Glycolytic cycle

Example 13.11 Enzymatic reactions Oscillations in the glycolytic cycle Biochemical chains are highly likely to exhibit limit cycles and dissipative structures. Oscillations appear in living systems in a variety of ways with... 

The enzyme phosphofructokinase is allosteric, that is, it is made up of equivalent units that possess specific reaction sites for the fixation of the substrate and product. Each unit exists in two conformational states one active with more affinity for the substrate, and one inactive. The reaction products of phosphofructokinase (FDP and ADP) displace the conformational equilibrium in favor of the active form of the enzyme. This may create a destabilizing effect on the excess entropy production. In the glycolytic cycle, the allosteric properties of the phosphofructokinase may lead to oscillations. Consider the following simple model... 

When sodium fluoride is used alone for anticoagulation, three to five times greater concentrations than the usual 2 g/L are required. This high concentration and the inhibition of the glycolytic cycle are likely to cause fluid shifts and a change in the concentration of some analytes. Fluoride is also a potent inhibitor of many serum enzymes and in high concentrations also affects urease, used to measure urea nitrogen in many analytical systems. 

As noted above, however, NAD must be regenerated from the NADH produced or the glycolytic cycle would cease. Under aerobic conditions regeneration of cytosohc NAD+ from cytosolic NADH is accomplished by transferring electrons across the mitochondrial membrane barrier to the electron transfer chain where the electrons are transferred to oxygen. There are two different shuttle mechanisms whereby this transfer of electrons across the membrane to regenerate cytosohc NAD+ can be accomplished, the glycerol 3-phosphate shuttle and the malate-aspartate shuttle. 

The effect of vitamin D deficiency upon plasma calcium is not primarily due to malabsorption of calcium from the gastrointestinal tract. In addition to its well-known effect on calcium absorption, vitamin D contributes directly to the maintenance of plasma calcium by the skeleton by a direct action on bone similar to that of parathyroid hormone (C2, C16). The vitamin D effect may be mediated by an action on the Krebs glycolytic cycle, resulting in inhibition of citrate oxidation (S6). 

Example 13.12 Enzymatic reactions—Oscillations in the glycolytic cycle... 

Glucose is not the only hexose used for glycolysis— fructose, mannose, and galactose can also enter the glycolytic cycle after phosphorylation. Like glucose, fructose can be used only after phosphorylation in one of three ways [33] (1) phosphorylation to fructose-6-phosphate by hexokinase, (2) phosphorylation to fructose-6-phosphate by a specific fructokinase, and (3) phosphorylation to fructose-1-phosphate by fructokinase (Fig. 1-7). It is well established that the glu-cokinase of liver and muscle can also phosphorylate fructose. Fructose can enter muscle metabolism only in the form of fructose-6-phosphate. This is strikingly different from liver metabolism in which fructose is converted to fructose-1-phosphate by a specific fructokinase. 

The fate of fructose-1-phosphate is varied—it may be phosphorylated again in the presence of 1-phospho-fructokinase, magnesium, and ATP to yield fructose-1,6-diphosphate and ADP. 1-Phosphofructokinase is found in liver and muscle. Fructose-1,6-diphosphate may then be used by the glycolytic cycle. 

The observations made in vitro have shed some light on numerous problems related to the mode of action of insulin and the pathogenesis of diabetes. Among such problems are the primary site of action of insulin, the intracellular localization of the glycolytic cycle, and the pathway of glycogen synthesis in muscle. 

ATP Synthesis. Inasmuch as the first steps in glucose metabolism start with the phosphorylation of hexoses in the presence of ATP, a direct effect of insulin on the formation of the high-energy phosphates could explain the effect of the hormone on glucose utilization, and an impairment of the rate of ATP synthesis could be responsible for the biochemical lesions of diabetes. Without ATP, glucose cannot enter the glycolytic cycle. Insulin could affect phosphorus metab-... 

Biochemical systems are also often reaction cycles where the key catalytic intermediate is generated, consumed, and subsequently regenerated as the part of the complex reaction cycle. Enzymes catalyze the formation of the intermediates that participate in the overall reaction cycle. These are intricately catalyzed reaction systems where the intermediates that form subsequently act as catalysts. The citric acid cycle, which was discussed in Section 2.1 (see also Fig. 2.5), is one such cycle. Two other complex reaction systems comprised of many catalytic steps that are of key metabolic importance are the Calvin and glycolytic cycles. 

Adenosine serves as a carbon source for mammalian cells by its deamination to inosine in the presence of ADA, the cleavage of inosine to hypoxanthine and ribose-l-P in the presence of purine nucleoside phosphorylase, the conversion of ribose-l-P to ribose-5-P in the presence of phosphopentomutase and then the entrance of ribose-5-P into the glycolytic cycle. To insure that adenosine utilization is mediated by ADA and to avoid the inhibitory effects of adenosine on cell growth, a tubercidin resistant mutant (tub ) deficient in adenosine kinase activity was selected initially. 

We plan to make a systematic survey of all substances in the biological cycles (such as the Krebs and glycolytic cycles) whose structures indicate that they have coordinating ability. Almost every compound in the Krebs cycle is a possibility. The objectives of further investigation will be to ascertain the composition of the more promising complexes, to determine their relative biological effects, and to relate biological activity to structure. 

Galactose can enter the glycolytic cycle but it must first react with ATP to form galactose-1-phosphate. Propose a mechanism for... 

Example 13.11 Enzymatic reactions Oscillations in the glycolytic cycle Biochemical chains are highly likely... 

The eleven constituent enzymes of the glycolytic system fall into the following categories dehydrogenases (2) phosphokinases (4) isomerases (4) and aldolase (1). The ratio of the number of dehydrogenases to the total number of enzymes is 2 11 in the glycolytic cycle and 5 12 in the citric-acid cycle. 

There exists in animal and plant tissues, as well as in some bacteria, a system of enzymes which oxidatively converts glucose to tetrosephos-phate, triosephosphate, and C02 by reactions other than those involved in the Embden-Meyerhof glycolytic cycle. Warburg, Dickens, Horecker, S. S. Cohen,Dische, and Racker have made important contributions to our knowledge of this reaction sequence, which appears to provide the starting materials for the synthesis of ribose, deoxyribose, and their corresponding nucleotides. For ease of presentation the reactions may be subdivided as follows ... 

In the glycolytic cycle there are three important systems responsible for the synthesis of bonds (1) the oxidation of phosphoglyceraldehyde to phosphoglyceric acid (2) the dehydration of phosphoglyceric acid to phosphoenolpyruvic acid and (3) the transfer of electrons from reduced DPN aerobically to oxygen. 

For over three decades the enzymes of the glycolytic cycle have been the subject of Augorous research by many investigators. Since much has been written concerning the details of the glycolytic reactions, this section... 

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