Krebs cycle overall reaction

What is the overall reaction mediated by the Krebs cycle What does it produce that the body needs ... 

The urea cycle Urea is synthesized in the liver by the urea cycle. It is then secreted into the bloodstream and taken up by the kidneys for excretion in the urine. The urea cycle was the first cyclic metabolic pathway to be discovered by Hans Krebs and Kurt Henseleit in 1932,5 years before Krebs discovered the citric acid cycle (see Topic LI). The overall reaction of the pathway is ... 

Acetyl-CoA is oxidized to C02 by the Krebs cycle, also called the tricarboxylic acid cycle or citric acid cycle. The origin of the acetyl-CoA may be pyruvate, fatty acids, amino acids, or the ketone bodies. The Krebs cycle may be considered the terminal oxidative pathway for all foodstuffs. It operates in the mitochondria, its enzymes being located in their matrices. Succinate dehydrogenase is located on the inner mitochondrial membrane and is part of the oxidative phosphorylation enzyme system as well (Chapter 17). The chemical reactions involved are summarized in Figure 18.7. The overall reaction from pyruvate can be represented by Equation (18.5) ... 

Enzymes involved in the /3-oxidation pathway are located on the inner side of the inner mitochondrial membrane or in the peroxisomes. The design of this pathway involves the oxidative and stepwise removal of acetyl-CoA units from the shrinking fatty acid chain, the acetyl-CoA molecules being fed into the Krebs cycle (Chapter 18) or forming ketone bodies (see later). The overall reaction, involving palmitic acid, may be represented by Equation (19.7) ... 

The Krebs cycle is a series of reactions catalyzed by sev en enzymes in mitochondria. Its function is to catalyze removal of electrons from nutrients and to transfer them to NAD and FAD, producing NADH plus H, and FADHj, respectively. These reduced cofactors exist only momentarily in their reduced (err oxidized) forms as they continually accept and then donate electrons to the respiratory chain. The respiratory chain, composed of a number of cytochromes, uses electrons for reduction of to water, This reduction process is accompanied by or coupled with the regeneration of ATP, that is, conversion of A DP back to ATE The overall effect may be summarized thus The Krebs cycle and respiratory chain arc used for oxidizing nutrients io COy and for the production of energy. 

The initial stages of catabolism result in the conversion of both fats and carbohydrates into acetyl groups that are bonded through a thioester link to coenzyme A. Acetyl CoA then enters the next stage of catabolism—the citric acid cycle, also called the tricarboxylic acid (TCA) cycle, or Krebs cycle, after Hans Krebs, who unraveled its complexities in 1937. T he overall result of the cycle is the conversion of an acetyl group into two molecules of CO2 plus reduced coenzymes by the eight-step sequence of reactions shown in Figure 29.12. 

Figure 14-1. The tricarboxylic acid (TCA) cycle, also known as the citric acid cycle and the Krebs cycle. The overall reaction is...

As for human cells or enkaryotes, the metabolic path or seqnence involves the conversion of glucose by what is labeled glycolysis. In a series of ten steps there is first produced a compound called pyruvic acid or pyruvate (the latter designating a so-called salt or componnd of pyruvic acid). In the presence of oxygen, this is fnrther converted to carbon dioxide and water in what is variously called the tricarboxylic acid cycle, or citric acid cycle, or Krebs cycle. The overall operation may be conveniently called aerobic glycolysis, with each step requiring a particnlar enzyme, and most usually requiring snpportive reactions. 

The Krebs cycle is central to nearly all cellular metabolism, and its history may date prior to the first cells or even before the first enzymes (Trefil et al., 2009). These metabolic reactions result in products with overall energy levels less than those of the reactants. In cells that derive their energy from oxidation of carbon-based molecules, the Krebs cycle results in high-energy electrons that power the cells through ATP formation and use. For certain primitive cells that derive their energy from chemical sources, the Krebs cycle can run... 

As pyruvic acid decarboxylation constitutes the link between glycolysis and the Krebs cycle, a-ketoglutaric decarboxylation divides the reactions involving 6-carbon acids (citrate, isocitrate, and oxalosuccinate) and those involving 4-carbon acids (succinate, fumarate, and malate). The analogy between the two reactions is not restricted to their role in intermediate metabolism, but extends also to the mechanism of action of the two multiple-enzyme systems. In a-ketoglutaric decarboxylation, the overall reaction leads to the formation of CO2 and succinate. CoA, NAD, thiamine, lipoic acid, and magnesium are requirements for this multiple-enzyme system activity. 

Various relationships between enzymes of the Krebs cycle and mitochondria are possible. For instance, all enzymes could be enclosed within mitochondrial structures or the enzymes could take part in the structural build-up of the cell. There is no evidence demonstrating that all enzymes of the Krebs cycle are part of the mitochondria. The existence of enzymes with multiple catalytic properties (isocitric dehydrogenase, aconitase, and malic dehydrogenase) and the failure to separate the multiple steps of an overall reaction (pyruvic and a-ketoglutarate oxidation) are sometimes taken as evidence for the participation of the enzyme in the building-up of the mitochondrial structure, but these arguments do not take into account the limitations of the actual biochemical methods, and, therefore, conclusions based upon them are premature. 

When in later years Krebs reviewed the major points which had to be established if the cycle was to be shown to be operative in cells, the obvious needs were to find the presence of the required enzymes and to detect their substrates. As the substrates are present in the cycle in catalytic amounts their accumulation required the use of inhibitors. Krebs also stressed that rates of oxidation of the individual substrates must be at least as fast as the established rates of oxygen uptake in vivo, an argument first used by Slator (1907) with reference to fermentation A postulated intermediate must be fermented at least as rapidly as glucose is. (See Holmes, 1991). This requirement did not always appear to be met. In the early 1950s there were reports that acetate was oxidized by fresh yeast appreciably more slowly than the overall rate of yeast respiration. It was soon observed that if acetone-dried or freeze-dried yeasts were used in place of fresh yeast, rates of acetate oxidation were increased more than enough to meet the criterion. Acetate could not penetrate fresh yeast cell walls sufficiently rapidly to maintain maximum rates of respiration. If the cell walls were disrupted by drying this limitation was overcome, i.e. if rates of reaction are to be... 

Note that because all catalysts (oxaloacetate, enzymes etc.) must be regenerated in looking at the overall operation of the cycle, only the acetyl group of acetyl-CoA can be oxidized completely. Some intermediates, such as citrate, can be partially oxidized, but Kreb s cycle intermediate catabolism requires leaving the cycle at oxaloacetate and then returning as acetyl-CoA. It requires leaving the mitochondria for some reactions, and since the extremely low concentrations of oxaloacetate don t allow its efficient transport across the mitochondrial membrane (the Km of the carrier is much higher than [oxaloacetate]), malate is the species which actually leaves the mitochondria. 

Under aerobic conditions, the main metabolic route is oxidation to carbon dioxide and water (respiration). In order to accomplish this, the pyruvic acid from the glycolysis process enters another series of reactions known as the Krebs Tricarboxylic Acid cycle (Citric Acid cycle) (Figure 11.21), where overall breakdown occurs with elimination of CO2 and H2O [9]. 

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