Ethanol Inhibition of Methionine Synthase in Rat Liver and Cortex: Role of GSH Depletion and Different Cobalamin Cofactors

• Published in: The FASEB journal 2007-04, Vol.21 (5), p.A344-A345
• Main Authors: Waly, Mostafa Ibrahim‐Ahmed, Deth, Richard C., Kharbanda, Kusum K.
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.21.5.A344-d

Vitamin B12 is an essential cofactor for normal activity of the ubiquitous enzyme methionine synthase (MS), which methylates homocysteine as part of the methionine cycle. Studies have shown that chronic ethanol (ETOH) exposure in rats results in inhibition of MS and depletion of glutathione (GSH), the major intracellular antioxidant. We investigated the ability of either hydroxocobalamin (OHCbl) or methylcobalamin (MeCbl) to support MS activity. OHCbl is converted to MeCbl via a GSH‐dependent mechanism. In liver and cortex of the control animals, MeCbl‐based MS activity was higher than OHCbl‐based MS activity. ETOH treatment reduced both MeCb1 and OHCb1‐based MS activity in liver, however, in cortex ETOH reduced OHCb1‐based MS activity, but not MeCb1‐based activity. ETOH lowered liver and cortex GSH levels by 30%. Our results indicate that ethanol inhibits MS activity in both liver and cortex in conjunction with depleted intracellular GSH levels, but only in cortex was a unique protective effect for MeCbl observed against the ETOH‐mediated inhibition of MS activity. Thus intracellular oxidative stress may be responsible for the ETOH‐induced decrease in MS activity, and MeCb1 administration could represent a strategy to overcome this inhibitory effect.