glutathione peroxidase (Esaki et al., 1982, Journal of Biological Chemistry). Many malignant cells exhibit 'methionine dependence' (the Hoffman effect), where they are unable to proliferate if exogenous methionine is replaced by homocysteine, making these enzymes attractive targets for cancer therapy (Hoffman, 2019, Cancers). Therapeutic interventions include the use of methioninase to deplete systemic methionine levels and small-molecule inhibitors of methionine adenosyltransferase 2A (MAT2A), which are particularly effective in tumors with methylthioadenosine phosphorylase (MTAP) deletions (Marjon et al., 2016, Cell Reports). Beyond oncology, modulating these enzymes is relevant for treating metabolic disorders like homocystinuria and managing cardiovascular risk associated with elevated homocysteine.

Other names

Methionine cycle enzymesTrans-sulfuration and trans-selenation pathwaySulfur amino acid metabolic enzymesOne-carbon metabolism enzymes

Methionine depletion, Inhibition of S-adenosylmethionine (SAM) synthesis, Reduction of homocysteine levels, Inhibition of cystathionine beta-synthase