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Homocysteine and thiol metabolites in vitamin B12 deficiency.

Abstract
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.
AuthorsL R Ranganath, M Baines, N B Roberts
JournalClinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 100 Issue 1 Pg. 111-6 (Jan 2001) ISSN: 0143-5221 [Print] England
PMID11115425 (Publication Type: Journal Article)
Chemical References
  • Sulfhydryl Compounds
  • Homocysteine
  • Dehydroepiandrosterone Sulfate
  • Glutathione Peroxidase
  • Cysteine
  • Vitamin B 12
Topics
  • Aged
  • Cysteine (blood)
  • Dehydroepiandrosterone Sulfate (blood)
  • Female
  • Glutathione Peroxidase (blood)
  • Homocysteine (blood)
  • Humans
  • Male
  • Middle Aged
  • Sulfhydryl Compounds (blood)
  • Vitamin B 12 (therapeutic use)
  • Vitamin B 12 Deficiency (blood, drug therapy)

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