The role of malic enzyme as the provider of NADPH in oleaginous microorganisms: a reappraisal and unsolved problems
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Malic enzyme (ME; NADP+-dependent; EC 1.1.40) provides NADPH for lipid biosynthesis in oleaginous microorganisms. Its role in vivo depends on there being an adequate supply of NADH to drive malate dehydrogenase to convert oxaloacetate to malate as a component of a cycle of three reactions: pyruvate → oxaloacetate → malate and, by the action of ME, back to pyruvate. However, the availability of cytosolic NADH is limited and, consequently, ancillary means of producing NADPH are necessary. Stoichiometries are given for the conversion of glucose to triacylglycerols involving ME with and without the reactions of the pentose phosphate pathway (PPP) as an additional source of NADPH. Some oleaginous microorganisms (such as Yarrowia lipolytica), however, lack a cytosolic ME and, if the PPP is the sole provider of NADPH, the theoretical yield of triacylglycerol from glucose falls to 27.6 % (w/w) from 31.6 % when ME is present. An alternative route for NADPH generation via a cytosolic isocitrate dehydrogenase (NADP+-dependent) is then discussed.
KeywordsGlucose metabolism Fatty acid biosynthesis Isocitrate dehydrogenase Lipid accumulation Malic enzyme Pentose phosphate pathway Stoichiometries
I owe a debt of gratitude to Professor Hans van Dijken, The Netherlands, for returning my attention to the unsolved problem of NADPH generation in oleaginous microorganisms that had been highlighted in an earlier review of mine (Ratledge 1997) but then had been somewhat conveniently forgotten in subsequent discussions of this topic. I am also indebted to him for a critical appraisal of the first draft of this review and for bringing to my attention some of the key papers involving the possible synthesis of isocitrate from 2-oxoglutarate in mammalian systems. Any remaining errors and oversights are entirely my own.
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