Date of Award
Doctor of Philosophy
John T. Smith
Jane R. Savage, Robert H. Feinberg, Frances A. Schofield
Since previous results in this laboratory had indicated that vitamin E was necessary in vivo not only for the optimal sulfation of mucopolysaccharides, but also for the oxidation of neutral sulfur to sulfate, the ability of whole liver homogenates from vitamin Esufficient and -deficient rats to convert cysteine to sulfate was investigated. Then an attempt was made to determine the specific site of the decreased oxidation of cysteine or its intermediate oxidation products. Since several alternative pathways have been proposed in animals for the ultimate oxidation of the sulfur of cysteine to sulfate and the use of the sulfate formed, it was necessary to limit this investigation to the most widely accepted pathway, that of the oxidation of cysteine to sulfate through cysteinesulfinic acid and sulfite. Low sulfate diets were employed to force the animals to satisfy their inorganic sulfate needs by the oxidation of the sulfur amino acids.
A statistically significant decrease in the conversion of 35S-cysteine to 35S-sulfate was found in whole liver homogenates from the vitamin E-deficient male, but not the female, rats fed the low sulfate diets when these were compared to their littermate controls. When male and female rats fed normal sulfate vitamin E-sufficients diets were compared, there was no statistically significant difference in the conversion of 35S -cysteine to 35S-sulfate. There was a statistically significant decrease in the ability of mitochondrial homogenates from 35 the vitamin E-deficient "prepped" female rats to convert 35S-cysteine to 35S-sulfate when these were compared with their littermate controls. No difference could be detected in the ability of acetone powder extracts from vitamin E-deficient and -sufficient male rats to oxidize sulfite to sulfate, as indicated by ferricyanide reduction. Tests were made to determine the presence of cysteinesulfinic acid and sulfite after incubation of cysteine with denucleated homogenates, but neither substance could be detected. The conversion of cysteine to a ninhydrinpositive material thought to be cysteinesulfinic acid by supernatant preparations of liver from vitamin E-deficient and -sufficient male and female rats was also studied in the presence of an inhibitor. There was no detectable difference in the ability of these preparations to oxidize cysteine.
A mechanism is proposed for the involvement of ATP in the oxidation of the sulfur group of cysteine to sulfate, since ATP, as well as vitamin E, is implicated in this conversion by results found during the course of this research.
Rutledge, Helen Raisty, "Inhibition of Cysteine Oxidation in Vitamin E Deficiency. " PhD diss., University of Tennessee, 1967.