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superpathway NAD/NADP - NADH/NADPH interconversion

:NAD and its reduced and phosphorylated derivatives are essential metabolites in all organisms and are, except for protons, water and oxygen, integrated with more biochemical reactions than any other biochemical agent . As major players involved in energy metabolism, electron transfer and indispensable metabolic cycles the various :NAD species have attracted much attention and generated significant research efforts in elucidating their specific roles in relevant catalyses. In addition, there is growing evidence that :NAD species also operate in signaling pathways . In Saccharomyces cerevisiae the interconvertibility of the various :NAD species is of utmost importance for maintaining the redox balance of the cells which, in turn determines growth efficiency and metabolite excretion . The various pyridine nucleotides, in particular :NADH cannot permeate the inner membrane of mitochondrion. For that reason direct transversal exchanges of :NAD and reduced and/or phosphorylated derivatives from the cytosol to the mitochondria and vice versa are not possible. Moreover, yeast does not possess transhydrogenases, hence cannot directly convert :NAD and :NADPH into :NADP and :NADH . Consequently, to ensure the availability of the required :NAD metabolites in each organelle, yeast has developed independent sets of interconversion reactions that provide the supply of all :NAD types through various enzymatic reactions. In the cytoplasm two NAD kinases have been characterized that can phosphorylate :NAD. The main cytosolic NAD kinase is encoded by UTR1 . A second, less important NAD kinase for phosphorylation of :NAD, i.e. YEF1 has also been described and shown to compensate for the loss of UTR1 . The deletion of both the mitochondrial POS5 (see : PWY-7269-YEAST) and cytosolic UTR1 (see :PWY-7268) is lethal in yeast and YEF1 can only compensate when POS5 still operates. These findings support the notion that the main NADH kinases of yeast, i.e. POS5 and UTR1 can partially compensate for the loss of one's respective activity . Both UTR1 and YEF1 have been shown to exhibit NADH kinase activity as well providing the cytosolic set of enzymes with the catalytic ability to phosphorylate :NADH . Various enzymatic reactions have been shown to account for the provision of the cytosol with :NADPH required for biosynthetic pathways and anti-oxidant functions. The cytosolic acetaldehyde dehydrogenase encoded by ALD6 and the glucose-6-phosphate dehydrogenase (ZWF1) catalyzing the first step in the :PENTOSE-P-PWY to convert :GLC-6-P to :D-6-P-GLUCONO-DELTA-LACTONE are considered as the main suppliers of :NADPH. A third enzyme producing :NADPH in the cytoplasm is the cytosolic NADP-dependent isocitrate dehydrogenase (IDP2) . It has been demonstrated that ZWF1 has overlapping functions with the isocitrate dehydrogenase (IDP2) and the acetaldehyde oxidoreductase (ALD6) indicating the compensation for the deficiency of :NADPH should one of the involved reactions fail to operate . In the mitochondria of Saccharomyces two main sources for the generation of :NADPH have been proposed. The NADH kinase encoded by the POS5 gene is considered to be the main provider of :NADPH in the mitochondrion by phosphorylation of :NADH. However, since POS5 also works as NAD kinase this reaction followed by the dehydrogenase reaction of :MONOMER-13666/:MONOMER-13665 is the other source for the synthesis of :NADPH in Saccharomyces mitochondria . The oxidation of cytosolic :NADH via the mitochondrial respiration chain is catalyzed by three NADH:ubiquinone oxidoreductases, one internal, i.e. NDI1 and two external, i.e. NDE1/NDE2 . The malate-aspartate shuttle in coordination with the 2 external NADH:ubiquinone oxidoreductases is also considered to contribute to the reoxidation of cytosolic :NADH .

from BIOCYC source record: YEAST_PWY-7245
Type: pathway
Taxonomic scope
organism-specific biosystem
Saccharomyces cerevisiae

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