Pyruvate aerobic conditions

In 1937, Alexander E. Braunstein (1902-86), working in Moscow, was studying the metabolism of glutamate in muscles and made the interesting observation that when glutamate levels decrease so do lactate (anaerobic conditions) or pyruvate (aerobic conditions). In each case the concentrations of alanine increase. He had discovered the reversible transamination reactions that connect the intermediary metabolisms of proteins and carbohydrates. 

The growth of Bacillus subtilis may take place under a variety of conditions (a) aerobic conditions, (b) using nitrate as electron acceptor, and (c) fermentative conditions with glucose provided pyruvate is available as an electron acceptor since the organism lacks pyruvate formate hydrogen lyase (Nakano and Zuber 1998). 

Under aerobic conditions, the hydrogen atoms of NtUDH are oxidised within the mitochondrion pyruvate is also oxidised in the mitochondrion (Figure 9.15). However, NADH cannot be transported across the inner mitochondrial membrane, and neither can the hydrogen atoms themselves. This problem is overcome by means of a substrate shuttle. In principle, this involves a reaction between NADH and an oxidised substrate to produce a reduced product in the cytosol, followed by transport of the reduced product into the mitochondrion, where it is oxidised to produce hydrogen atoms or electrons, for entry into the electron transfer chain. Finally, the oxidised compound is transported back into the cytosol. The principle of the shuttle is shown in Figure 9.16. 

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. 

D. In most cells, oxygen serves as the final acceptor of electrons removed during pyruvate synthesis (aerobic conditions). 

When animal tissues cannot be supplied with sufficient oxygen to support aerobic oxidation of the pyruvate and NADH produced in glycolysis, NAD+ is regenerated from NADH by the reduction of pyruvate to lactate. As mentioned earlier, some tissues and cell types (such as erythrocytes, which have no mitochondria and thus cannot oxidize pyruvate to C02) produce lactate from glucose even under aerobic conditions. The reduction of pyruvate is catalyzed by lactate dehydrogenase, which forms the l isomer of lactate at pH 7 ... 

Under aerobic conditions, the glycolytic pathway becomes the initial phase of glucose catabolism (fig. 13.2). The other three components of respiratory metabolism are the tricarboxylic acid (TCA) cycle, which is responsible for further oxidation of pyruvate, the electron-transport chain, which is required for the reoxidation of coenzyme molecules at the expense of molecular oxygen, and the oxidative phosphorylation of ADP to ATP, which is driven by a proton gradient generated in the process of electron transport. Overall, this leads to the potential formation of approximately 30 molecules of ATP per molecule of glucose in the typical eukaryotic cell. 

A suspension of mitochondria is incubated with pyruvate, malate, and l4C-labeled triphenylmethyl-phosphonium [TPP] chloride under aerobic conditions. The mitochondria are rapidly collected by centrifugation, and the amount of l4C that they contain is measured. In a separate experiment, the volume of the mitochondrial matrix space was determined so that the concentration of TPP cation in the matrix can be calculated. The internal concentration is found to be 1,000 times greater than that in the external solution. 

Under aerobic conditions, the pyruvic acid is converted into acetyl CoA. This pathway also provides an NADH, along with carbon dioxide, as shown in Figure 12.40. 

Following this route under aerobic conditions, pyruvate is converted to acetyl CoA by the enzyme pyruvate dehydrogenase and the acetyl CoA then enters the citric acid cycle. The pyruvate dehydrogenase reaction is an oxidative decarboxylation (see Topic LI for details) ... 

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...

The characteristic feature of carbohydrate breakdown in cestodes is the production of a range of complex end-products, usually organic acids, even under aerobic conditions (Table 5.4). This contrasts with predominantly aerobic organisms, such as most free-living metazoa, where the end-product of glycolysis is almost exclusively lactic acid formed from pyruvic acid. Lactic acid is produced as a result of rapid muscular contraction carried out essentially under anaerobiosis and its production ensures a rapid expenditure of energy without the limitation due to the rate of diffusion of oxygen. The anaerobic phase is followed by an aerobic phase, where pyruvic acid is metabolised to acetyl-coenzyme A which is in turn oxidised completely to... 

