Vitamin B-6 deficiency in rats reduces hepatic serine hydroxymethyltransferase and cystathionine beta-synthase activities and rates of in vivo protein turnover, homocysteine remethylation and transsulfuration

Vitamin B-6 deficiency causes mild elevation in plasma homocysteine, but th e mechanism has not been clearly established. Serine is a substrate in one- carbon metabolism and in the transsulfuration pathway of homocysteine catab olism, and pyridoxal phosphate (PLP) plays a key role as coenzyme for serin e hydroxymethyltransferase (SHMT) and enzymes of transsulfuration. In this study we used [H-2(3)]serine as a primary tracer to examine the remethylati on pathway in adequately nourished and vitamin B-6-deficient rats pi and 0. 1 mg pyridoxine (PN)/kg diet]. [H-2(3)]Leucine and [1-C-13]methionine were also used to examine turnover of protein and methionine pools, respectively , All tracers were injected intraperitoneally as a bolus dose, and then rat s 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 concentrat ions, reduced liver SHMT activity, greater plasma and liver total homocyste ine concentration, and reduced liver S-adenosylmethionine concentration. He patic and whole body protein turnover were reduced in vitamin B-6-deficient rats as evidenced by greater isotopic enrichment of [H-2(3)]leucine. Hepat ic [H-2(2)]methionine production from [H-2(3)]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-beta-synt hase activity, and in vivo hepatic transsulfuration flux shown by productio n of [H-2(3)]cysteine from the [H-2(3)]serine increased over twofold. In co ntrast, plasma appearance of [H-2(3)]cysteine was decreased by 89% in vitam in B-6 deficiency. The rate of hepatic homocysteine production shown by the ratio of [1-C-13]homocysteine/[1-C-13]methionine areas under enrichment vs . time curves was not affected by vitamin B-6 deficiency. Overall, these re sults indicate that vitamin B-6 deficiency substantially affects one-carbon metabolism by impairing both methyl group production for homocysteine reme thylation and flux through whole-body transsulfuration.