Glycolysis pyruvate, fate

FIGURE 14-3 Three possible catabolic fates of the pyruvate formed in glycolysis. Pyruvate also serves as a precursor in many anabolic reactions, not shown here. 

The fate of pyruvate depends on the route used for NADH oxidation. If NADH is reoxidized in a shuttle system, pyruvate can be used for other pathways, one of which is oxidation to acetyl-CoA and entry into the TCA cycle for complete oxidation. Alternatively, in anaerobic glycolysis, pyruvate is reduced to lactate and diverted away from other potential pathways. Thus, the use of the shuttle systems allows for more ATP to be generated than by anaerobic glycolysis by both oxidizing the cytoplasmically derived NADH in the electron transport chain and by allowing pyruvate to be oxidized completely to CO2. 

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... 

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. 

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... 

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) ... 

Fig. 1. The reactions of glycolysis (glucose to pyruvate) plus fates of pyruvate.

Fates of pyruvate Entry into the citric acid cycle. Glycolysis releases relatively little of the... 

Most cestodes which have been investigated, however, conform to the second category, type 2, which is characterised by a C02-fixation step. Carbohydrate is degraded to the level of PEP by glycolysis, the steps involved being similar to those in mammalian tissue. At this point, the enzymes pyruvate kinase and phosphoenolpyruvate carboxykinase (PEPCK) compete for available substrate and a branch-point occurs (Fig. 5.4). The relative activities of these two enzymes determine the fate of the PEP and the subsequent types and amounts of end-products formed (see below). 

A third fate of pyruvate is its carboxylation to oxaloacetate inside mitochondria, the first step in gluconeogenesis. This reaction and the subsequent conversion of oxaloacetate into phosphoenolpyruvate bypass an irreversible step of glycolysis and hence enable glucose to be synthesized from pyruvate. The carboxylation of pyruvate is also important for replenishing intermediates of the citric acid cycle. Acetyl CoA activates pyruvate carboxylase, enhancing the synthesis of oxaloacetate, when the citric acid cycle is slowed by a paucity of this intermediate. 

The fate of pyruvate formed by glycolysis differs among species, and within the same species depending on the level of oxygen available for further oxidation of the products of glycolysis. 

The major fate of glucose 6-phosphate is to enter the pathway of glycolysis, which produces pyruvate and generates NADH and ATP. 

In tissues other than the RBC, pyruvate has alternative metabolic fates that, depending on the tissue, include gluconeogenesis, conversion to acetyl-CoA by pyruvate dehydrogenase for further metabolism to CO in the tricarboxylic acid (TCA) cycle, transamination to alanine or carboxylation to oxaloacetate by pyruvate carboxylase (Table 23-1). In the RBC, however, the restricted enzymatic endowment precludes all but the conversion to lactate. The pyruvate and lactate produced are end products of RBC glycolysis that are transported out of the RBC to the liver where they can undergo the alternative metabolic conversions described above. 

Phosphoglucomutase converts glucose-l-phosphate into glucose-6-phosphate which has several metabolic fates. It is for example a precursor in the pentose phosphate pathway (PPP), it can be converted to a-D-glucose and to pyruvate via the glycolysis pathway (see Figure 9.2). 

Two pyruvate molecules. At the end of glycolysis the six-carbon glucose molecule has been converted into two three-carbon pyruvate molecules. The fate of the p)rruvate also depends on whether the reactions are occurring in the presence or absence of oxygen. Under aerobic conditions it is used to produce acetyl CoA destined for the citric acid cycle and complete oxidation. Under anaerobic conditions it is used as an electron acceptor in fermentation reactions. 

---