Pyruvate fates

Acetyl-CoA is a potent allosteric effector of glycolysis and gluconeogenesis. It allosterically inhibits pyruvate kinase (as noted in Chapter 19) and activates pyruvate carboxylase. Because it also allosterically inhibits pyruvate dehydrogenase (the enzymatic link between glycolysis and the TCA cycle), the cellular fate of pyruvate is strongly dependent on acetyl-CoA levels. A rise in... 

The fate of the oxoacid is either (i) formation of a common intermediate of metabolism, i.e. an intermediate within a well-established metabolic pathway (e.g. oxaloacetate or pyruvate, in the above examples), or (ii) conversion to a common intermediate , e.g. oxoisocaproate is converted to acetyl-CoA (see Appendix 8.3). 

Figure 9.15 Fate of NADH produced in glycolysis. In hypoxic or anoxic conditions, pyruvate is converted to lactate with oxidation of NADH. In aerobic conditions, NADH is oxidised as shown in Figure 9.17 or 9.18 and pyruvate is oxidised via the Krebs cycle and the electron transfer chain.

The glycolytic pathway, or glycolysis, is a metabolic sequence in which glucose is broken down to pyruvic acid. The subsequent fate of pyruvate then depends upon whether or not the organism is aerobic or anaerobic Under aerobic conditions, pyruvate is oxidized via oxidative phosphorylation under anaerobic conditions, pyruvate is converted further into compounds such as lactate or ethanol, depending upon the organism. 

Fates of Pyruvate under Anaerobic Conditions Fermentation 538... 

In this chapter we describe the individual reactions of glycolysis, gluconeogenesis, and the pentose phosphate pathway and the functional significance of each pathway. We also describe the various fates of the pyruvate produced by glycolysis they include the fermentations that are used by many organisms in anaerobic niches to produce ATP and that are exploited industrially as sources of ethanol, lactic acid, and other... 

The oxidation of pyruvate is an important catabolic process, but pyruvate has anabolic fates as well. It can, for example, provide the carbon skeleton for the synthesis of the amino acid alanine. We return to these anabolic reactions of pyruvate in later chapters. 

FIGURE 14-3 Three possible catabolic fates of the pyruvate formed... 

Because cells maintain only limited amounts of NAD+, glycolysis would soon come to a halt if the NADH formed in this step of glycolysis were not continuously reoxidized. The reactions in which NAD+ is regenerated anaerobically are described in detail in Section 14.3, in our discussion of the alternative fates of pyruvate. 

We can now construct a balance sheet for glycolysis to account for (1) the fate of the carbon skeleton of glucose, (2) the input of P, and ADP and the output of ATP, and (3) the pathway of electrons in the oxidation-reduction reactions. The left-hand side of the following equation shows all the inputs of ATP, NAD+, ADP, and Pj (consult Fig. 14-2), and the right-hand side shows all the outputs (keep in mind that each molecule of glucose yields two molecules of pyruvate) ... 

This three-step process for transferring fatty acids into the mitochondrion—esterification to CoA, transesterification to carnitine followed by transport, and transesterification back to CoA—links two separate pools of coenzyme A and of fatty acyl-CoA, one in the cytosol, the other in mitochondria These pools have different functions. Coenzyme A in the mitochondrial matrix is largely used in oxidative degradation of pyruvate, fatty acids, and some amino acids, whereas cytosolic coenzyme A is used in the biosynthesis of fatty acids (see Fig. 21-10). Fatty acyl-CoA in the cytosolic pool can be used for membrane lipid synthesis or can be moved into the mitochondrial matrix for oxidation and ATP production. Conversion to the carnitine ester commits the fatty acyl moiety to the oxidative fate. 

Acetyl-CoA is a critical regulator of the fate of pyruvate it allosterically inhibits pyruvate dehydrogenase and stimulates pyruvate carboxylase (see Fig. 15-20). In these ways acetyl-CoA prevents it own further production from pyruvate while stimulating the conversion of pyruvate to oxaloacetate, the first step in gluconeo-genesis. 

Alternate fates of pyruvate Compounds other than lactate to which pyruvate can be converted ALTERNATE FATES OF PYRUVATE (p. 103) Pyruvate can be oxidatively decarboxylated by pyruvate dehydrogenase, producing acetyl CoA—a major fuel for the tricarboxylic acid cycle (TCA cycle) and the building block for fatty acid synthesis. Pyruvate can be carboxylated to oxaloacetate (a TCA cycle intermediate) by pyruvate carboxylase. Pyruvate can be reduced by microorganisms to ethanol by pyruvate decarboxylase. 

The product of this metabolic sequence, pyruvate, is a metabolite of caitral importance. Its fate depends upon the conditions within a cell and upon the type of cell. When oxygen is plentiful pyruvate is usually converted to acetyl-coenzyme A, but under anaerobic conditions it may be reduced by NADH + H+ to the alcohol lactic acid (Fig. 10-3, step h). This reduction exactly balances the previous oxidation step, that is, the oxidation of glycer-aldehyde 3-phosphate to 3-phospho-glycerate (steps a and b). With a balanced sequence of an oxidation reaction, followed by a reduction reaction, glucose can be converted to lactate in the absence of oxygen, a fermentation process. The lactic acid fermentation occurs not only in certain bacteria but also in our own muscles under conditions of extremely vigorous exercise. It also occurs continuously in some tissues, e.g., the transparent lens and cornea of the eye. 

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