Cobalamin deficiency results in an abnormal increase in L-methylmalonyl-co-enzyme-A mutase expression in rat liver and COS-7 cells

The British Journal of Nutrition
Motoyuki NakaoYoshihisa Nakano

Abstract

The aim of the present study was to examine the effects of cobalamin (Cbl) on the activity and expression of L-methylmalonyl-CoA mutase (MCM) in rat liver and cultured COS-7 cells. The MCM holoenzyme activity was less than 5% of the total (holoenzyme+apoenzyme) activity in the liver although rats were fed a diet containing sufficient Cbl. When weanling rats were maintained on a Cbl-deficient diet, the holo-MCM activity became almost undetectable at the age of 10 weeks. In contrast, a marked increase in the total-MCM activity occurred under the Cbl-deficient conditions, and at the age of 20 weeks it was about 3-fold higher in the deficient rats than in the controls (108 (SD 14.5) v. 35 (SD 8.5) nmol/mg protein per min (n 5); P<0.05). Western blot analysis confirmed that the MCM protein level increased significantly in the Cbl-deficient rats. However, the MCM mRNA level, determined by real-time PCR, was rather decreased. When COS-7 cells were cultured in a medium in which 10% fetal bovine serum was the sole source of Cbl, holo-MCM activity was barely detected. The supplementation of Cbl resulted in a large increase in the holo-MCM activity in the cells, but the activity did not exceed 30% of the total-MCM activity even in the pre...Continue Reading

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Citations

Oct 6, 2009·Journal of Neurochemistry·Giuseppe Scalabrino
Aug 4, 2016·Experimental Biology and Medicine·Tomohiro Bito, Fumio Watanabe
Jul 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tomohiro BitoFumio Watanabe
Jun 4, 2020·Genes·Nataliya KozhukharMikhail F Alexeyev

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