Cysteine Metabolism

This refers to the biological pathways that consume or create cysteine. In humans cysteine catabolism is tightly regulated via regulation of cysteine dioxygenase (CDO) levels in the liver, with the turnover of CDO protein being dramatically decreased when intracellular cysteine levels increase. This occurs in response to changes in the intracellular cysteine concentration via changes in the rate of CDO ubiquitination and degradation. Expressed at high levels in the liver with lower levels in the kidney, brain, and lung, cysteine dioxygenase catalyzes the addition of molecular oxygen to the sulfhydryl group of cysteine, yielding cysteinesulfinic acid (also known as 3-sulfinoalanine). The oxidative catabolism of cysteine to cysteinesulfinate by CDO represents an irreversible loss of cysteine from the free amino acid pool. Once generated, cysteinesulfinate is shuttled into several pathways including hypotaurine/taurine synthesis, sulfite/sulfate production, and the generation of pyruvate. Another route to controlling cysteine levels is through glutathione synthesis. Glutathione synthesis increases when intracellular cysteine levels increase as a result of increased saturation of glutamate-cysteine ligase (GCL) with cysteine, and this contributes to removal of excess cysteine. In addition, to these routes for cysteine consumption or loss, several other enzymes contribute to cysteine catabolism: cysteine lyase will generate L-cysteate, cystine reductase will reversibly generate L-cystine and cysteine transaminase will generate 3-mercaptopyruvate while amino acid racemase will convert L-cysteine to D-cysteine. Cysteine is also consumed through pantothenate/CoA biosynthesis. In pantothenate/CoA biosynthesis the first step in the pathway is catalyzed by pantothenate kinase. Cysteine is condensed with pantothenate in the second step of the coenzyme A synthesis pathway to form 4’-phosphopantothenoylcysteine, and the cysteine moiety is decarboxylated in the third step of the pathway to form the cysteamine moiety of coenzyme A. While diet is one of the main sources of cysteine, this amino acid can also be synthesized from O-acetyl-L-serine via cysteine synthase. It is also synthesized via pyruvate (via cystathionine gamma-lyase) or 3-mecrapto-pyruvate (via cysteine transaminase). L-cysteine is also a product of glycine, serine, and threonine metabolism.

References

1. Lehninger, A.L. (2005) Lehninger principles of biochemistry (4 ^th ed.). New York: W.H Freeman.
2. Salway, J.G. (2004) Metabolism at a glance (3 ^rd ed.). Alden, Mass. : Blackwell Pub.