Homocysteine and thiol metabolites in vitamin B-12 deficiency

Homocysteine metabolism is increasingly implicated in a diverse group of cl inical disorders, including atheromatous vascular disease. We studied the d isposition of homocysteine via the trans-sulphuration pathway, plasma gluta thione peroxidase (GPx) activity and plasma levels of the sulphated hormone dehydro-epiandrosterone sulphate (DHEAS) in six vitamin B-12-deficient hum an subjects before and after 2 weeks of vitamin B-12 repletion, both in the fasting state and following an oral methionine load (0.1 g/kg body weight) , pasting plasma total homocysteine concentrations fell (P = 0.03) and tota l cysteine concentrations rose significantly (P = 0.048) after treatment fo r 2 weeks with vitamin B-12 injections. The magnitude of the mean fall in t he fasting concentration of homocysteine (38.8 mu mol/l) was similar to the mean rise in cysteine levels (36.0 mu mol/l) following vitamin B-12 therap y. Circulating levels of homocysteine were increased at 4 h after a methion ine load when compared with fasting levels, both before and after vitamin B -12 repletion (P = 0.003 for both). Total cysteinyl-glycine was lower post- methionine than in the fasting state following vitamin B-12 therapy (P = 0. 007). Fasting plasma GPx fell significantly after 2 weeks of vitamin B-12 t herapy (P = 0.05). The change in plasma GPx between the fasting state and 4 h after methionine loading was significantly different pre- and post-vitam in B-12 therapy (P = 0.05). The present study provides indirect support to the hypothesis that defects in the trans-sulphuration and remethylation of homocysteine produce hyperhomocysteinaemia in vitamin B-12 deficiency in hu man subjects. Elevated homocysteine levels directly or indirectly may up-re gulate GPx. Sulphation status, as measured by plasma DHEAS, was unchanged.