Graduate Thesis Or Dissertation
 

Vitamin B-6 and pyrimidine deoxynucleoside metabolism in the rat

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  • Serine transhydroxymethylase (STHM), a pyridoxal 5'- phosphate requiring enzyme is indirectly involved in pyrimidine deoxynucleotide metabolism. A decrease in the activity of this enzyme could lead to altered deoxycytidine (dC) metabolism. This study was undertaken to determine if a vitamin B-6 deficiency affects dC metabolism. The effect of a vitamin B-6 deficiency on the activity of STHM in liver, thymus, spleen and bone marrow was examined. In addition, the effect of a vitamin B-6 deficiency on urinary excretion of dC was examined. The effect of a vitamin B-6 deficiency on the urinary excretion and tissue retention of ³H label from ip injected ³H-dC was monitored. Rats were assigned in groups of six to one of four treatment groups: ad libitum control (ALC), pair fed control (PFC), ad libitum deficient (ALD) or meal fed deficient (MFD). At the end of weeks 2 and 6, rats from each treatment group received an ip injection of ³H-dC. Urines were collected for 24 hours following the ip inhibited due to lack of cofactor, then dTMP levels would fall. In an attempt to increase the concentration of dTMP, enzymes active in the conversion of dC and dCMP to dUMP would be expected to increase. Thus, dC salvage pathways would increase and dC synthesis would decrease as metabolism shifts toward production of deoxythymidine triphosphate (dTTP). The result would be lower urinary dC excretion. The present study was undertaken to explore the relationship between vitamin B-6 and pyrimidine deoxynucleotide metabolism. There were four hypothesis tested: Vitamin B-6 deficient rats will excrete less urinary dC than either ad libitum or pair fed controls; vitamin B-6 deficient rats will excrete a lower percentage of labeled dC in urine than control rats; vitamin B-6 deficient rats will incorporate less labeled dC into DNA than control rats but may retain more label in tissues as dC metabolites; activity of STHM from tissues of vitamin B-6 deficient rats will be lower than that from the control rats.
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