Lactate, continued glycolysis

The lactate produced in the working muscle passes into the blood. Eventually, if strenuous exercise is continued, the concentration of lactate becomes so high that this fermentation can no longer continue. Glycolysis, and thus ATP production, stops. The muscle, deprived of energy, can no longer function. This point of exhaustion is called the anaerobic threshold. 

How does the formation of lactate permit glycolysis to continue under anaerobic conditions ... 

Under some conditions, the rate of glycolysis from glycogen to lactate plus protons can be greater than the capacity of the transporter to transport all the lactate and protons out of the muscle. In this case, they accumulate in the muscle and the pH falls to about 6.5 or even lower (Chapter 13). This can occur, for example, when a muscle is working close to maximum, or when there is a poor blood supply to a working muscle. If this continued for any length of time, the increase in proton concentration could be sufficient to damage some of the proteins in the muscle. Indeed, if this decrease in pH occurred in the blood, it would be very serious and could rapidly lead to death. This is prevented in two ways ... 

This metabolic scheme, which is called lactate fermentation, is shown in Fig. 11-7. The coreactant cycle between the two dehydrogenase enzymes, glyceraldehyde-3-phosphate dehydrogenase (Step 6) and lactate dehydrogenase, ensures that there is regeneration of NAD+ in this particular oxidation state so that glycolysis, lactate fermentation, and the production of ATP can continue. 

As in alcoholic fermentation, there is no net oxidation-reduction. The NADH formed in the oxidation of glyceraldehyde 3-phosphate is consumed in the reduction of pyruvate. The regeneration of NAD + in the reduction ofpyruvate to lactate or ethanol sustains the continued operation of glycolysis under anaerobic conditions. 

D. Inhibition of the electron transport chain shuts down the major pathway of regenerating NAD from the NADH produced in intermediary metabolism. This forces the cytosolic conversion of pyruvate to lactate to regenerate NAD+ so that glycolysis can continue in the absence of a functioning electron transport system. 

In the overview of glycolysis we noted that the pyruvate produced must be used up in some way so that the pathway will continue to produce ATP. Similarly, the NADH produced by glycolysis in step 6 (see Figure 21.8) must be reoxidized at a later time, or glycolysis will grind to a halt as the available NAD+ is used up. If the cell is functioning under aerobic conditions, NADH will be reoxidized, and pyruvate will be completely oxidized by aerobic respiration. Under anaerobic conditions, however, different types of fermentation reactions accomplish these purposes. Fermentations are catabolic reactions that occur with no net oxidation. Pyruvate or an organic compound produced from pyruvate is reduced as NADH is oxidized. We will examine two types of fermentation pathways in detail lactate fermentation and alcohol fermentation. 

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