Pyruvate from glycolysis

In 1937 Krebs found that citrate could be formed in muscle suspensions if oxaloacetate and either pyruvate or acetate were added. He saw that he now had a cycle, not a simple pathway, and that addition of any of the intermediates could generate all of the others. The existence of a cycle, together with the entry of pyruvate into the cycle in the synthesis of citrate, provided a clear explanation for the accelerating properties of succinate, fumarate, and malate. If all these intermediates led to oxaloacetate, which combined with pyruvate from glycolysis, they could stimulate the oxidation of many substances besides themselves. (Kreb s conceptual leap to a cycle was not his first. Together with medical student Kurt Henseleit, he had already elucidated the details of the urea cycle in 1932.) The complete tricarboxylic acid (Krebs) cycle, as it is now understood, is shown in Figure 20.4. 

Pyruvate derived from glycolysis or from catabolism of certain amino acids is transported from the cytoplasm into the mitochondrial matrix. 

We saw in Chapter 14 that the energy yield from the production of two molecules of pyruvate from one molecule of glucose in glycolysis is 2 ATP and 2 NADH. In oxidative phosphorylation (Chapter 19), passage of two electrons from NADH to 02 drives the formation of about 2.5 ATP, and passage of two electrons from FADH2 to 02 yields about 1.5 ATP. This stoichiometry allows us to calculate the overall yield of ATP from the complete... 

Now let us consider the further conversion of PEP and of the triose phosphates to glucose 1-phosphate, the key intermediate in biosynthesis of other sugars and polysaccharides. The conversion of PEP to glucose 1-P represents a reversal of part of the glycolysis sequence. It is convenient to discuss this along with gluconeogenesis, the reversal of the complete glycolysis sequence from lactic acid. This is an essential part of the Cori cycle (Section F) in our own bodies, and the same process may be used to convert pyruvate derived from deamination of alanine or serine (Chapter 24) into carbohydrates. 

The beauty of the metabolic cycle through pyruvate, shown in summary in Figure 20-11, is the way it can be tapped at various points according to whether the organism requires ATP (from glycolysis), NADH (from pentose shunt), or NAD (from the lactate siding). 

Pyruvate, from glycolysis of glucose, is carboxylated to oxaloacetate or oxidized to acetyl-CoA. These metabolites enter the Krebs cycle, are metabolized to a-ketoglutarate and oxaloacetate, then transaminated to aspartate or glutamate. Asn, Gin, and Pro are synthesized from Asp or Glu. The cycle replenishes intermediates via the anaplerotic reactions (e.g., car-boxylation of pyruvate to form oxaloacetate). 

Today the metabolic network of the central metabolism of C. glutamicum involving glycolysis, pentose phosphate pathway (PPP), TCA cycle as well as anaplerotic and gluconeogenetic reactions is well known (Fig. 1). Different enzymes are involved in the interconversion of carbon between TCA cycle (malate/oxaloacetate) and glycolysis (pyruvate/phosphoenolpyruvate). For anaplerotic replenishment of the TCA cycle, C. glutamicum exhibits pyruvate carboxylase [20] and phosphoenol-pyruvate (PEP) carboxylase as carboxylating enzymes. Malic enzyme [21] and PEP carboxykinase [22,23] catalyze decarboxylation reactions from the TCA cycle... 

Why is a carboxylation and a decarboxylation required to form phos-phoenol pyruvate from pyruvate Recall that, in glycolysis, the presence of a... 

In contrast to gluconeogenesis, the formation ol pyruvate from phosphoenolpyruvate during glycolysis requires only pyruvate kinase, and ATP is made. 

Synthesis of pyruvate. In the final reaction of glycolysis, pyruvate kinase catalyzes the transfer of a phosphoryl group from PEP to ADP. Two molecules of ATP are formed for each molecule of glucose. 

The pathway involved is glycolysis, the conversion of glucose to pyruvate. The initial step is phosphorylation of glucose by the enzyme hexokinase and the final step is formation of pyruvate from phosphoenolpyruvate by pyruvate kinase (Chapter 11). The BPG is made from an intermediate compound, 1,3-bisphosphoglycerate, by the enzyme bisphosphoglycerate mutase. 

For the acetyl CoA produced by the p-oxidation of fatty acids to efficiently enter the citric acid cycle, there must be an adequate supply of oxaloacetate. If glycolysis and p-oxidation are occurring at the same rate, there will be a steady supply of pyruvate (from glycolysis) that can be converted to oxaloacetate. But what happens if the supply of oxaloacetate is too low to allow all of the acetyl CoA to enter the citric acid cycle Under these conditions, acetyl CoA is converted to the so-called ketone bodies p-hydroxybut)rrate, acetone, and acetoacetate (Figure 23.9). 

The function of acetyl CoA in the citric acid cycle is to bring the two-carbon remnant (acetyl group) of pyruvate from glycolysis and transfer it to oxaloacetate. In this way the acetyl group enters the citric acid cycle for the final stages of oxidation. 

Glutamate donates its amine group to pyruvate (from glycolysis) to form alanine and a-ketoglutarate. 

In fact the word glycolysis comes from two Greek words that mean "splitting sugars" (glykos, "sweet," and lysis, "to split"). In this pathway, the six-carbon sugar glucose is spli and then oxidized, to produce two three-carbon molecules, called pyruvate. 

As glucose is being oxidized to CO2, it is first oxidized to pyruvate in the pathway of glycolysis. Pyruvate is then oxidized to acetyl CoA. The acetyl group enters the tricarboxylic acid (TCA) cycle, where it is completely oxidized to CO2. Energy from the oxidative reactions is used to generate ATP. 

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. 

Recall How does pyruvate from glycolysis get to the pyruvate dehydrogenase complex ... 

Entry of 2-carbon units is carried out by pyruvate dehydrogenase and citrate synthase in the first phase of the TCA cycle. Pyruvate from glycolysis or other pathways enters the TCA cycle through the action... 

Glycolysis produces two molecules of pyruvate from one molecule of glucose, which when fed into the Krebs cycle give six molecules of CO2 according to the overall equation... 

A variety of monosaccharides (hexoses or pentoses) can be fermented to produce 2,3-BD (Syu, 2001). In bacterial metabolism, monosaccharides must first be converted to pyruvate before generation of major products. From glucose, pyruvate is formed in a relatively simple manner via the Embden-Meyerhof pathway (glycolysis). In contrast, the production of pyruvate from pentoses must proceed via a combination of the pentose phosphate and Embden-Meyerhof pathways (Jansen and Tsao, 1983). In addition to 2,3-BD, the pyruvate produced from the monosaccharides is then channeled into a mixture of acetate, lactate, formate, succinate, acetoin, and ethanol, through the mixed acid-2,3-BD fermentation pathway (Ji et al., 2011a). 

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