Experimental diabetes increases the formation of sulfane by transsulfuration and inactivation of tyrosine aminotransferase in cytosols from rat liver.
The addition of L-cysteine to hepatic cytosols causes inactivation of tyrosine aminotransferase. We have studied the mechanism of inactivation and the effect of streptozotocin-induced diabetes in the rat on the inactivation of tyrosine aminotransferase in the presence of fractions prepared from livers and kidneys. Diabetes increased the rate at which tyrosine aminotransferase was inactivated after addition of cysteine to hepatic cytosols. The inactivation was due to the production of thiocysteine (which contains sulfane sulfur) from cystine as a result of desulfuration catalyzed by gamma-cystathionase. Diabetes increased the content of cystathionine beta-synthase and gamma-cystathionase in liver. As a result, cytosols from diabetic animals converted homocysteine, cystathionine, cysteine and cystine to sulfane at an elevated rate, with resulting inactivation of tyrosine aminotransferase. In contrast, inactivation in kidney fractions was not affected by diabetes. Incubation with an inhibitor of gamma-cystathionase (propargylglycine) prevented inactivation of tyrosine aminotransferase. These results show that the potential for the formation of sulfane sulfur by the enzymes of the transsulfuration pathway is enhanced by chronic diabetes.
Hargrove
J L
JL
Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, GA 30322.
Trotter
J F
JF
Ashline
H C
HC
Krishnamurti
P V
PV
D000818:Animals; D019757:Carbon-Oxygen Lyases; D003545:Cysteine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D003600:Cytosol / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008190:Lyases / Q000378:metabolism; D008297:Male; D051381:Rats; D013379:Substrate Specificity; D014444:Tyrosine Transaminase / Q000037:antagonists & inhibitors*
C060197:thiocysteine; C022696:O-succinylhomoserine (thiol)-lyase; D014444:Tyrosine Transaminase; D008190:Lyases; D019757:Carbon-Oxygen Lyases; D003545:Cysteine