Effect of bathocuproine disulfonate, a copper chelator, on cyst(e)ine metabolism by freshly isolated rat hepatocytes.
The metabolism of L-cysteine was studied in freshly isolated rat hepatocytes. Because cysteine is rapidly oxidized in oxygenated incubation medium at neutral pH, the effect of bathocuproine disulfonate, a copper-specific chelator, was investigated. Addition of bathocuproine disulfonate resulted in a higher extracellular cysteine-to-half-cystine ratio in incubations of hepatocytes with cysteine. Bathocuproine disulfonate also increased the total uptake and metabolism of cysteine plus cystine [cyst(e)ine] by hepatocytes, which is consistent with the more efficient transport of cysteine than of cystine by freshly isolated rat hepatocytes. The partitioning of cysteine between cysteinesulfinate-dependent and cysteinesulfinate-independent pathways of catabolism was also altered by the addition of bathocuproine disulfonate; the percentage of total catabolic flux that resulted in taurine plus hypotaurine formation was greater, and the percentage of total catabolic flux that occurred by the beta-cleavage of cystine in a reaction catalyzed by gamma-cystathionase was less in incubations that contained bathocuproine disulfonate. Thus addition of bathocuproine disulfonate to maintain a higher extracellular thiol-to-disulfide ratio favored cysteinesulfinate-dependent catabolism of cysteine in rat hepatocytes.
Coloso
R M
RM
Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853.
Drake
M R
MR
Stipanuk
M H
MH
D000480:Alkynes; D000818:Animals; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology*; D003300:Copper / Q000378:metabolism; D003545:Cysteine / Q000378:metabolism* / Q000494:pharmacology; D003553:Cystine / Q000378:metabolism* / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D010293:Pargyline / Q000031:analogs & derivatives / Q000494:pharmacology; D010618:Phenanthrolines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000480:Alkynes; D002614:Chelating Agents; D010618:Phenanthrolines; D003553:Cystine; C009055:propargylglycine; C028559:bathocuproine sulfonate; D003300:Copper; D010293:Pargyline; D003545:Cysteine; D005998:Glycine