Accumulation of Homocyst(e)ine in Vitamin B-6 Deficiency: a Model for the Study of Cystathionine β-Synthase Deficiency

Abstract

The accumulation of homocyst(e)ine in rats deficient in vitamin B-6 was monitored. Homocysteine and cysteine linked by disulfide bonds to plasma proteins, to red blood cell (RBC) membranes, and free in plasma were analyzed by HPLC separation and electrochemical detection. As the vitamin B-6 deficiency progressed, the concentration of plasma protein-bound and RBC membrane-bound homocysteine increased and that of cysteine decreased. Changes in free homocysteine concentration paralleled those seen in protein-bound homocysteine, but free cysteine concentration did not fluctuate throughout the deficiency. Refeeding vitamin B-6 to deficient animals resulted in a return of homocysteine and cysteine concentratins to control levels within 2 days. Bound homocysteine and cysteine and plasma free homocyst(e)ine concentrations in rats deficient in vitamin B-6 were in the same concentration range as those seen in patients with homocystinuria due to cystathionine β-synthase deficiency. Monitoring changes in plasma protein-bound and free homocysteine concentration during vitamin B-6 deficiency in rats may provide a useful system for the study of cystathionine β-synthase deficiency and its treatment.