Citric acid cycle metabolic importance

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 number of vitamin B 12-dependent reactions is not large. Most of these involve rearrangements of the carbon skeletons of metabolites. Such reactions are important in linking some aspects of fatty acid metabolism to the citric acid cycle. In another form, a vitamin Bi2-derived coenzyme is involved, along with folic acid coenzymes, in the metabolism of one-carbon fragments, including the biosynthesis of methionine. 

Acetoacetyl-CoA appears to be in equilibrium with acetyl-CoA within the body and is an important metabolic intermediate. It can be cleaved to two molecules of acetyl-CoA which can enter the citric acid cycle. 

The conversion of fumaric acid to malic acid is an important biological hydration reaction. It is one of a cycle of reactions (Krebs citric acid cycle) involved in the metabolic combustion of fuels (amino acids and carbohydrates) to C02 and H20 in a living cell. 

This transfer of reducing equivalents is essential for maintaining the favorable NAD+/NADH ratio required for the oxidative metabolism of glucose and synthesis of glutamate in brain (McKenna et al., 2006). The malate-aspartate shuttle is considered the most important shuttle in brain. It is particularly important in neurons. It has low activity in astrocytes. This shuttle system is fully reversible and linked to amino acid metabolism with the energy charge and citric acid cycle of neuronal cells. 

Mitochondria arc membranous organelles (Fig. 1-9) of great importance in the energy metabolism of the cell they are the source of most of the ATP (Chap. 14) and the site of many metabolic reactions. Specifically, they contain the enzymes of the citric acid cycle (Chap. 12) and the electron-transport chain (Chap. 14), which includes the main oxygen-utilizing reaction of the cell. A mammalian liver cell contains about 1.000 of these organelles about 20 percent of the cytoplasmic volume is mitochondrial. 

The tricarboxylic acid (TCA) cycle (also known as the citric acid cycle and the Krebs cycle) is a collection of biochemical reactions that oxidize certain organic molecules, generating CO2 and reducing the cofactors NAD and FAD to NADH and FADH2 [147], In turn, NADH and FADH2 donate electrons in the electron transport chain, an important component of oxidative ATP synthesis. The TCA cycle also serves to feed precursors to a number of important biosynthetic pathways, making it a critical hub in metabolism [147] for aerobic organisms. Its ubiquity and importance make it a useful example for the development of a kinetic network model. 

The citric acid cycle is the central metabolic hub of the cell. It is the gateway to the aerobic metabolism of any molecule that can be transformed into an acetyl group or dicarboxylic acid. The cycle is also an important source of precursors, not only for the storage forms of fuels, but also for the building blocks of many other molecules such as amino acids, nucleotide bases, cholesterol, and porphyrin (the organic component of heme). 

The citric acid cycle is the final common pathway for the aerobic oxidation of fuel molecules. Moreover, as we will see shortly (Section 17.3) and repeatedly elsewhere in our study of biochemistry, the cycle is an important source of building blocks for a host of important biomolecules. As befits its role as the metabolic hub of the cell, entry into the cycle and the rate of the cycle itself are controlled at several stages. 

When the cell has adequate energy available, the citric acid cycle can also provide a source of building blocks for a host of important biomolecules, such as nucleotide bases, proteins, and heme groups. This use depletes the cycle of intermediates. When the cycle again needs to metabolize fuel, anaplerotic reactions replenish the cycle intermediates. 

We now turn to the fates of the carbon skeletons of amino acids after the removal of the a-amino group. The strategy of amino acid degradation is to transform the carbon skeletons into major metabolic intermediates that can be converted into glucose or oxidized by the citric acid cycle. The conversion pathways range from extremely simple to quite complex. The carbon skeletons of the diverse set of 20 fundamental amino acids are furmeled into only seven molecules pyruvate, acetyl CoA, acetoacetyl CoA, a-ketoglutarate, succinyl CoA, fumarate, and oxaloacetate. We see here a striking example of the remarkable economy of metabolic conversions, as well as an illustration of the importance of certain metabolites. 

The answer is c. (Murray, pp 627-661. Scriver, pp 3897-3964. Sack, pp 121-138. Wilson, pp 287-320.) Certain amino acids and lipids are dietary necessities because humans cannot synthesize them. The energy usually obtained from carbohydrates can be obtained from lipids and the conversion of some amino acids to intermediates of the citric acid cycle. These alternative substrates can thus provide fuel for oxidation and energy plus reducing equivalents for biosynthesis. Iodine is important for thyroid hormone synthesis, while calcium is essential for muscle contraction and bone metabolism. 

All these proteins give a typical Mossbauer spectrum in the reduced form identical to that obtained for D.gigas Fdll. Aconitase contains only one type of iron-sulfur center. While ferredoxins are only involved in electron transfer, aconitase has a central metabolic role in the citric acid cycle 37>68h The role of the iron-sulfur center remains to be determined. Glutamate synthase is an important enzyme in... 

In addition to its role in energy production, the citric acid cycle plays another important role in metabolism. Cycle intermediates are substrates in a variety of biosynthetic reactions. Table 9.2 provides a summary of the roles of coenzymes in the citric acid cycle. 

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