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

  • Homocysteine and B-Vitamin Metabolism
  • Published:
Journal of Inherited Metabolic Disease

Abstract

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.

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Abbreviations

Met:

L-methionine

Cys:

L-cysteine

Hcy:

L-homocysteine

SAA:

Sulfur-containing amino acids

CBS:

Cystathionine β-synthase

CSE:

Cystathionine γ-lyase

CDO:

Cysteine dioxygenase

CSD:

Cysteinesulfinate decarboxylase

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Acknowledgement

This work was supported in part by grant DK056649 from the National Institute of Diabetes and Digestive and Kidney Diseases. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH

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  1. Division of Nutritional Sciences, Cornell University, Ithaca, NY, 14853, USA

    Martha H. Stipanuk & Iori Ueki

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  1. Martha H. Stipanuk
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Correspondence to Martha H. Stipanuk.

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Communicated editor: Viktor Kozich

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Stipanuk, M.H., Ueki, I. Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur. J Inherit Metab Dis 34, 17–32 (2011). https://doi.org/10.1007/s10545-009-9006-9

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  • DOI: https://doi.org/10.1007/s10545-009-9006-9

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