Reference : Occurrence and subcellular distribution of the NAD(P)HX repair system in mammals.
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Occurrence and subcellular distribution of the NAD(P)HX repair system in mammals.
Marbaix, Alexandre Y. [> >]
Tyteca, Donatienne [> >]
Niehaus, Tom D. [> >]
Hanson, Andrew D. [> >]
Linster, Carole mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Van Schaftingen, Emile [> >]
The Biochemical journal
Yes (verified by ORBilu)
[en] Alternative Splicing/genetics ; Amino Acid Sequence ; Animals ; CHO Cells ; Carrier Proteins/genetics/metabolism ; Cricetinae ; Cricetulus ; Cytosol/enzymology ; DNA Repair/genetics ; Endoplasmic Reticulum/enzymology/genetics ; HEK293 Cells ; Humans ; Mice ; Mitochondria/enzymology/genetics ; Molecular Sequence Data ; NADP/genetics/metabolism ; Phosphoproteins/genetics/metabolism ; Phosphotransferases (Alcohol Group Acceptor)/chemistry/genetics ; Rats ; Subcellular Fractions/enzymology ; Tissue Distribution/genetics ; Transcription Factors/chemistry/genetics
[en] Hydration of NAD(P)H to NAD(P)HX, which inhibits several dehydrogenases, is corrected by an ATP-dependent dehydratase and an epimerase recently identified as the products of the vertebrate Carkd (carbohydrate kinase domain) and Aibp (apolipoprotein AI-binding protein) genes respectively. The purpose of the present study was to assess the presence of these enzymes in mammalian tissues and determine their subcellular localization. The Carkd gene encodes proteins with a predicted mitochondrial propeptide (mCARKD), a signal peptide (spCARKD) or neither of them (cCARKD). Confocal microscopy analysis of transfected CHO (Chinese-hamster ovary) cells indicated that cCARKD remains in the cytosol, whereas mCARKD and spCARKD are targeted to the mitochondria and the endoplasmic reticulum respectively. Unlike the other two forms, spCARKD is N-glycosylated, supporting its targeting to the endoplasmic reticulum. The Aibp gene encodes two different proteins, which we show to be targeted to the mitochondria (mAIBP) and the cytosol (cAIBP). Quantification of the NAD(P)HX dehydratase and epimerase activities in rat tissues, performed after partial purification, indicated that both enzymes are widely distributed, with total activities of approximately 3-10 nmol/min per g of tissue. Liver fractionation by differential centrifugation confirmed the presence of the dehydratase and the epimerase in the cytosol and in mitochondria. These data support the notion that NAD(P)HX repair is extremely widespread.
Luxembourg Centre for Systems Biomedicine (LCSB): Enzymology & Metabolism (Linster Group)

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