Pyruvate in glycolysis

Thus, reversal of the glycolytic step from PEP to pyruvate requires two reactions in gluconeogenesis, pyruvate to oxaloacetate by pyruvate carboxylase and oxaloacetate to PEP by PEP carboxykinase. Given that the conversion of PEP to pyruvate in glycolysis synthesizes ATP, it is not surprising that the overall reversal of this step needs the input of a substantial amount of energy, one ATP for the pyruvate carboxylase step and one GTP for the PEP carboxy kinase step. 

What are the possible fates of pyruvate in glycolysis In glycolysis, one molecule of glucose gives rise, after a long series of reactions, to two molecules of pyruvate. Along the way, two net molecules of ATP and NADH are produced. In aerobic metabolism, pyruvate is further oxidized to carbon dioxide and water. In anaerobic metabolism, the product is lactate or, in organisms capable of alcoholic fermentation, it is ethanol. 

As glucose is oxidized to pyruvate in glycolysis, NAD is reduced to NADH. The need for a continuous supply of NAD for glycolysis is a key to understanding the fates of pyruvate. 

Describe the conversion of glucose to pyruvate in glycolysis and the subsequent conversion of pyruvate to acetyl-CoA or lactate. 

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. 

The next steps of glucose catabolism are called the citric acid cycle. The pyruvic acid formed in glycolysis is transported into the mitochondria, which arc subcellular organelles with double (inner and outer) membranes. They are referred to as the powerhous-... 

ATP from the 2 NTVDH produced in glycolysis (I NADH per pyruvic acid),... 

Let us consider Figure 5.3 again. Both pyruvate kinase and dtrate synthase (enzymes III and V) are inhibited by elevated ATP concentrations. During citric acid production ATP concentrations are likely to arise (ATP produced in glycolysis) and either of these enzymes could, if inhibited, slow down the process. In fact all of the evidence suggests that both enzymes are modified or controlled in some way such that they are insensitive to other cellular metabolites during citric add production. 

Start with the easy ones Glucose [compound (iv) ] should be familiar to you and it is one of only two substrates in glycolysis which is not phosphorylated the other one being pyruvate [compound (i)]. 

Examples of substrate level phosphorylation are to be found in glycolysis. Phos-phoglycerate kinase (PGK) and pyruvate kinase (PK) catalyse the following reactions ... 

Feed-forward control is more likely to be focused on a reaction occurring at or near the end of a pathway. Compounds produced early in the pathway act to enhance the activity of the control enzyme and so prevent a back log of accumulated intermediates just before the control point. An example of feed-forward control is the action of glucose-6-phosphate, fructose-1,6-bisphosphate (F-l,6bisP) and phosphoenol pyruvate (PEP), all of which activate the enzyme pyruvate kinase in glycolysis in the liver. 

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