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The Cysteine dioxygenase knockout mouse: altered cysteine metabolism leading to excess hydrogen sulfide production
Author(s) -
Stipanuk Martha H,
Roman Heather B.,
Hirschberger Lawrence L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.113.5
Subject(s) - hypotaurine , taurine , cysteine , chemistry , cysteine metabolism , biochemistry , cystathionine gamma lyase , cystathionine beta synthase , aminooxyacetic acid , metabolism , kidney , hydrogen sulfide , endocrinology , amino acid , enzyme , biology , sulfur , organic chemistry
Cysteine dioxygenase (CDO) catalyzes the first step in the oxidative metabolism of cysteine and is strongly regulated in response to dietary sulfur amino acid intake. To define the consequences of loss of CDO on cysteine metabolism at the tissue level, we determined levels of relevant metabolites and enzymes and evidence of H 2 S toxicity in liver, pancreas, kidney and lung of CDO −/− mice fed either a taurine‐free or taurine‐supplemented diet. CDO −/− mice had low tissue and serum taurine and hypotaurine levels and high tissue levels of cysteine, consistent with loss of CDO. CDO −/− mice had elevated urinary excretion of thiosulfate, high tissue and serum cystathionine and lanthionine levels, and evidence of inhibition and destabilization of cytochrome c oxidase, consistent with excess production of H 2 S. The CDO −/− mouse clearly demonstrates that H 2 S production in tissues can exceed the capacity of the animal to oxidize sulfide to sulfate and demonstrates that pancreas and lung are more susceptible to toxicity from endogenous H 2 S production than are liver and kidney. Supported by NIH Grant DK‐056649.