Citric acid cycle degradation

C. The Citric Acid Cycle. Degradation of the 2-C body furnished by stage B to CO2. It is also known as the Krebs cycle after Krebs who, together with other scientists, elucidated this pathway a third name is tricarboxylic acid cycle which it owes to the participation of acids with three carboxyl functions. 

Enzymes work by bringing reactant molecules together, holding them, in the orientation necessary for reaction, and providing any necessary acidic or basic sites to catalyze specific steps. As an example, let s look at citrate synthase, an enzyme that catalyzes the aldol-like addition of acetyl CoA to oxaloacetate to give citrate. The reaction is the first step in the citric acid cycle, in which acetyl groups produced by degradation of food molecules are metabolized to yield C02 and H20. We ll look at the details of the citric acid cycle in Section 29.7. 

Figure 29.1 An overview of catabolic pathways for the degradation of food and the production of biochemical energy. The ultimate products of food catabolism are C02 and H2O, with the energy released in the citric acid cycle used to drive the endergonic synthesis of adenosine triphosphate (ATP) from adenosine diphosphate (ADP) plus phosphate ion, HOPO32-.

The catabolism of proteins is much more complex than that of fats and carbohydrates because each of the 20 amino acids is degraded through its own unique pathway. The general idea, however, is that the amino nitrogen atom is removed and the substance that remains is converted into a compound that enters the citric acid cycle. 

The primary fate of acetyl CoA under normal metabolic conditions is degradation in the citric acid cycle to yield C02. When the body is stressed by prolonged starvation, however, acetyl CoA is converted into compounds called ketone bodies, which can be used by the brain as a temporary fuel. Fill in the missing information indicated by the four question marks in the following biochemical pathway for the synthesis of ketone bodies from acetyl CoA ... 

Citric acid cycle (Section 29.7) The metabolic pathway by which acetyl CoA is degraded to CO2. 

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. 

Fig. 5.7. In green sulfur bacteria and in some archaebacteria, a reverse citric acid cycle is used for the assimilation of C02. It must be assumed that this was the original function of the citric acid cycle that only secondarily took over the role as a dissimulatory and oxidative process for the degradation of organic matter. A major enzyme here is 2-oxoglutarate ferredoxin for C02 fixation. Note that it, like several other enzymes in the cycle, uses Fe/S proteins. One is the initial so-called complex I which has eight different Fe/S centres of different kinds but no haem (see also other early electron-transfer chains, e.g. in hydrogenases).

Thiamine pyrophosphate is a coenzyme for several enzymes involved in carbohydrate metabolism. These enzymes either catalyze the decarboxylation of oi-keto acids or the rearrangement of the carbon skeletons of certain sugars. A particularly important example is provided by the conversion of pyruvic acid, an oi-keto acid, to acetic acid. The pyruvate dehydrogenase complex catalyzes this reaction. This is the key reaction that links the degradation of sugars to the citric acid cycle and fatty acid synthesis (chapters 16 and 18) ... 

The oxidation/reduction reactions that require one of the nicotinamide coenzymes are everywhere in metabolism in the glycolytic pathway, the citric acid cycle, the synthesis and degradation of fatty acids, the synthesis of steroids, and so on. Certain of... 

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 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. 

The Krebs cycle is sometimes still referred to as the citric acid cycle, citric acid being one of the intermediates involved, and even the tricarboxylic acid cycie, in that several of the intermediates are tri-acids. As the name suggests, the process is a cycle, so that there is a reasonably constant pool of intermediates functioning in an organism, and material for degradation is processed via this pool of intermediates. Overall, though, the material processed does not increase the size of the pool. The compound... 

Eugene Kennedy and Albert Lehninger showed in 1948 that, in eulcaiyotes, the entire set of reactions of the citric acid cycle takes place in mitochondria. Isolated mitochondria were found to contain not only all the enzymes and coenzymes required for the citric acid cycle, but also all the enzymes and proteins necessaiy for the last stage of respiration—electron transfer and ATP synthesis by oxidative phosphoiylation. As we shall see in later chapters, mitochondria also contain the enzymes for the oxidation of fatty acids and some amino acids to acetyl-CoA, and the oxidative degradation of other amino acids to a-ketoglutarate, succinyl-CoA, or oxaloacetate. Thus, in nonphotosynthetic eulcaiyotes, the mitochondrion is the site of most energy-yielding... 

The pathways of amino acid catabolism are quite similar in most organisms. The focus of this chapter is on the pathways in vertebrates, because these have received the most research attention. As in carbohydrate and fatty acid catabolism, the processes of amino acid degradation converge on the central catabolic pathways, with the carbon skeletons of most amino acids finding their way to the citric acid cycle. In some cases the reaction pathways of amino acid breakdown closely parallel steps in the catabolism of fatty acids (Chapter 17). 

The carbon skeletons of methionine, isoleucine, threonine, and valine are degraded by pathways that yield suc-cinyl-CoA (Fig. 18-27), an intermediate of the citric acid cycle. Methionine donates its methyl group to one of several possible acceptors through S-adenosytmethionine,... 

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. 

The carbon skeletons of amino acids enter the citric acid cycle through five intermediates acetyl-CoA, a-ketoglutarate, succinyl-CoA, fumarate, and oxaloacetate. Some are also degraded to pyruvate, which can be converted to either acetyl-CoA or oxaloacetate. 

Parallel Pathways for Amino Acid and Fatty Acid Degradation The carbon skeleton of leucine is degraded by a series of reactions closely analogous to those of the citric acid cycle and j8 oxidation. For each reaction, (a) through (f), indicate its type, provide an analogous example from the citric acid cycle or /3-oxidation pathway (where possible), and note any necessary cofactors. 

Amino acid degradation amino acids-----> acetyl-CoA, citric acid cycle intermediates... 

---