Methyl group of acetyl-CoA

When these labeled oxaloacetates enter a second turn of the cycle, both of the carboxyl carbons are lost as CO2, but the methylene and carbonyl carbons survive through the second turn. Thus, the methyl carbon of a labeled acetyl-CoA survives two full turns of the cycle. In the third turn of the cycle, one-half of the carbon from the original methyl group of acetyl-CoA has become one of the carboxyl carbons of oxaloacetate and is thus lost as CO2. In the fourth turn of the cycle, further scrambling results in loss of half of the remaining labeled carbon (one-fourth of the original methyl carbon label of acetyl-CoA), and so on. 

Answer The /3-oxidation pathway includes two dehydrogenase enzymes that remove hydrogen (H-H) from the fatty acyl-CoA chain, first at a —CH2—CH2— and then at a —CH2—CH(OH)—. The net result of the two reactions is removal of one of the two hydrogens at the point of formation of the enoyl-CoA intermediate. The two other hydrogens in the methyl group of acetyl-CoA come from water. 

The anomeric carbon of glucose ends up in position 3 (methyl) of pyruvate and then in the methyl group of acetyl-CoA. From this point on, follow the starred carbon atom marked by an asterisk in Figure 18.7. 

No. Figure 12-11 shows the fate of the carbon atoms of one molecule of acetyl-CoA in two turns of the cycle. The two carbon atoms can be followed until step 5, the formation of the symmetrical molecule succinate, when they become randomized. This means that the two methylene carbons of the symmetrical molecule succinate have equal probability of arising from the methyl group of acetyl-CoA. Steps 3 and 4 of the second turn each yield C02, which represents, at each step, 50 percent of the original carboxyl carbon of acetyl-CoA. During the third turn of the cycle, these two steps collectively liberate 50 percent of the remaining labeled methyl carbon as C02, and so forth for subsequent turns of the cycle. 

In Methanosarcina and Methanothrix" CH3-C0M, an intermediate of acetoclastic methanogenesis, is formed by transfer of the methyl group of acetyl-CoA to CoM [231,237,239,242]. This conversion. 

The first reaction of the TCA cycle is catalyzed by citrate synthase and involves a carbanion formed at the methyl group of acetyl-CoA that undergoes aldol condensation with the carbonyl carbon atom of the oxaloacetate ... 

Is any reasonable mechanism consistent with the data The answer lies in an observation of a probable isotope effect in a coupled nonenzymic phenomenon. The double-isotope fractionation method does not enter into the analysis. The keto group of glyoxalate is actually present as a covalent hydrate to the extent of about 99% of the total glyoxalate concentration (27). However, the ketone is the form that will react in the enzymic process and the concentration of ketone determines the rate of reaction and binding to the enzyme. The equilibrium between ketone and hydrate is not catalyzed by the enzyme and as a result the isotope effect on this equilibrium will appear in the measured kinetic isotope effects. Of course, the extent of this equilibrium will not be affected by deutera-tion of the methyl group of acetyl-CoA. Therefore, the observed HVIK) is not an indication of kinetically significant carbon-carbon bond formation but of a preequilibrium hydration, a process that is independent of the enzyme. The value for HV/K) of 1.0037 is consistent with measured equilibrium isotope effects in related molecules (23). Therefore, the deuteration of acetyl-CoA has no effect on the observed kinetic because that value in fact is due to a preequilib-... 

The methyl group of acetyl CoA becomes the co-carbon (the terminal methyl group) of palmitate. Each new 2-carbon unit is added to the carboxyl end of the growing fatty acyl chain (see Fig. 33.13). 

The structure of cholesterol suggests that its synthesis involves multimolecular interactions yet all of the 27 carbons are derived from one precursor, acetyl CoA. Acetyl CoA can be obtained from several sources, including the beta oxidation of fatty acids, the oxidation of ketogenic amino acids, such as leucine and lysine, and the pyruvate dehydrogenase reaction. Carbons 1, 2, 5, 7, 9, 13, 15, 18, 19, 20, 22, 24, 26, and 27 of cholesterol are derived from the methyl group of acetyl CoA and the remaining 12 carbons of cholesterol from the carboxylate atom of acetyl CoA. 

A connecting point between anaerobic glycolysis and j3-oxidation is the formation of acetyl-CoA. Which carbon atoms of glucose appear as methyl groups of acetyl-CoA Which carbon atoms of palmitic acid appear as methyl groups of acetyl-CoA ... 

Problem 11.13. As shown in Scheme 11.89, if the methyl group of acetyl-CoA becomes the pw-S carbon in citrate, has the addition occurred to the re- or i-face of the carbonyl ... 

Thus, it seems that the methyl group of acetyl-CoA must be the a carbon of the original fatty acid and the P carbon of the fatty acid becomes the carbonyl carbon of myristate (Fig. 17.61). We will come back to this reaction in Chapter 19, but you should be able to appreciate both the extent and difficulty of the task that Nature faces here—How to break the a-P bond in palmitate That s no simple task, and we shall need the material in Chapter 19 to solve it. 

The search for the C, compound formed by condensation of pyruvic and oxaloacetic acids, originally postulated by Krebs, had been fruitless for more than 10 years. In 1949 Ochoa with the collaboration of Joseph Stern isolated an enzyme from heart muscle capable of synthesizing stoichiometric amounts of citric acid from ATP, acetate, CoA and oxaloacetate. First named condensing enzyme , it is now known as citrate synthetase. It was obtained by the Ochoa group in crystalline form, the first enzyme of the cycle to be crystallized. With the pure enzyme in hand, it was clear not only that the product was not a C, compound, but that other alternatives to citrate, namely, m-aconitate and isocitrate, could also be rejected. The citrate synthetase condensation takes place between the methyl group of acetyl-CoA and the keto group of oxaloacetic acid the reaction is reversible. 

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