Tricarboxylic acid cycle, and

The 4-phosphopantetheine group of CoA is also utilized (for essentially the same purposes) in acyl carrier proteins (ACPs) involved in fatty acid biosynthesis (see Chapter 25). In acyl carrier proteins, the 4-phosphopantetheine is covalently linked to a serine hydroxyl group. Pantothenic acid is an essential factor for the metabolism of fat, protein, and carbohydrates in the tricarboxylic acid cycle and other pathways. In view of its universal importance in metabolism, it is surprising that pantothenic acid deficiencies are not a more serious problem in humans, but this vitamin is abundant in almost all foods, so that deficiencies are rarely observed. 

Argininosuccinate lyase (AL) (Fig. 40-5 reaction 4) cleaves argininosuccinate to form fumarate, which is oxidized in the tricarboxylic acid cycle, and arginine, which is hydrolyzed to urea and ornithine via hepatic arginase. Both AL and arginase are induced by starvation, dibutyryl cyclic-AMP and corticosteroids. 

The metabolic machinery responsible for the heterotrophic respiration reactions is contained in specialized organelles called mitochondria. These reactions occur in three stages (1) glycolysis, (2) the Krebs or tricarboxylic acid cycle, and (3) the process of oxidative phosphorylation also known as the electron transport chain. As illustrated in... 

NADH oxidation via complex I takes place on the inside of the membrane—i. e., in the matrix space, where the tricarboxylic acid cycle and 3-oxidation (the most important sources of NADH) are also located. O2 reduction and ATP formation also take place in the matrix. 

In eukaryotes, the cytoplasm, representing slightly more than 50% of the cell volume, is the most important cellular compartment. It is the central reaction space of the cell. This is where many important pathways of the intermediary metabolism take place—e.g., glycolysis, the pentose phosphate pathway, the majority of gluconeogenesis, and fatty acid synthesis. Protein biosynthesis (translation see p. 250) also takes place in the cytoplasm. By contrast, fatty acid degradation, the tricarboxylic acid cycle, and oxidative phosphorylation are located in the mitochondria (see p. 210). 

Red fibers provide for their ATP requirements mainly (but not exclusively) from fatty acids, which are broken down via 3-oxidation, the tricarboxylic acid cycle, and the respiratory chain (right part of the illustration). The red color in these fibers is due to the monomeric heme protein myoglobin, which they use as an O2 reserve. Myoglobin has a much higher af nity for O2 than hemoglobin and therefore only releases its O2 when there is a severe drop in O2 partial pressure (cf p.282). 

Many instances of stereospecific selection of enantiotopic groups or faces may be found in nature. One such is extracted from the tricarboxylic acid cycle and is shown in Exercise 1.6. At each step, achiral reactants are transformed to achiral products with high stereospecificity ... 

Fig. S.26. Summary of the potential energy released from oxidation of carbon materials to carbon dioxide and water via the tricarboxylic acid cycle and electronc transport in the...

We now explore the remarkable process by which a long-chain saturated fatty acid is converted into two-carbon units (acetate), which can be oxidized to C02 and H20 via the tricarboxylic acid cycle and the electron-transport chain. Fatty acids that enter cells are activated to their CoA derivatives by the enzyme acyl-CoA ligase and transported into the mitochondria for /3 oxidation as we discuss later in this chapter. 

Oxidation, in combination with the tricarboxylic acid cycle and respiratory chain, provides more energy per carbon atom than any other energy source, such as glucose and amino acids. The equations for the complete oxidation of palmitoyl-CoA are shown in table 18.1. Equation (1) in the table shows the oxidation of palmitoyl-CoA by the enzymes of j8 oxidation. Each of the products of equation (1) is further oxidized by the respiratory chain, equations (2) and (3), or by the tricarboxylic acid cycle and the respiratory chain, equation (4). When the reactions of equations (l)-(4) are summed, the result is equation (5). Hence, complete oxidation of one molecule of palmitoyl-CoA yields 108 ATP + 16C02 + 123 H20 and CoA. The water generated by /3 oxidation seems almost incidental to this process, but is crucial in several animal species. For example, the oxidation of fatty acids is used as a major source of H20 by the killer... 

In this section we have seen that fatty acids are oxidized in units of two carbon atoms. The immediate end products of this oxidation are FADH2 and NADH, which supply energy through the respiratory chain, and acetyl-CoA, which has multiple possible uses in addition to the generation of energy via the tricarboxylic acid cycle and respiratory chain. Unsaturated fatty acids can also be oxidized in the mitochondria with the help of auxiliary enzymes. Ketone body synthesis from acetyl-CoA is an important liver function for transfer of energy to other tissues, especially brain, when glucose levels are decreased as in diabetes or starvation. 

Acetyl-CoA. Acetyl-coenzyme A, a high-energy ester of acetic acid that is important both in the tricarboxylic acid cycle and in fatty acid biosynthesis. 

Succinic acid is a dicarboxylic acid produced as an intermediate of the tricarboxylic acid cycle and also as one of the fermentation products of anaerobic metabolism. It has been considered an important chemical because it can be used for the precursor of 1,4-butanediol, tetrahydrofu-ran, and y-butyrolactone as well as for application in polymers, foods, pharmaceuticals, and cosmetics (1,2). Currently, succinic acid is produced commercially through chemical synthesis. However, the production of... 

Fig. 11. Reactions in the tricarboxylic acid cycle and associated reactions. The unraveling of these reactions can be carried out using a combination of metabolite balancing and labeling experiments...

B. S. Sacktor and E. Wormser-Shavit, Regulation of metabolism in working muscle in vivo. I. Concentrations of some glycolytic, tricarboxylic acid cycle, and amino acid intermediates in insect flight muscle during flight, J. Biol. Chem., 241 (1966) 624-631. 

The mechanism of MCA toxicity seems to be via inhibition of the enzyme pyruvate dehydrogenase this inhibition blocks the Krebs (tricarboxylic acid) cycle and disrupts the cell s energy supply. Almost immediately, the cell finds itself without energy. Ketoglutarate dehydrogenase activity is also reduced, which causes lactic acidosis. The MCA also damages the blood-brain barrier, probably through the formation of vascular endothelial microlesions. 

---