Carbon dioxide citric acid cycle

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. 

Catabolism converges via the citric acid cycle to three principal end products water, carbon dioxide, and ammonia. 

Ethanol is oxidized by alcohol dehydrogenase (in the presence of nicotinamide adenine dinucleotide [NAD]) or the microsomal ethanol oxidizing system (MEOS) (in the presence of reduced nicotinamide adenine dinucleotide phosphate [NADPH]). Acetaldehyde, the first product in ethanol oxidation, is metabolized to acetic acid by aldehyde dehydrogenase in the presence of NAD. Acetic acid is broken down through the citric acid cycle to carbon dioxide (CO2) and water (H2O). Impairment of the metabolism of acetaldehyde to acetic acid is the major mechanism of action of disulfiram for the treatment of alcoholism. 

Reverse citric acid cycle Incorporation of carbon dioxide ATP, QH2, haem... 

Q ttfiM In the citric acid cycle, every step that is an oxidation reaction also produces energy, until the most oxidized form of carbon leaves the cycle as carbon dioxide. Which steps in the cycle produce energy ... 

The citric acid cycle is at the heart of aerobic cellular metabolism, or respiration. This is true of both prokaryotic and eukaryotic organisms, of plants and animals, of organisms large and small. Here is the main point. On the one hand, the small molecule products of catabolism of carbohydrates, lipids, and amino acids feed into the citric acid cycle. There they are converted to the ultimate end products of catabolism, carbon dioxide and water. On the other hand, the molecules of the citric acid cycle are intermediates for carbohydrate, lipid, and amino acid synthesis. Thus, the citric acid cycle is said to be amphibolic, involved in both catabolism and anabolism. It is a sink for the products of degradation of carbohydrates, lipids, and proteins and a source of building blocks for them as well. 

In this reaction, pyruvic acid is oxidized to carbon dioxide with formation of acetyl-SCoA and NAD+ is reduced to NADH. As noted in chapter 15, this reaction requires the participation of thiamine pyrophosphate as coenzyme. Here too the NADH formed is converted back to NAD+ by the electron transport chain. As noted above, the acetyl-SCoA is consumed by the citric acid cycle and CoASH is regenerated. 

We should recognize that the citric acid cycle is catalytic. Specifically, the molecule that is required to condense with acetyl-SCoA in the first step of the cycle is regenerated in the last step. In principle therefore, the cycle is capable of consuming acetyl-SCoA and producing carbon dioxide endlessly as it turns. Here is a schematic... 

In summary, I have provided two examples of catabolic metabolic pathways linked to prodnction of ATP glycolysis, in which glucose is converted to lactate and pyrnvate and the citric acid cycle, in which acetate (derived from pyrnvate) is converted to carbon dioxide and water. In fact, these and other catabolic pathways generate more molecnles of ATP than 1 have so far let on. Now we need to do two things qnantitate the actnal yields of ATP and say something about how they are created. We begin by directing attention to the mitochondria. 

We still need to consider the outcome of converting the two molecules of acetyl-SCoA to carbon dioxide and water via the citric acid cycle. Each of these will yield a total 12 ATPmolecules one from a specific reaction in the cycle, nine from the oxidation of the three molecules of NADH, and two from the oxidation of one molecule of FADH2. So the two molecules of acetyl-SCoA will yield a total of 24 ATP molecules from two turns of the citric acid cycle. That brings the grand total to 14 - - 24 = 38 ATP molecules per molecule of glucose converted to carbon dioxide and water ... 

The complete oxidation of one molecule of glucose to carbon dioxide and water via glycolysis and the citric acid cycle generates 38 molecules... 

The tricarboxylic acid cycle (TCA cycle, also known as the citric acid cycle or Krebs cycle) is a cyclic metabolic pathway in the mitochondrial matrix (see p. 210). in eight steps, it oxidizes acetyl residues (CH3-CO-) to carbon dioxide (CO2). The reducing equivalents obtained in this process are transferred to NAD"" or ubiquinone, and from there to the respiratory chain (see p. 140). Additional metabolic functions of the cycle are discussed on p. 138. 

We have now seen how the 20 common amino acids, after losing their nitrogen atoms, are degraded by dehydrogenation, decarboxylation, and other reactions to yield portions of their carbon backbones in the form of six central metabolites that can enter the citric acid cycle. Those portions degraded to acetyl-CoA are completely oxidized to carbon dioxide and water, with generation of ATP by oxidative phosphorylation. 

