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Article

Vitamin B-6 Deficiency in Rats Reduces Hepatic Serine Hydroxymethyltransferase and Cystathionine ß-Synthase Activities and Rates of In Vivo Protein Turnover, Homocysteine Remethylation and Transsulfuration^{1 ,2}

Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611-0370

³To whom correspondence should be addressed.

Vitamin B-6 deficiency causes mild elevation in plasma homocysteine, but the mechanism has not been clearly established. Serine is a substrate in one-carbon metabolism and in the transsulfuration pathway of homocysteine catabolism, and pyridoxal phosphate (PLP) plays a key role as coenzyme for serine hydroxymethyltransferase (SHMT) and enzymes of transsulfuration. In this study we used [²H₃]serine as a primary tracer to examine the remethylation pathway in adequately nourished and vitamin B-6-deficient rats [7 and 0.1 mg pyridoxine (PN)/kg diet]. [²H₃]Leucine and [1-¹³C]methionine were also used to examine turnover of protein and methionine pools, respectively. All tracers were injected intraperitoneally as a bolus dose, and then rats were killed (n = 4/time point) after 30, 60 and 120 min. Rats fed the low-PN diet had significantly lower growth and plasma and liver PLP concentrations, reduced liver SHMT activity, greater plasma and liver total homocysteine concentration, and reduced liver S-adenosylmethionine concentration. Hepatic and whole body protein turnover were reduced in vitamin B-6-deficient rats as evidenced by greater isotopic enrichment of [²H₃]leucine. Hepatic [²H₂]methionine production from [²H₃]serine via cytosolic SHMT and the remethylation pathway was reduced by 80.6% in vitamin B-6 deficiency. The deficiency did not significantly reduce hepatic cystathionine-ß-synthase activity, and in vivo hepatic transsulfuration flux shown by production of [²H₃]cysteine from the [²H₃]serine increased over twofold. In contrast, plasma appearance of [²H₃]cysteine was decreased by 89% in vitamin B-6 deficiency. The rate of hepatic homocysteine production shown by the ratio of [1-¹³C]homocysteine/[1-¹³C]methionine areas under enrichment vs. time curves was not affected by vitamin B-6 deficiency. Overall, these results indicate that vitamin B-6 deficiency substantially affects one-carbon metabolism by impairing both methyl group production for homocysteine remethylation and flux through whole-body transsulfuration.

KEY WORDS: • one-carbon metabolism • homocysteine • transsulfuration • vitamin B-6 • rats

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