Citric acid cycle features

One of the great unifying features of life is the similarity in metabolic patterns. As diverse as life forms are, their patterns of metabolic activity— how molecules are formed and degraded—are remarkably closely related. That is not to say that they are identical. They are not. Indeed, identity in metabolic pattern would imply identity in structure and physiology, which is certainly not the case. Nonetheless, the similarities are striking. Variations on a unified central metabolic theme give rise to the diversity of life forms. Nowhere is this fundamental fact more clearly evident than in the central metabolic pathway known as the citric acid cycle. 

The enzyme isocitrate dehydrogenase is one of the enzymes of the Krebs or citric acid cycle, a major feature in carbohydrate metabolism (see Section 15.3). This enzyme has two functions, the major one being the dehydrogenation (oxidation) of the secondary alcohol group in isocitric acid to a ketone, forming oxalosuccinic acid. This requires the cofactor NAD+ (see Section 11.2). For convenience, we are showing non-ionized acids here, e.g. isocitric acid, rather than anions, e.g. isocitrate. 

This irreversible reaction is the link between glycolysis and the citric acid cycle. (Figure 17.4) Note that, in the preparation of the glucose derivative pyruvate for the citric acid cycle, an oxidative decarboxylation takes place and high-transfer-potential electrons in the form of NADH are captured. Thus, the pyruvate dehydrogenase reaction has many of the key features of the reactions of the citric acid cycle itself... 

Thus far, we have considered the conversion of N2 into NH4 + and the assimilation of NH4 + into glutamate and glutamine. We turn now to the biosynthesis of the other amino acids. The pathways for the biosynthesis of amino acids are diverse. However, they have an important common feature their carbon skeletons come from intermediates of glycolysis, the pentose phosphate pathway, or the citric acid cycle. On the basis of these starting materials, amino acids can be grouped into six biosynthetic families (Figure 24.7). 

Because carbohydrate utilization is impaired, a lack of insulin leads to the uncontrolled breakdown of lipids and proteins. Large amounts of acetyl CoA are then produced by P-oxidation. However, much of the acetyl CoA cannot enter the citric acid cycle, because there is insufficient oxaloacetate for the condensation step. Recall that mammals can synthesize oxaloacetate from pyruvate, a product of glycolysis, but not from acetyl CoA instead, they generate ketone bodies. A striking feature of diabetes is the shift in fuel usage from carbohydrates to fats glucose, more abundant than ever, is spurned. In high concentrations, ketone bodies overwhelm the kidney s capacity to maintain acid-base balance. The untreated diabetic can go into a coma because of a lowered blood pH level and dehydration. 

Step 2. Isomerization of Citrate to Isocitrate The second reaction of the citric acid cycle, the one catalyzed by aconitase, is the isomerization of citrate to isocitrate. The enzyme requires Fe +. One of the most interesting features of the reaction is that citrate, a symmetrical (achiral) compound, is converted to isocitrate, a chiral compound, a molecule that cannot be superimposed on its mirror image. 

Some important features of the citric acid cycle are the following ... 

The citric acid cycle has been found to take place in microorganisms and plant seedlings as well as in the cells of animals. The existence of this common feature, as well as others, indicates a common origin, as is assumed in the theory of evolution. There is evidence that for some microorganisms the cycle serves mainly to produce molecules with special structure for special purposes (such as a-ketoglutaric acid for the synthesis of glutamic acid and some other amino acids). For man and other animals it supplies both these special substances and energy. 

Some reactions of thiamine, such as decarboxylation of a-oxocarboxylic acids, are features of primary metabolism (decarboxylation of pyruvic acid to acetaldehyde in glycolysis and transformation of pyruvic acid to acetyl-CoA prior to its entry into the citric acid cycle) that depend on thiamine diphosphate as a coenzyme. The thiamine ring has an acidic hydrogen and is thus capable of producing the carbanion that acts as a nucleophile towards carbonyl groups. Analogous reactions proceed non-enzymatically and can thus be included among the so-called... 

The essential feature of the cycle is that the 2-carbon fragment of acetyl-CoA is made to combine with a 4-carbon acid, to yield the very reactive 6-carbon citric acid molecule. This reaction, necessitating as it does the formation of a carbon-carbon bond, is... 

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