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Deficiency in Cytosolic Malic Enzyme Does Not Increase Acetaminophen‐Induced Hepato‐Toxicity
Author(s) -
Qian Su,
Mumick Sheena,
Nizner Peter,
Tota Michael R.,
Menetski Joseph,
Reitman Marc L.,
MacNeil Douglas J.
Publication year - 2008
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2008.00228.x
Subject(s) - glutathione , malic enzyme , detoxification (alternative medicine) , oxidative decarboxylation , biochemistry , nicotinamide adenine dinucleotide phosphate , chemistry , enzyme , acetaminophen , toxicity , glutathione reductase , cytosol , dehydrogenase , glutathione peroxidase , medicine , alternative medicine , organic chemistry , pathology , oxidase test
Cytosolic malic enzyme (ME‐1) is a nicotinamide adenine dinucleotide phosphate (NADP)‐dependent enzyme that generates NADPH. The activity of this enzyme, the reversible oxidative decarboxylation of malate to yield pyruvate, links glycolytic pathway to citric acid cycle. The high level of ME‐1 expression in liver, and its involvement in NADPH production, suggests reduced ME‐1 activity might compromise hepatic production of reduced glutathione (GSH) by the NADPH‐dependent enzyme glutathione reductase, and hence affect xenobiotic detoxification. The role of ME‐1 in liver detoxification was evaluated in Mod1 deficient mice ( mod1 −/– ) by evaluating their sensitivity to acetaminophen‐induced liver injury. The results show that mod1 −/– mice are not more sensitive to acetaminophen hepato‐toxicity. Although GSH levels were initially depleted more in the mod1 −/– liver than in wild‐type controls, the GSH levels recovered quickly. In conclusion, our data indicate that ME‐1 deficiency does not adversely affect GSH‐dependent detoxification.