Regulation of Glucose Metabolism in Growing Yeast Cells

Fiechter, Armin; Fuhrmann, Günter Fred; Käppeli, Othmar

doi:10.1016/s0065-2911(08)60327-6

Cited by 310 publications

(141 citation statements)

References 129 publications

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“…In S. cerevisiae, overflow metabolism begins when the specific glucose uptake rate (or the glycolytic flux) exceeds a threshold rate, and the result is the formation of ethanol and glycerol (7)(8)(9)(10). One hypothesis is that this overflow is due to a limitation in capacity of the respiratory pathways (8,11).…”

mentioning

confidence: 99%

Increasing NADH oxidation reduces overflow metabolism in Saccharomyces cerevisiae

Vemuri

Eiteman

McEwen

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

321

273

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Respiratory metabolism plays an important role in energy production in the form of ATP in all aerobically growing cells. However, a limitation in respiratory capacity results in overflow metabolism, leading to the formation of byproducts, a phenomenon known as ''overflow metabolism'' or ''the Crabtree effect.'' The yeast Saccharomyces cerevisiae has served as an important model organism for studying the Crabtree effect. When subjected to increasing glycolytic fluxes under aerobic conditions, there is a threshold value of the glucose uptake rate at which the metabolism shifts from purely respiratory to mixed respiratory and fermentative. It is well known that glucose repression of respiratory pathways occurs at high glycolytic fluxes, resulting in a decrease in respiratory capacity. Despite many years of detailed studies on this subject, it is not known whether the onset of the Crabtree effect is due to limited respiratory capacity or is caused by glucose-mediated repression of respiration. When respiration in S. cerevisiae was increased by introducing a heterologous alternative oxidase, we observed reduced aerobic ethanol formation. In contrast, increasing nonrespiratory NADH oxidation by overexpression of a water-forming NADH oxidase reduced aerobic glycerol formation. The metabolic response to elevated alternative oxidase occurred predominantly in the mitochondria, whereas NADH oxidase affected genes that catalyze cytosolic reactions. Moreover, NADH oxidase restored the deficiency of cytosolic NADH dehydrogenases in S. cerevisiae. These results indicate that NADH oxidase localizes in the cytosol, whereas alternative oxidase is directed to the mitochondria.alternative oxidase ͉ Crabtree effect ͉ NADH oxidase ͉ redox metabolism R edox homeostasis is a fundamental requirement for sustained metabolism and growth in all biological systems. The intracellular redox potential is primarily determined by the NADH/NAD ratio and to a lesser extent by the NADPH/NADP ratio. In Saccharomyces cerevisiae, Ͼ200 reactions involve these cofactors spread over a large spectrum of cellular functions (1). Because NADH is a highly connected metabolite in the metabolic network (1), any change in the NADH/NAD ratio leads to widespread changes in metabolism (2). NADH is generated primarily in the cytosol by glycolysis and in the mitochondria by the tricarboxylic acid (TCA) cycle. Because the NADH/NAD redox couple cannot traverse the mitochondrial membrane in S. cerevisiae and other eukaryotic cells (3), distinct mechanisms oxidize NADH to NAD in the cytosol and mitochondria. Cytosolic NADH is oxidized by two external (cytosolic) mitochondrial membrane-bound NADH dehydrogenases encoded by NDE1 and NDE2 genes with catalytic sites facing the cytosol (4). Additionally, glycerol-3-phosphate dehydrogenases (encoded by GPD1 and GPD2) oxidize cytosolic NADH with concomitant glycerol formation when the NADH formation rate surpasses its oxidation rate (5). Mitochondrial NADH is oxidized by one internal mitochondrial membrane-bound NADH dehydrogena...

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mentioning

confidence: 99%

Increasing NADH oxidation reduces overflow metabolism in Saccharomyces cerevisiae

Vemuri

Eiteman

McEwen

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

321

273

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“…This aerobic fermentation process, referred to as the Crabtree effect (De Deken, 1966 (Polakis et al, 1964;Lowden et al, 1972;Fiechter et al, 1981). The overall effects of carbohydrate repression, however, are still not clearly understood.…”

Section: Resultsmentioning

confidence: 99%

Carbohydrate repression effects in the high corn ethanol fermentation system

Ziffer

1983

Biotechnol Lett

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“…The ability to obtain such high ethanol yields in 24-48 hr under production conditions, would require careful control of the S. cerevisiae metabolic regulatory factors which are mediated, in part, by cell viability (9,10), alcohol toxicity (11-13), transport activity (14,15), and substrate and osmotic repression effects (1)(2)(3)16,17). In the high corn fermentation, the critical mediating conditions appear to involve carbohydrate and osmotic effects, so it is important to understand these regulatory phenomena in order to develop a viable process.…”

Section: And Discussionmentioning

confidence: 99%

Ammonium acceleration of glycolysis in the ethanol fermentation in a high corn system.

Ziffer¹

1986

J. Gen. Appl. Microbiol.

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Regulation of Glucose Metabolism in Growing Yeast Cells

Cited by 310 publications

References 129 publications

Increasing NADH oxidation reduces overflow metabolism in Saccharomyces cerevisiae

Increasing NADH oxidation reduces overflow metabolism in Saccharomyces cerevisiae

Carbohydrate repression effects in the high corn ethanol fermentation system

Ammonium acceleration of glycolysis in the ethanol fermentation in a high corn system.

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