Stoichiometry and compartmentation of NADH metabolism in Saccharomyces cerevisiae

In Saccharomyces cerevisiae, reduction of NAD(+) to NADH occurs in dissimil atory as well as in assimilatory reactions. This review discusses mechanism s for reoxidation of NADH in this yeast, with special emphasis on the metab olic compartmentation that occurs as a consequence of the impermeability of the mitochondrial inner membrane for NADH and NAD(+). At least five mechan isms of NADH reoxidation exist in S. cerevisiae. These are: (1) alcoholic f ermentation; (?) glycerol production; (3) respiration of cytosolic NADH via external mitochondrial NADH dehydrogenases 1 (4) respiration of cytosolic NADH via the glycerol-3-phosphate shuttle, and (5) oxidation of intramitoch ondrial NADH via a mitochondrial 'internal' NADH dehydrogenase. Furthermore , in vivo evidence indicates that NADH redox equivalents can be shuttled ac ross the mitochondrial inner membrane by an ethanol-acetaldehyde shuttle. S everal other redox-shuttle mechanisms might occur in S. cerevisiae, includi ng a malate-oxaloacetate shuttle? a malate-aspartate shuttle and a malate-p yruvate shuttle. Although key enzymes and transporters for these shuttles a re present, there is as yet no consistent evidence for their in vivo activi ty. Activity of several other shuttles. including the malate-citrate and fa tty acid shuttles, can be ruled out based on the absence of key enzymes or transporters. Quantitative physiological analysis of defined mutants has be en important in identifying several parallel pathways for reoxidation of cy tosolic and intramitochondrial NADH. The major challenge that lies ahead is to elucidate the physiological function of parallel pathways for NADH oxid ation in wild-type cells, both under steady-state and transient-state condi tions. This requires the development of techniques for accurate measurement of intracellular metabolite concentrations in separate metabolic compartme nts. (C) 2001 Federation of European Microbiological Societies, Published b y Elsevier Science B.V. All rights reserved.