title: Primary hepatocytes from mice lacking cysteine dioxygenase show increased cysteine concentrations and higher rates of metabolism of cysteine to hydrogen sulfide and thiosulfate.
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.
authors.affiliation: Division of Nutritional Sciences, Cornell University, 227 Savage Hall, Ithaca, NY, 14853, USA.
authors.forename: Halina
authors.initials: H
authors.lastname: Jurkowska
authors.forename: Heather B
authors.initials: HB
authors.lastname: Roman
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Hirschberger
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sasakura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nagano
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Hanaoka
authors.forename: Jakub
authors.initials: J
authors.lastname: Krijt
authors.forename: Martha H
authors.initials: MH
authors.lastname: Stipanuk
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D050558:Cysteine Dioxygenase / Q000172:deficiency / Q000235:genetics*; D005260:Female; D022781:Hepatocytes / Q000201:enzymology / Q000378:metabolism*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013885:Thiosulfates / Q000378:metabolism*
chemical_list: D013885:Thiosulfates; D050558:Cysteine Dioxygenase; D003545:Cysteine; D006862:Hydrogen Sulfide