Cytosolic Adaptations to an Anaerobic Energy Metabolism

Some eukaryotes can survive hypoxia by using simple fermentations in which the electrons from glycolysis are transferred to pyruvate or a derivative of it. Many variations of this type of fermentation exist, resulting in end products such as lactate or ethanol (Fig. 5.1). The formation of lactate produces 2 mol of ATP per glucose degraded, is found in all phyla, and it is the sole anaerobic pathway of evolutionarily more advanced species like arthropoda and vertebrates (Livingstone 1991).

Conversion of pyruvate into ethanol is a variant of cytosolic fermentation, which occurs, for instance, in yeast and hypoxia-tolerant fish, such as crucian carp and goldfish (van Waarde et al. 1993; Lutz and Nilsson 1997). Ethanol can be formed from pyruvate via two distinct pathways. The most common pathway for ethanol production, which is present in yeast, consists of a decarboxylation of pyruvate to acetaldehyde by pyruvate decarboxylase followed by reduction to ethanol by alcohol dehydrogenase (Fig. 5.1). However, ethanol can also be formed from pyruvate via acetylcoenzyme A (acetyl-CoA), a pathway in which pyruvate is first oxidatively decarboxylated to acetyl-CoA, which is then reduced in two subsequent reactions by acetalde-hyde dehydrogenase and alcohol dehydrogenase. This pathway occurs, for example, in the human intestinal parasites Giardia lamblia and Entamoeba histolytica, where pyruvate is oxidized by pyruvate:ferredoxin oxidoreduc-tase (PFO), which yields acetyl-CoA and carbon dioxide, like the mitochondrial reaction catalysed by pyruvate dehydrogenase (PDH) (Horner et al. 1999). However, in the case of Giardia and Entamoeba, ferredoxin acts as electron acceptor and not NAD+, as is the case in the reaction catalysed by PDH. The reduced ferredoxin donates the electrons to H+, resulting in the formation of hydrogen. In G. lamblia and E. histolytica, which lack energy-generating organelles, the acetyl-CoA formed is further degraded in the cytosol into a mixture of ethanol and acetate (Fig. 5.1). The ethanol is produced by an alcohol dehydrogenase E (ADH-E), a bifunctional enzyme that combines aldehyde dehydrogenase and alcohol dehydrogenase activities (Bruchhaus and Tannich 1994; Sanchez 1998). Acetate is produced by acetyl-CoA synthase with the concomitant production of ATP. The extra ATP produced by this further degradation of pyruvate fluctuates between 0 and 2 mol of ATP per glucose degraded, as the relative amounts of ethanol and acetate produced depend on environmental conditions (Lloyd 1996; Müller 1998; Martin 2000).

Another cytosolic fermentation variant is found in several trichomonad and yeast species, which increase their glycerol production during anoxia (Steinbüchel and Müller 1986; Valadi et al. 2004). In this case, the glycolytic intermediate dihydroxyacetone phosphate (DHAP) is converted to glycerol-3-phosphate by an NADH-dependent glycerol-3-phosphate dehydrogenase and subsequently to glycerol by glycerol kinase (Fig. 5.1). Glycerol production from glucose thus results in net consumption of NADH, and it is essential in respiratory-incompetent yeast cells (Valadi et al. 2004).

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