One of the simplest biochemical addition reactions is the hydration of carbon dioxide to form carbonic acid, which is released from the zinc-containing carbonic anhydrase (left, Fig. 13-1) as HC03-. Aconitase (center, Fig. 13-4) is shown here removing a water molecule from isocitrate, an intermediate compound in the citric acid cycle. The H20 that is removed will become bonded to an iron atom of the Fe4S4 cluster at the active site as indicated by the black H20. An enolate anion derived from acetyl-CoA adds to the carbonyl group of oxaloacetate to form citrate in the active site of citrate synthase (right, Fig. 13-9) to initiate the citric acid cycle. 

It may be protested that the reaction of the citric acid cycle by which oxaloacetate is converted to oxo-glutarate does not follow exactly the pattern of Fig. 17-18. The carbon dioxide removed in the decarboxylation step does not come from the part of the molecule donated by the acetyl group but from that formed from oxaloacetate. However, the end result is the same. Furthermore, there are two known citrate-forming enzymes with different stereospecificities (Chapter 13), one of which leads to a biosynthetic pathway strictly according to the sequence of Fig. 17-18. 

Vitamin Influences. The involvement of NAD and NADP in many carbohydrate reactions explains the importance of nicotinamide in carbohydrate melaholism. Thiamine, in the form or thiamine pyrophosphate (cocarboxylase), is the cofaclor necessary in the decarboxylation of pyruvic acid, in the iraru-kelolase-calalyzed reactions of the pentose phosphaie cycle, and in the decarboxylation of alpha-keloglutaric acid in the citric acid cycle, among other reactions. Biotin is a hound cofaclor in the fixation of carbon dioxide to form nxalacetic acid from pyruvic acid. Pantothenic acid is a part of the C oA molecule. There are separate alphabetical entries in this volume on the various specific vitamins as well as a review entry on Vitamin. 

In most living organisms, the citric acid cycle constitutes the final common pathway in the degradation of foodstuffs anil cell constituents to carbon dioxide and water. This cycle is described In the entry-on Carbohydrates. 

Problem 6.2 illustrates the use of equation 6.2-1 by applying it to four net reactions that represent the oxidation of glucose to carbon dioxide and water (1) the net reaction for glycolysis, (2) the net reaction catalyzed by the pyruvate dehydrogenase complex, (3) the net reaction for the citric acid cycle, and (4) the net reaction for oxidative phosphorylation. The v in equation 6.2-1 is the apparent stoichiometric number matrix for these four reactions. The net reaction is... 

The first enzyme of the citric acid cycle to catalyze both the release of one carbon dioxide and the reduction of NAD+ is isocitrate dehydrogenase. The overall reaction of this step is as follows ... 

Acetyl-CoA is oxidized to carbon dioxide via the citric acid cycle (Chap. 12), thus transforming additional energy to that which has been transformed via /3-oxidation. In liver mitochondria only, acetyl-CoA may also be converted to ketone bodies ... 

You have already seen that citric acid is made from acetyl CoA. The acetyl CoA comes in its turn from pyruvic acid. Pyruvic acid comes from many sources but the most important is glycolysis acetyl CoA is the link between glycolysis and the citric acid cycle. The key reaction involves both Co ASH and pyruvate and carbon dioxide is lost. This is an oxidation as well and the oxidant is NAD+. The overall reaction is easily summarized. 

Most of the metabolites that serve as energy sources for aerobic organisms are broken down (catabo-lized) by various pathways to yield substrates for the central, energy-yielding citric acid cycle (also known as the tricarboxylic acid cycle or the Krebs cycle). The citric cycle is a sequence of enzymatic steps whose net reaction consists of the oxidation of acetate to carbon dioxide. 

The Krebs-citric acid cycle is the final common pathway for the oxidation of fuel molecules amino acids, fatty acids and carbohydrates. Most fuel molecules enter the cycle as a breakdown product, acetyl coenzyme A (acetyl CoA), which reacts with oxaloacetate (a four-carbon compound) to produce citrate (a six-carbon compound), which is then converted in a series of enzyme-catalysed steps back to oxaloacetate. In the process, two molecules of carbon dioxide and four energy-rich molecules are given off, and these latter are the precursors of the energy-rich molecule ATP, which is subsequently formed and which acts as the fuel source for all aerobic organisms. 

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