Pyrophosphate fatty acid oxidation

The metabolic functions of pantothenic acid in human biochemistry are mediated through the synthesis of CoA. Pantothenic acid is a structural component of CoA. which is necessary for many important metabolic processes. Pantothenic acid is incorporated into CoA by a. series of five enzyme-catalyzed reactions. CoA is involved in the activation of fatty acids before oxidation, which requires ATP to form the respective fatty ocyl-CoA derivatives. Pantothenic acid aI.so participates in fatty acid oxidation in the final step, forming acetyl-CoA. Acetyl-CoA is also formed from pyruvate decarboxylation, in which CoA participates with thiamine pyrophosphate and lipoic acid, two other important coenzymes. Thiamine pyrophosphate is the actual decarboxylating coenzyme that functions with lipoic acid to form acetyidihydrolipoic acid from pyruvate decarboxylation. CoA then accepts the acetyl group from acetyidihydrolipoic acid to form acetyl-CoA. Acetyl-CoA is an acetyl donor in many processes and is the precursor in important biosyntheses (e.g.. those of fatty acids, steroids, porphyrins, and acetylcholine). 

Identification and quantitative analyses of 25 compounds in steam distillates of burley tobacco stalk were accomplished. Compounds included twelve C,-C. compounds that were probable fatty acid oxidation products and 13 compounds >C that varied in origin. The latter included oxidation products of fatty acids, a C. prenyl pyrophosphate metabolite, and biodegradation products of carotenoids and chlorophyll. About 1/3 of the distillate mass was accounted for. Burley tobacco stalk headspace volatiles were also studied. When compared to the steam distillate, the headspace contained greater concentrations of sesquiterpenoids but lower concentrations of C, and C aldehydes and alcohols. Volatiles in steam distillates of tobacco stalk were not quantitatively different in a fungal resistant and a fungal sensitive variety of tobacco. Yield comparisons were made of headspace volatiles from tobacco and wheat. 

Now that we have completed this analytical examination of the enzymes involved in fatty acid oxidation, it is possible to take a synthetic view of the pathway as it is outlined in Fig. 1-23. On examination of that figure, it is obvious that two metabolites—ATP and oxaloacetate—provided by the Krebs cycle, are needed for proper functioning of the fatty acid oxidation pathway. ATP is required in the thiokinase reaction where the free energy of the pyrophosphate is used to activate the fatty acid, and oxaloacetate escorts acetyl-CoA through the Krebs cycle. 

Points worth noting are (1) All the reactants are acyl derivatives of CoA. (2) All the enzymes are localized within the mitochondria with those of the citrate cycle and electron-transport chain. This ensures efficient utilization of the acetyl-CoA released by the fatty acid oxidation. (3) Only one activation step is necessary, regardless of the length of the fatty acid chain. This uses two high-energy bonds, since ATP is broken down to AMP and pyrophosphate during the thiokinase reaction. 

FIGURE 24.7 The acyl-CoA synthetase reaction activates fatty acids for /3-oxidation. The reaction is driven by hydrolysis of ATP to AMP and pyrophosphate and by the subsequent hydrolysis of pyrophosphate. 

The answer is d. (Murray, pp 230-267. Scriver, pp 2297-2326. Sack, pp 121-138. Wilson, pp 287-320.) Fatty acids must be activated before being oxidized. In this process, they are linked to CoA in a reaction catalyzed by thiokinase (also known as acyl CoA synthetase). ATP is hydrolyzed to AMP plus pyrophosphate in this reaction. In contrast, the enzyme thiolase cleaves off acetyl CoA units from p-ketoacyl CoA, while it forms thioesters during P oxidation. 

Fatty acids must be activated to acyl CoA derivatives before they can participate in 3-oxidation and other metabolic pathways (Fig. 23.2). The process of activation involves an acyl CoA synthetase (also called a thiokinase) that uses ATP energy to form the fatty acyl CoA thioester bond. In this reaction, the p bond of ATP is cleaved to form a fatty acyl AMP intermediate and pyrophosphate (PPi). Subsequent cleavage of PPi helps to drive the reaction. 

Quinones are firmly established in photosynthesis models. But how about vitamins E and K How do quinones work in animals First of all they transport electrons in a similar way as in photosynthesis (Metzler, 1977 Voet, 1990). Second, tocopherol is known to act as an antioxidant or radical quencher. The radical chain starting with the decomposition of unsaturated lipid peroxides, for example, is inhibited by tocopherol, which produces long-lived semiquinone radicals (Scheme 7.2.10). Vitamin E prevents, for example, sterility in rats fed rancid lipids. Vitamin E in connection with carotenes is also used as a stabilizer for diet margarines containing large amounts of essential fatty acids. Another possible activity of tocopherol is participation in oxidative phosphorylation a hydroquinone is mono-esterified with phosphoric acid to form a quinol phosphate and then oxidized to the quinone. The cationic quinone-phosphate adduct then reacts with anionic phosphate to form pyrophosphate (Scheme 7.2.10), (Wang, 1969 Breslow, 1980 Isler and Brubacher, 1982). 

Malik presented data [27] on the detergency of C12 and C13.6 SMEs via a modified Gardner Straight Line Washability Test [39]. The test solutions consisted of 0.6% of the test surfactant and 0.12% tetrapotassium pyrophosphate in 140 ppm as CaCOj water at 25°C. The C12 SME gave equivalent performance compared to decyl and branched dodecyl diphenyl oxide disulfonates. The Cl3.6 SME slightly outperformed the Cl2 SME but was not quite as good as the C8-10, 5-mole ethoxylated phosphate ester that was also included. Both SMEs contained the analog sulfonated fatty-acid sodium salts as secondary snrfactants. 

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