Cystathionine β-Synthase in Physiology and Cancer

Figure 1

Metabolic reactions catalyzed by CBS. CBS catalyzes the condensation of homocysteine (Hcy) with serine to form cystathionine which is subsequently cleaved by cystathionine gamma-lyase (CTH) to form cysteine, a precursor of glutathione. CBS also catalyzes the production of H₂S. In addition to CBS, CTH and 3-mercaptopyruvate sulfurtransferase (3-MST) are also involved in the conversion of cysteine to H₂S. Homocysteine is another key CBS-derived metabolite and is linked to the metabolism of methionine. Methionine is converted to homocysteine via S-adenosyl methionine (SAM) and S-adenosyl homocysteine (SAH), releasing a methyl group that is used in numerous methylation reactions. SAM is an allosteric activator of CBS. 3-MST, 3-mercaptopyruvate sulfurtransferase; AHCY, adenosylhomocysteinase; BHMT, betaine-homocysteine methyltransferase; CAT, cysteine aminotransferase; CBS, cystathionine β-synthase; CTH, cystathionine gamma-lyase; GCLC, gamma-glutamylcysteine synthetase; GSS, glutathione synthetase; MAT1A/2A, methionine adenosyltransferase 1A/2A; MTHFR, methylenetetrahydrofolate reductase; MTR, 5-methyltetrahydrofolate-homocysteine methyltransferase; SAM, S-adenosyl methionine; SAH, S-adenosyl homocysteine; SHMT, serine hydroxymethyltransferase.