Homocysteine and thiol metabolites in vitamin B12 deficiency.
Homocysteine metabolism is increasingly implicated in a diverse group of clinical disorders, including atheromatous vascular disease. We studied the disposition of homocysteine via the trans-sulphuration pathway, plasma glutathione peroxidase (GPx) activity and plasma levels of the sulphated hormone dehydro-epiandrosterone sulphate (DHEAS) in six vitamin B(12)-deficient human 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). Fasting plasma total homocysteine concentrations fell (P=0.03) and total cysteine concentrations rose significantly (P=0.048) after treatment for 2 weeks with vitamin B(12) injections. The magnitude of the mean fall in the fasting concentration of homocysteine (38.8 micromol/l) was similar to the mean rise in cysteine levels (36.0 micromol/l) following vitamin B(12) therapy. Circulating levels of homocysteine were increased at 4 h after a methionine 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) therapy (P=0.05). The change in plasma GPx between the fasting state and 4 h after methionine loading was significantly different pre- and post-vitamin 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 human subjects. Elevated homocysteine levels directly or indirectly may up-regulate GPx. Sulphation status, as measured by plasma DHEAS, was unchanged.
Ranganath
L R
LR
Department of Chemical Pathology, Epsom General Hospital, Epsom, Surrey KT18 7EG, UK. lrang@liv.ac.uk
Baines
M
M
Roberts
N B
NB
D000368:Aged; D003545:Cysteine / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013438:Sulfhydryl Compounds / Q000097:blood*; D014805:Vitamin B 12 / Q000627:therapeutic use; D014806:Vitamin B 12 Deficiency / Q000097:blood* / Q000188:drug therapy
D013438:Sulfhydryl Compounds; D006710:Homocysteine; D019314:Dehydroepiandrosterone Sulfate; D005979:Glutathione Peroxidase; D003545:Cysteine; D014805:Vitamin B 12