Malate glucose oxidation

Because the 2 NADH formed in glycolysis are transported by the glycerol phosphate shuttle in this case, they each yield only 1.5 ATP, as already described. On the other hand, if these 2 NADH take part in the malate-aspartate shuttle, each yields 2.5 ATP, giving a total (in this case) of 32 ATP formed per glucose oxidized. Most of the ATP—26 out of 30 or 28 out of 32—is produced by oxidative phosphorylation only 4 ATP molecules result from direct synthesis during glycolysis and the TCA cycle. 

NADPH is produced during the transfer of acetyl groups from the mitochondrion, when malate is oxidized to pyruvate and carbon dioxide [see Fig. 13-8 and reaction (c) in the accompanying text], NADPH is also produced when glucose is oxidized and decarboxylated to ribulose 5-phosphate (Chap. 11). 

Note The current value of 30 molecules of ATP per molecule of glucose supersedes the earlier one of 36 molecules of ATP. The stoichiometries of proton pumping, ATP synthesis, and metabolite transport should be regarded as estimates. About two more molecules of ATP are formed per molecule of glucose oxidized when the malate-aspartate shuttle rather than the glycerol 3-phosphate shuttle is used. 

Thus, citrate not only modulates the rate of fatty acid synthesis but also provides carbon atoms for the synthesis. The oxaloacetate formed from pyruvate may eventually be converted (via malate) to glucose by the gluconeogenic pathway. The glucose oxidized via the pentose phosphate pathway augments fatty acid synthesis by providing NADPH. Pyruvate generated from oxaloacetate can enter mitochondria and be converted to oxaloacetate, which is required for the formation of citrate. 

I was able to obtain malate oxidation either in dialyzed yet concentrated kidney cortex extracts or by a very reproducible technique with kidney brei washed 3 to 4 times with distilled water and then extracted with phosphate. The phosphate extract was incubated with malate in the presence of fluoride. Glucose was not added. Malate underwent oxidation and phosphopyruvate accumulated.< > >... 

Succinyl-CoA derived from propionyl-CoA can enter the TCA cycle. Oxidation of succinate to oxaloacetate provides a substrate for glucose synthesis. Thus, although the acetate units produced in /3-oxidation cannot be utilized in glu-coneogenesis by animals, the occasional propionate produced from oxidation of odd-carbon fatty acids can be used for sugar synthesis. Alternatively, succinate introduced to the TCA cycle from odd-carbon fatty acid oxidation may be oxidized to COg. However, all of the 4-carbon intermediates in the TCA cycle are regenerated in the cycle and thus should be viewed as catalytic species. Net consumption of succinyl-CoA thus does not occur directly in the TCA cycle. Rather, the succinyl-CoA generated from /3-oxidation of odd-carbon fatty acids must be converted to pyruvate and then to acetyl-CoA (which is completely oxidized in the TCA cycle). To follow this latter route, succinyl-CoA entering the TCA cycle must be first converted to malate in the usual way, and then transported from the mitochondrial matrix to the cytosol, where it is oxida-... 

Notice that none of the intermediates of the citric add cyde appear in this reaction, not as reactants or as products. This emphasizes an important (and frequently misunderstood) point about the cycle. It does not represent a pathway for the net conversion of acetyl CoA to citrate, to malate, or to any other intermediate of the cyde. The only fate of acetyl CoA in this pathway is its oxidation to CO,. Therefore, the dtric acid cycle does not represent a pathway by which there can be net synthesis of glucose from acetyl CoA... 

NADPH is required for many biosynthetic sequences. It is generated in different kinds of cells by a variety of reactions, including an NADP+-linked oxidation of malate to pyruvate and C02 and transfer of hydride ion from NADH to NADP+ in a mitochondrial reaction that is driven by metabolic energy. However, in many cases, including in the mammalian liver, a major part of the NADPH requirement is met by oxidation of glucose-6-phosphate to ribulose-5-phosphate and C02. The four electrons that are released by the oxidation are transferred to two molecules of NADP+. 

The fumarate released in the urea cycle links the urea cycle with the TCA cycle. This fumarate is hydrated to malate, which is oxidized to oxaloacetate. The carbons of oxaloacetate can stay in the TCA cycle by condensation with acetyl-CoA to form citrate, or they can leave the TCA cycle either by gluconeogenesis to form glucose or by transamination to form aspartate as shown in figure 22.9. Because Krebs was involved in the discoveries of both the urea cycle and the TCA cycle, the interaction between the two cycles shown in figure 22.9 is sometimes referred to as the Krebs bicycle. 

This transfer of reducing equivalents is essential for maintaining the favorable NAD+/NADH ratio required for the oxidative metabolism of glucose and synthesis of glutamate in brain (McKenna et al., 2006). The malate-aspartate shuttle is considered the most important shuttle in brain. It is particularly important in neurons. It has low activity in astrocytes. This shuttle system is fully reversible and linked to amino acid metabolism with the energy charge and citric acid cycle of neuronal cells. 

Oxidation of reduced pyridine nucleotides Reaction with isocitrate dehydrogenase, glucose 6-phosphate dehydrogenase, malate dehydrogenase Reaction with GSH... 

Answer NADH produced in the cytosol cannot cross the inner mitochondrial membrane, but must be oxidized if glycolysis is to continue. Reducing equivalents from NADH enter the mitochondrion by way of the malate-aspartate shuttle. NADH reduces oxaloacetate to form malate and NAD+, and the malate is transported into the mitochondrion. Cytosolic oxidation of glucose can continue, and the malate is converted back to oxaloacetate and NADH in the mitochondrion (see Fig. 19-29). 

In starvation, glucose making, stimulating PEP CK Uses oxaloacetic, also lost another way Ketone bodies, what is odd is that the oxidation state Also favours the reduction of OA to give malate. 

Pyrophosphate is rapidly hydrolyzed, and so the equivalent of four molecules of ATP are consumed in these reactions to synthesize one molecule of urea. The synthesis of fumarate by the urea cycle is important because it links the urea cycle and the citric acid cycle (Figure 23.17). Fumarate is hydrated to malate, which is in turn oxidized to oxaloacetate. Oxaloacetate has several possible fates (1) transamination to aspartate, (2) conversion into glucose by the gluconeogenic pathway, (3) condensation with acetyl CoA to form citrate, or (4) conversion into pyruvate. 

The pyruvate produced at point (3) can be used to produce energy within the liver or for gluconeogenesis. Pyruvate produces energy when it is oxidized in the mitochondria by the Krebs cycle. It is used for gluconeogenesis when it is converted in the mitochondria to OAA, then to malate, which, after exit from the mitochondria, is converted to PEP and eventually to glucose. 

Carbohydrates are introduced into the Krebs cycle at the point where pyruvate dehydrogenase catalyzes conversion of pyruvate to acetyl-Co A with the concomitant reduction of NAD. Citrate synthase catalyzes introduction of the 2-carbon unit of acetyl-CoA into the Krebs cycle. Pyruvate can arise from glucose, fructose, lactate, alanine, and glycerol. Acetyl-CcjAcan arise from pyruvate, as well as from fatty acids. Oxidation of fatty acids results in production of acetyl-Co A, which enters the Krebs cycle at the point catalyzed by citrate synthase. Breakdown of ketogenic amino adds also results in the production of acctyl-CoA, which enters the Krebs cycle at this point. Citrate and malate occur in high cor centrations in certain fruits and vegetables. These chemicals directly enter the Krebs cycle at the indicated points. 

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