Cystathionine gamma-lyase (CTH) (CTH)

Cystathionine gamma-lyase (CTH), also known as gamma-cystathionase or CSE, is a vital pyridoxal-5'-phosphate (PLP)-dependent enzyme that catalyzes the final step of the transsulfuration pathway, converting cystathionine into cysteine, ammonia, and alpha-ketobutyrate. Beyond its role in cysteine biosynthesis, CTH is one of the primary enzymes responsible for the production of hydrogen sulfide (H2S) in mammalian cardiovascular and peripheral tissues. H2S acts as a potent gasotransmitter, regulating vascular tone, inflammation, and cellular signaling, which positions CTH as a significant factor in cardiovascular health and blood pressure regulation. [1][2][3] In clinical contexts, genetic deficiency of CTH results in cystathioninuria, a metabolic condition characterized by the accumulation of cystathionine in the blood and urine. CTH has also emerged as a therapeutic target in oncology and inflammatory diseases; its overexpression in certain tumors is linked to enhanced proliferation and chemoresistance, prompting the study of inhibitors like DL-propargylglycine (PAG). Modulating CTH activity offers potential therapeutic avenues for managing hypertension and oxidative stress-related disorders, as the enzyme provides the necessary cysteine for the synthesis of glutathione, the body's major endogenous antioxidant. [1][4][5] Sources: [1] UniProtKB - P32929 (CTH_HUMAN). https://www.uniprot.org/uniprotkb/P32929/entry [2] NCBI Gene ID: 1491, CTH. https://www.ncbi.nlm.nih.gov/gene/1491 [3] Yang G, et al. H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase. Science. 2008. PMID: 18948543. [4] Sun Q, et al. DL-Propargylglycine inhibits H2S production and attenuates inflammation. Br J Pharmacol. 2009. PMID: 19807758. [5] Wang M, et al. Cystathionine gamma-lyase/H2S pathway in cancer: A potential therapeutic target. Pharmacol Res. 2021. PMID: 33454413.

Other names

Gamma-cystathionaseCystathionaseCSECystathionine gamma-homolyase

Inhibition of the enzyme's catalytic activity via competitive or irreversible binding, often targeting the pyridoxal-5'-phosphate (PLP) cofactor, which prevents the conversion of cystathionine to cysteine and reduces the generation of hydrogen sulfide.