ビタミンB_<12>欠乏によるアミノ酸代謝異常とその分子的作用機序の解明

抄録

Vitamin B_<12> (B_<12>) is an essential nutrient and functions as the coenzyme for methylmalonyl-CoA mutase and methionine synthase in mammals. B_<12> deficiency has been reported to cause growth retardation and severe hematological and neurological abnormalities. However, the biochemical mechanisms for these abnormalities caused by B_<12> deficiency are poorly understood. In the present study, therefore, metabolic abnormalities caused by B_<12> deficiency were examined using B_<12>-deficient rats as an experimental B_<12>-deficient model. The following findings were indicated in this study; (1) amino acid metabolism in rats was disordered by B_<12> deficiency and, in particular, serine and threonine in the plasma and urine were abnormally increased by the deficiency, (2) the expression of serine dehydratase participating in the metabolism of serine and threonine in liver was significantly lowered by B_<12> deficiency without no direct involvement of B_<12> in the enzyme reaction, (3) these abnormalities were consequently induced by impairment of glucagon signal transduction activating adenylyl cyclase system. In addition, it was found that a megaloblastic anaemia-like symptom was induced when the B_<12> deficient rats were exposed to hypoxia.