Citric acid cycle oxaloacetate regeneration

Reactions of four-carbon compounds constitute the final stage of the citric acid cycle the regeneration of oxaloacetate. 

As its name implies, the citric acid cycle is a closed loop of reactions in which the product of the hnal step (oxaloacetate) is a reactant in the first step. The intermediates are constantly regenerated and flow continuously through the cycle, which operates as long as the oxidizing coenzymes NAD+ and FAD are available. To meet this condition, the reduced coenzymes NADH and FADH2 must be reoxidized via the electron-transport chain, which in turn relies on oxygen as the ultimate electron acceptor. Thus, the cycle is dependent on the availability of oxygen and on the operation of the electron-transport chain. 

The citric acid cycle is the final pathway for the oxidation of carbohydrate, Upid, and protein whose common end-metabolite, acetyl-CoA, reacts with oxaloacetate to form citrate. By a series of dehydrogenations and decarboxylations, citrate is degraded, releasing reduced coenzymes and 2CO2 and regenerating oxaloacetate. 

Formation of citrulline Ornithine and citrulline are basic amino acids that participate in the urea cycle. [Note They are not incorporated into cellular proteins, because there are no codons for these amino acids (see p. 429).] Ornithine is regenerated with each turn of the urea cycle, much in the same way that oxaloacetate is regenerated by the reactions of the citric acid cycle (see p 109). The release of the high-energy phosphateof carbamoyl phosphate as inorganic phosphate drives the reaction in the forward direction. The reaction product, citrulline, is trans ported to the cytosol. 

Although oxaloacetate is regenerated and therefore not consumed during the operation of the citric acid cycle, it also enters other metabolic pathways. 

The primary substrate of the citric acid cycle is acetyl-CoA. Despite many references in the biochemical literature to substrates "entering" the cycle as oxaloacetate (or as one of the immediate precursors succinate, fumarate, or malate), these compounds are not consumed by the cycle but are completely regenerated hence the term regenerating substrate, which can be applied to any of these four substances. A prerequisite for the operation of a catalytic cycle is that a regenerating substrate be readily available and that its concentration... 

Answer Oxygen consumption is a measure of the activity of the first two stages of cellular respiration glycolysis and the citric acid cycle. Initial nutrients being oxidized are carbohydrates and lipids. Because several intermediates of the citric acid cycle can be siphoned off into biosynthetic pathways, the cycle may slow down for lack of oxaloacetate in the citrate synthase reaction, and acetyl-CoA will accumulate. Addition of oxaloacetate or malate (converted to oxaloacetate by malate dehydrogenase) will stimulate the cycle and allow it to use the accumulated acetyl-CoA. This stimulates respiration. Oxaloacetate is regenerated in the cycle, so addition of oxaloacetate (or malate) stimulates the oxidation of a much larger amount of acetyl-CoA. 

Formation of Oxaloacetate in a Mitochondrion In the last reaction of the citric acid cycle, malate is dehydrogenated to regenerate the oxaloacetate necessary for the entry of acetyl-CoA into the cycle ... 

Answer In the citric acid cycle, the entering acetyl-CoA combines with oxaloacetate to form citrate. One turn of the cycle regenerates oxaloacetate and produces two C02 molecules. There is no net synthesis of oxaloacetate in the cycle. If any cycle intermediates are channeled into biosynthetic reactions, replenishment of oxaloacetate is essential. Four enzymes can... 

With the regeneration of oxaloacetate in step 8, the cycle of reactions is completed, and the oxaloacetate condenses with another molecule of acetyl-CoA to commence another turn of the cycle. However, note that there is actually no beginning or end to the citric acid cycle (Fig. 12-2) if any of the intermediates are produced within the mitochondria or gain access to the mitochondria, they can participate in the cycle of reactions but they will always be regenerated. The only actual fuel for the cycle is acetyl-CoA and this is not regenerated its carbon atoms are liberated at steps 3 and 4 as C02. 

STEPS 7-8 Regeneration of oxaloacetate. Catalyzed by the enzyme fumarase. conjugate miclcophilic addition of w ater to fumarate yields t-malate in a reaction simUar to tliat of step 2 in the fatty acid j3>oxidation pathway. Oxida-i m with NAD then, gives oxaloacetate in a step catalyzed by malate dehydrogenase, and the citric acid cycle has return to ita starting point, ready to revolve again. 

This series of reactions completes the Calvin cycle (Figure 20.12). The sum of all the reactions results in the generation of a hexose and the regeneration of the starting compound, ribulose 5-phosphate. In essence, ribulose 1,5-bisphosphate acts catalytically, similarly to oxaloacetate in the citric acid cycle. 

It is important to note that animals are unable to effect the net synthesis of glucose from fatty acids. Specifically, acetyl CoA cannot be converted into pyruvate or oxaloacetate in animals. The two carbon atoms of the acetyl group of acetyl CoA enter the citric acid cycle, but two carbon atoms leave the cycle in the decarboxylations catalyzed by isocitrate dehydrogenase and a-ketoglutarate dehydrogenase. Consequently, oxaloacetate is regenerated, but it is not formed de novo when the acetyl unit of acetyl CoA is oxidized by the citric acid cycle. In contrast, plants have two additional enzymes enabling them to convert the carbon atoms of acetyl CoA into oxaloacetate (Section 17.4.). 

The overall pattern of the citric acid cycle is shown in Figure 17.2. A four-carbon compound (oxaloacetate) condenses with a two-carbon acetyl unit to yield a six-carbon tricarboxylic acid. The six-carbon compound releases CO2 twice in two successive oxidative decarboxylations that yield high-energy electrons. A four-carbon compound remains. "This four-carbon compound is further processed to regenerate oxaloacetate, which can initiate another round of the cycle. Two carbon atoms enter the cycle as an acetyl unit and two carbon atoms leave the cycle in the form of two molecules of CO . 

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