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 B12-deficient human subjects before and after 2 weeks of vitamin B12 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 B12 injections. The magnitude of the mean fall in the fasting concentration of homocysteine (38.8 µmol/l) was similar to the mean rise in cysteine levels (36.0 µmol/l) following vitamin B12 therapy. Circulating levels of homocysteine were increased at 4 h after a methionine load when compared with fasting levels, both before and after vitamin B12 repletion (P = 0.003 for both). Total cysteinyl-glycine was lower post-methionine than in the fasting state following vitamin B12 therapy (P = 0.007). Fasting plasma GPx fell significantly after 2 weeks of vitamin B12 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 B12 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 B12 deficiency in human subjects. Elevated homocysteine levels directly or indirectly may up-regulate GPx. Sulphation status, as measured by plasma DHEAS, was unchanged.
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Research Article| December 13 2000
Homocysteine and thiol metabolites in vitamin B12 deficiency
L. R. RANGANATH;
*Department of Chemical Pathology, Epsom General Hospital, Epsom, Surrey KT18 7EG, U.K.
Correspondence: Dr L. Ranganath, Department of Clinical Chemistry, Royal Liverpool University Hospital, Prescot Street, Liverpool L7 8XP, U.K. (e-mail firstname.lastname@example.org).
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L. R. RANGANATH, M. BAINES, N. B. ROBERTS; Homocysteine and thiol metabolites in vitamin B12 deficiency. Clin Sci (Lond) 1 January 2001; 100 (1): 111–116. doi: https://doi.org/10.1042/cs1000111
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