Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur

• Published in: Journal of inherited metabolic disease Vol. 34; no. 1; pp. 17 - 32
• Main Authors: Stipanuk, Martha H, Ueki, Iori
• Format: Journal Article
• Language: English
• Published: Dordrecht Dordrecht : Springer Netherlands 01.02.2011; Springer Netherlands; Blackwell Publishing Ltd
• Subjects: Amino acids; Animals; Biochemistry; Cystathionine beta -synthase; Cystathionine gamma -lyase; Cysteine; Cysteine - metabolism; Cysteine dioxygenase; Diets; homocysteine; Homocysteine - metabolism; Homocysteine and B-Vitamin Metabolism; Human Genetics; Humans; Hydrogen sulfide; Internal Medicine; Low protein diet; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolic Networks and Pathways; Metabolism; Metabolites; Methionine; Methionine - metabolism; Methylenetetrahydrofolate reductase; Models, Biological; Oxidation; Pediatrics; Rats; S-Adenosylmethionine; Sulfate; Sulfur; Sulfur - metabolism; Sulfur Compounds - metabolism; Taurine; Taurine - metabolism; Thiols; Transsulfuration Pathway; Taurine; Sulfite Oxidase; Hypotaurine; Cystathionine
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-009-9006-9

Synthesis of cysteine as a product of the transsulfuration pathway can be viewed as part of methionine or homocysteine degradation, with cysteine being the vehicle for sulfur conversion to end products (sulfate, taurine) that can be excreted in the urine. Transsulfuration is regulated by stimulation of cystathionine β-synthase and inhibition of methylene tetrahydrofolate reductase in response to changes in the level of S-adenosylmethionine, and this promotes homocysteine degradation when methionine availability is high. Cysteine is catabolized by several desulfuration reactions that release sulfur in a reduced oxidation state, generating sulfane sulfur or hydrogen sulfide (H₂S), which can be further oxidized to sulfate. Cysteine desulfuration is accomplished by alternate reactions catalyzed by cystathionine β-synthase and cystathionine γ-lyase. Cysteine is also catabolized by pathways that require the initial oxidation of the cysteine thiol by cysteine dioxygenase to form cysteinesulfinate. The oxidative pathway leads to production of taurine and sulfate in a ratio of approximately 2:1. Relative metabolism of cysteine by desulfuration versus oxidative pathways is influenced by cysteine dioxygenase activity, which is low in animals fed low-protein diets and high in animals fed excess sulfur amino acids. Thus, desulfuration reactions dominate when cysteine is deficient, whereas oxidative catabolism dominates when cysteine is in excess. In rats consuming a diet with an adequate level of sulfur amino acids, about two thirds of cysteine catabolism occurs by oxidative pathways and one third by desulfuration pathways. Cysteine dioxygenase is robustly regulated in response to cysteine availability and may function to provide a pathway to siphon cysteine to less toxic metabolites than those produced by cysteine desulfuration reactions.