Energy metabolism citric acid cycle

This oxygen-requiring (aerobic) metabolic process, which is also known as the Krebs cycle, is the means by which metabolic products of fats, carbohydrates, and protein are converted to water and carbon dioxide, plus energy. The citric acid cycle operates in the mitochondria of cells, where the appropriate enzymes are located. 

Physiological Role of Citric Acid. Citric acid occurs ia the terminal oxidative metabolic system of virtually all organisms. This oxidative metabohc system (Fig. 2), variously called the Krebs cycle (for its discoverer, H. A. Krebs), the tricarboxyUc acid cycle, or the citric acid cycle, is a metaboHc cycle involving the conversion of carbohydrates, fats, or proteins to carbon dioxide and water. This cycle releases energy necessary for an organism s growth, movement, luminescence, chemosynthesis, and reproduction. The cycle also provides the carbon-containing materials from which cells synthesize amino acids and fats. Many yeasts, molds, and bacteria conduct the citric acid cycle, and can be selected for thek abiUty to maximize citric acid production in the process. This is the basis for the efficient commercial fermentation processes used today to produce citric acid. 

FIGURE 18.2 The metabolic map as a set of dots and lines. The heavy dots and lines trace the central energy-releasing pathways known as glycolysis and the citric acid cycle. 

The combustion of the acetyl groups of acetyl-CoA by the citric acid cycle and oxidative phosphorylation to produce COg and HgO represents stage 3 of catabolism. The end products of the citric acid cycle, COg and HgO, are the ultimate waste products of aerobic catabolism. As we shall see in Chapter 20, the oxidation of acetyl-CoA during stage 3 metabolism generates most of the energy produced by the cell. 

Four of the B vitamins are essential in the citric acid cycle and therefore in energy-yielding metabolism (1) riboflavin, in the form of flavin adenine dinucleotide (FAD), a cofactor in the a-ketoglutarate dehydrogenase complex and in succinate dehydrogenase (2) niacin, in the form of nicotinamide adenine dinucleotide (NAD),... 

The citric acid cycle is a catabolic, energy-generating metabolic pathway that is found enormously commonly in living nature. 

Fluoroacetate produces its toxic action by inhibiting the citric acid cycle. The fluorine-substituted acetate is metabolized to fluoroci-trate that inhibits the conversion of citrate to isocitrate. There is an accumulation of large quantities of citrate in the tissue, and the cycle is blocked. The heart and central nervous system are the most critical tissues involved in poisoning by a general inhibition of oxidative energy metabolism. ... 

The result of this is that the pH difference and therefore potential difference across the membrane collapses, and there is no energy to drive the ATP synthesis. However, electrons can still flow through the chain, which drives the citric acid cycle to produce them, and so cellular metabolism still continues, and indeed, without the constraint of ATP synthesis, the electron flow is more rapid and so other metabolic rates also increase in rate. Oxygen can still be reduced to water, and so this will be used up also and require replacement. 

As noted earlier, although the citric acid cycle is central to energy-yielding metabolism its role is not limited to energy conservation. Four- and five-carbon intermediates of the cycle serve as precursors for a wide variety of products. To replace intermediates removed for this purpose, cells employ anaplerotic (replenishing) reactions, which are described below. 

The citric acid cycle (Krebs cycle, TCA cycle) is a nearly universal central catabolic pathway in which compounds derived from the breakdown of carbohydrates, fats, and proteins are oxidized to C02, with most of the energy of oxidation temporarily held in the electron carriers FADH2 and NADH. During aerobic metabolism, these electrons are transferred to 02 and the energy of electron flow is trapped as ATP. 

The production of acetyl-CoA for the citric acid cycle by the PDH complex is inhibited allosterically by metabolites that signal a sufficiency of metabolic energy (ATP, acetyl-CoA, NADH, and fatty acids) and stimulated by metabolites that indicate a reduced energy supply (AMP, NAD+, CoA). 

The same intermediates of glycolysis and the citric acid cycle that activate isocitrate dehydrogenase are allosteric inhibitors of isocitrate lyase. When energy-yielding metabolism is sufficiently fast to keep the concentrations of glycolytic and citric acid cycle intermediates low, isocitrate dehydrogenase is inactivated, the inhibition of isocitrate lyase is relieved, and isocitrate flows into the glyoxylate pathway, to be used in the biosynthesis of carbohydrates, amino acids, and other cellular components. 

Carbohydrate metabolism in a typical plant cell is more complex in several ways than that in a typical animal cell. The plant cell carries out the same processes that generate energy in animal cells (glycolysis, citric acid cycle, and oxidative phosphorylation) it can generate hexoses from three- or four-carbon compounds by glu-coneogenesis it can oxidize hexose phosphates to pentose phosphates with the generation of NADPH (the ox-... 

To replace losses, oxaloacetate can be synthesized from pyruvate and C02 in a reaction that uses ATP as an energy source. This is indicated by the heavy gray line leading downward to the right from pyruvate in Fig. 10-1 and at the top center of Fig. 10-6. This reaction depends upon yet another coenzyme, a bound form of the vitamin biotin. Pyruvate is formed from breakdown of carbohydrates such as glucose, and the need for oxaloacetate in the citric acid cycle makes the oxidation of fats in the human body dependent on the concurrent metabolism of carbohydrates. 

Fats, carbohydrates, and proteins are metabolized in the body to yield acetyl CoA, which is further degraded in the citric acid cycle to yield two molecules of CO2 plus a large amount of energy. The energy output of the various steps in the citric acid cycle is coupled to the electron-transport chain, a series of enzyme-catalyzed reactions whose ultimate purpose is to synthesize adenosine triphosphate (ATP). 

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