Glycolytic flux

If the glycolytic flux is slow much of the pyruvate formed enters the mitochondria and is oxidized by the citrate cycle and reducing equivalents (2H) from NADH are oxidized indirectly (see below). When the flux is fast there is net production of... 

A decreased glycolytic rate has been proposed as a cause of muscle fatigue and related to pH inhibition of glycolytic enzymes. Decreasing pH inhibits both phosphorylase kinase and phosphofructokinase (PFK) activities. PFK is rate determining for glycolytic flux and therefore must be precisely matched to the rate of ATP expenditure. The essential characteristic of PFK control is allosteric inhibition by ATP. This inhibition is increased by H and PCr (Storey and Hochachka, 1974 ... 

Since more ATP is produced by respiration of glucose than by fermentation, and since the ATP requirement for biosynthesis of cell mass is the same, it follows that to obtain the same cell yield from glucose, the yeast should consume less sugar under aerobic conditions than under anaerobic conditions, with a resultant decrease in glycolytic flux (Berry, 1982). These phenomena are referred to as the Pasteur effect. Although this effect is observed in some yeasts, in S. cerevisiae it is either absent (Gancedo and Serrano, 1989) or observed only under certain nutrient-limited conditions. The main reason for the absence of the Pasteur effect is that even under aerobic conditions, fermentation is still the main catabolic route for the utilisation of glucose because of the Crabtree effect (Walker, 1994). The Crabtree effect is the repression... 

FIGURE 15-33 Dependence of glycolytic flux in a rat liver homogenate on added enzymes. Purified enzymes in the amounts shown on... 

Laties and associates589-592 provided evidence for an alternative, cyanide-resistant path of respiration in avocado mitochondria. Uncouplers were considered to stimulate glycolysis to the point where the glycolytic flux exceeds the oxidative capacity of the cytochrome pathway, with the result that the alternative pathway is engaged. However, these authors concluded that the alternative pathway is not required in order to sustain the elevated rate of respiration that characterizes the climacteric. Clarification of the role, if any, of this alternative pathway in fruit ripening awaits further study. 

Fig. 8.2 Glycolysis and related pathways. Glycolysis is a central metabolic machinery in which one mole of glucose is catabolized to two moles of pyruvate, NADH, and ATP. Under aerobic conditions, pyruvate is further oxidized by mitochondrial system. In erythrocytes DHAP is a dead-end product however, in brain it can be converted into direction of lipid synthesis. Glycolysis and the pentose phosphate pathway (pentosePP) are interconnected via fructose-6-P and glyceral-dehyde-3-P. A high level of NADPH favors lipid synthesis via pentose phosphate shunt (pentosePP). At TPI inhibition (TPI deficiency), glyceraldehyde-3-Pcan be produced via G6PDH as well, to contribute to the glycolytic flux. a-GDH catalyzes the...

Thomas, T., and D.A. Fell (1998). A control analysis exploration of the role of ATP utilization in glycolytic-flux control and glycolytic-metabolite-concentration regulation. Eur. J. Biochem. 259 956-967. 

Fig. 11-8 Gluconeogenesis and glycolysis. A, B, and C denote steps in gluconeogenesis that bypass irreversible glycolytic reactions (in the reverse direction to that of net glycolytic flux).

A good illustration of how glycolytic flux can rapidly change is seen when yeast are grown under aerobic and anaerobic conditions with glucose as the carbon source. This effect, first observed by Louis Pasteur, is called the Pasteur effect and is depicted in Fig. 11-21. 

Albert, M.A., Haanstra, J.R, Hannaert, V., Van Roy, J., Opperdoes, F.R., Bakker, B.M. and Michels, P.A. (2005) Experimental and in silico analyses of glycolytic flux control in bloodstream form Trypanosoma brucei. J. Biol. Chem. 280, 28306-28315. 

Snoep, J.L., Arfman, N., Yomano, L.P., Westerhoff, H.V., Conway, T. and Ingram, L.O. (1996) Control of glycolytic flux in Zymomonas mobilis by glucose-6-phosphate dehydrogenase activity. Biotechnol. Bioeng. 51, 190-197. 

Laughlin, M. R., and Thompson, D. (19%). The regulatory role for magnesium in glycolytic flux of the human erythrocyte. /. Biol. Chem. 271,28977-28983. 

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