Homocysteinemia: depressed plasma serine levels

Plasma serine levels were found to be lower than normal (mean +/- SD, 91 +/- 18 mumol/L, n = 16) in homocystinuria patients with a deficiency of cystathionine B-synthase on folate therapy, compared with healthy adults (121 +/- 25 mumol/L, n = 25, P less than 0.001). Of 13 other patients with elevated plasma total homocysteine, two patients with homocystinuria due to remethylation defects had normal serine levels, while 11 renal transplant recipients with mild elevations of serum creatinine had lower than normal serine levels (100 +/- 28 mumol/L, P less than .05). Treatment of both the pyridoxine responsive and nonresponsive cystathionine B-synthase-deficient patients with betaine, which lowered plasma homocysteine, also normalized plasma serine levels. In the two patients with remethylating defects however, betaine lowered plasma homocysteine levels without changing plasma serine levels. By contrast, treatment of the renal transplant patients with pyridoxine, folic acid, and vitamin B12 (cofactors required for homocysteine metabolism), caused falls in plasma homocysteine levels, with a concurrent decline in plasma serine levels. These findings may be explained in terms of the requirements for serine in homocysteine metabolism, both as a source of methyl carbon atoms in the methylation of homocysteine by N5-methyltetrahydrofolate and as a substrate in the cystathionine B-synthase reaction. During periods of elevated plasma total homocysteine in man, increased amounts of serine may be diverted to lowering plasma homocysteine.