Abstract
The oxidation of cysteine in mammalian cells occurs by two routes: a highly regulated direct oxidation pathway in which the first step is catalyzed by cysteine dioxygenase (CDO) and by desulfhydration-oxidation pathways in which the sulfur is released in a reduced oxidation state. To assess the effect of a lack of CDO on production of hydrogen sulfide (H2S) and thiosulfate (an intermediate in the oxidation of H2S to sulfate) and to explore the roles of both cystathionine γ-lyase (CTH) and cystathionine β-synthase (CBS) in cysteine desulfhydration by liver, we investigated the metabolism of cysteine in hepatocytes isolated from Cdo1-null and wild-type mice. Hepatocytes from Cdo1-null mice produced more H2S and thiosulfate than did hepatocytes from wild-type mice. The greater flux of cysteine through the cysteine desulfhydration reactions catalyzed by CTH and CBS in hepatocytes from Cdo1-null mice appeared to be the consequence of their higher cysteine levels, which were due to the lack of CDO and hence lack of catabolism of cysteine by the cysteinesulfinate-dependent pathways. Both CBS and CTH appeared to contribute substantially to cysteine desulfhydration, with estimates of 56 % by CBS and 44 % by CTH in hepatocytes from wild-type mice, and 63 % by CBS and 37 % by CTH in hepatocytes from Cdo1-null mice.
Original language | English |
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Pages (from-to) | 1353-1365 |
Number of pages | 13 |
Journal | Amino Acids |
Volume | 46 |
Issue number | 5 |
DOIs | |
Publication status | Published - 2014 May |
Externally published | Yes |
Keywords
- Cystathionine β-synthase
- Cystathionine γ-lyase
- Cysteine
- Cysteine dioxygenase
- Hepatocytes
- Hydrogen sulfide
- Mice
- Thiosulfate
ASJC Scopus subject areas
- Biochemistry
- Organic Chemistry
- Clinical Biochemistry