Thiamine (vitamin B1) supplementation does not reduces fasting blood homocysteine concentration in most homozygotes for homocystinuria

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1317

Article

Franken, DG ; Blom, HJ ; Boers, GHJ ; Tangerman, A ; Thomas, CMG ; Trijbels, FJM

关键词: homocysteine;    homocystinuria;    thiamine;    transamination;    vitamin B1;   

DOI  :  10.1016/S0925-4439(96)00033-6

来源: Elsevier

【 摘 要 】

Homozygotes for homocystinuria due to cystathionine synthase (CS) deficiency accumulate homocysteine and methionine in their blood and tissues. High-dose pyridoxin, folic acid, vitamin B12, or betaine are therapeutical options to lower the elevated homocysteine concentration. These compounds stimulate the transsulfuration or remethylation of homocysteine. Despite such treatment, elevated blood homocysteine concentrations may persist in many homocystinurics. Therefore, it is warranted to study alternative regimen to reduce the blood homocysteine concentration in homocystinurics. Apart from entering the transsulfuration pathway, methionine can be catabolized via the transamination pathway, by conversion into 4-methylthio-2-oxobutyrate (MTOB), followed by oxidative decarboxylation of MTOB to 3-methylthiopropionate. Thiamine pyrophosphate, the active form of thiamine, is a cofactor of the supposed rate-limiting oxidative decarboxylation in the transamination of methionine. The effect of thiamine administered in 2 or 3 daily doses of 25 mg orally, was studied in nine homozygote CS deficient patients. Methionine levels decreased in 6 out of 9 patients. In 8 out of 9 patients, however, the levels of plasma homocysteine remained virtually unchanged, as did the serum transamination metabolites in all patients. We conclude that vitamin B1 cannot be used as an additional homocysteine-lowering treatment in most homozygotes for homocystinuria.

【 授权许可】

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