The major end-products of carbohydrate metabolism in this species are lactate and succinate. The relative amount formed of each depends on the presence or absence of oxygen in the incubation medium, the presence or absence of glucose, and the presence or absence of fumarate. For example, anaerobiosis leads to an increase in lactate production, which is accompanied by a fall in the intracellular level of malate. Malate is an inhibitor of pyruvate kinase in M. expansa, so the fall in malate levels results in an increase in pyruvate kinase activity leading to a rise in lactate production. Conversely, under aerobic conditions, malate levels increase, pyruvate kinase activity is inhibited and lactate production is decreased (Fig. 5.5). 

Fig. 5.5. Proposed pathways of metabolism in Moniezia expansa scoleces under aerobic conditions cytosolic reactions. (After Bryant Behm, 1976.) OAA, oxaloacetate PYR, pyruvate, MAL, malate, LACT, lactate for other abbreviations, see the text.

When grown under aerobic conditions, the yeast produces two ATP molecules from one molecule of glucose by substrate-level phosphorylation in glycolysis. The two molecules of pyruvate produced can then be completely oxidized to CO2, and each yields a further 15 molecules of ATP. This leads to a slow decrease in the concentration of glucose, a steady production of CO2, and relatively little change in the amount of ATP. Also, the two molecules of NADH can be reoxidized to NAD+ by the electron-transport system. (This produces yet more ATP, as discussed in Chap. 14.)... 

Under aerobic conditions the TCA cycle allows for the complete oxidation of pyruvate, generating CO2 as a waste product (which we exhale). Although some ATP is generated directly in the TCA cycle, the most important product is NADH NADH is subsequently oxidised by the mitochondrial electron transfer chain, which, through oxidative phosphorylation, is the major provider of the cell s ATP requirement. 

Figure 14.1. Glucose Metabolism. Glucose is metabolized to pyruvate in 10 linked reactions. Under anaerobic conditions, pyruvate is metabolized to lactate and, under aerobic conditions, to acetyl CoA. The glucose-derived carbons are subsequently oxidized to CO2.

The first metabolic pathway that we encounter is glycolysis, an ancient pathway employed by a host of organisms. Glycolysis is the sequence of reactions that metabolizes one molecule of glucose to two molecules ofpyruvate with the concomitant net production of two molecules of ATP. This process is anaerobic (i.e., it does not require O2) inasmuch as it evolved before the accumulation of substantial amounts of oxygen in the atmosphere. Pyruvate can be further processed anaerobically (fermented) to lactate (lactic acidfermentation) or ethanol (alcoholic fermentation). Under aerobic conditions, pyruvate can be completely oxidized to CO2, generating much more ATP, as will be discussed in Chapters 17 and 18. 

Under aerobic conditions, the pyruvate generated from glucose is oxidatively decarboxylated to form acetyl CoA. In eukaryotes, the reactions of the citric acid cycle take place inside mitochondria, in contrast with those of glycolysis, which take place in the cytosol (Figure 171). 

The formation of acetyl CoA from carbohydrates is less direct than from fat. Recall that carbohydrates, most notably glucose, are processed by glycolysis into pyruvate (Chapter 16). Under anaerobic conditions, the pyruvate is converted into lactic acid or ethanol, depending on the organism. Under aerobic conditions, the pyruvate is transported into mitochondria in exchange for OH by the pyruvate carrier, an antiporter (Section 13.4). In the mitochondrial matrix, pyruvate is oxidatively decarboxylated by the pyruvate dehydrogenase complex to form acetyl CoA. 

Recall that molecular oxygen does not participate directly in the citric acid cycle. However, the cycle operates only under aerobic conditions because NAD+ and FAD can be regenerated in the mitochondrion only by the transfer of electrons to molecular oxygen. Glycolysis has both an aerobic and an anaerobic mode, whereas the citric acid cycle is strictly aerobic. Glycolysis can proceed under anaerobic conditions because NAD+ is regenerated in the conversion of pyruvate into lactate. 

---