Activation of fatty acids

At least three acyl-CoA synthases, each specific for a particular size of fatty acid, exist acetyl-CoA synthase acts on acetate and other low-molecular-weight carboxylic acids, medium-chain acyl-CoA synthase on fatty acids with 4-11 carbon atoms, and acyl-CoA synthase on fatty acids with 6-20 carbon atoms. The activity of acetyl-CoA synthase in muscle is restricted to the mitochondrial matrix. Medium-chain acyl-CoA synthase occurs only in liver mitochondria, where medium-chain fatty acids obtained from digestion of dietary triacylglycerols and transported by the portal blood are metabolized. Acyl-CoA synthase, the major activating enzyme, occurs on the outer mitochondrial membrane surface and in endoplasmic reticulum. The overall reaction of activation is as follows  

The reaction favors the formation of fatty acyl-CoA, since the pyrophosphate formed is hydrolyzed by pyrophosphatase PPj-fH20- 2Pj. Thus, activation of a fatty 

A mitochondrial acyl-CoA synthase, which utilizes GTP, has also been identified  

The standard free-energy change of this reaction is about zero, and therefore the O-ester bond of acylcamitine may be considered as a high-energy linkage. Malonyl-CoA, a precursor in the synthesis of fatty acids, is an allosteric inhibitor of CPTI in liver and thus prevents a futile cycle of simultaneous fatty acid oxidation and synthesis. 

Four inherited defects of carnitine metabolism lead to impaired utilization of long-chain fatty acids for energy production. These include defects of plasma 

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Another way in which the phosphorylation state of the adenylate system can regulate the cycle depends upon the need for GDP in step/of the cycle (Fig. 17-4). Within mitochondria, GTP is used largely to reconvert AMP to ADP. Consequently, formation of GDP is promoted by AMP, a compound that arises in mitochondria from the utilization of ATP for activation of fatty acids (Eq. 13-44) and activation of amino acids for protein synthesis (Eq. 17-36). 

The AG° values for the hydrolysis of any P - O - P bond of ATP, inorganic pyrophosphate, or any acyl CoA thiolester are all about -34 kj / mole, while the corresponding figure for the hydrolysis of a mixed carboxylic phosphate anhydride is about -55 kj / mole. Calculate the value of AG° for the following reaction describing the activation of fatty acids to the fatty acyl adenylate. 

Proposed organization of the enzymatic activities of fatty acid synthase from animal liver. Fatty acid synthase exists as a dimer of two giant identical peptides (Mr = 272,000). Each subunit has one copy of acyl carrier protein (ACP) and each of the enzyme activities involved in fatty acid synthesis is covalently linked. The two peptides are organized in a head-to-tail configuration in such a way that it is possible to make two fatty acid molecules at the same time. 

Shibasaki, I., and N. Kato. 1978. Combined effects on antibacterial activity of fatty acids and their esters against gram-negative bacteria. In The pharmacological effects of lipids, ed. J.J. Kabara, 15-24. St. Louis American Oil Chemists Society. 

OXIDATION OF FATTY ACIDS 19.4.1 Activation of Fatty Acids... 

Manoharan, L, Boopathy, R. (2006). Diisopropylflurophosphate-sensitive aryl acylamidase activity of fatty acid free human serum albumin. Arch. Biochem. Biophys. 452 186-8. 

T. G. Cooper, J. Biol. Chem., 246 3451 (1971). The Activation of Fatty Acids in Castor Bean Endosperm. 

The perturbation of the intercellular lipid bilayers in the stratum corneum seems to be the most important reason for the enhancing activity of fatty acids such as oleic acid. Oleic acid has been described to decrease the phase transition temperatures of the skin lipids... 

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). 

This hepatomegaly is correlated to PPARa activation of acyl-CoA oxidase (AOX), the first enzyme of peroxisomal /3-oxidation of fatty acids and a gene with a PPRE in its promoter region14. In addition, hepatic mitochondrial /3-oxidation and microsomal w-oxidation of fatty acids are increased, as a direct result of PPARa activation of mRNA of specific enzymes associated with these pathways (carnitine palmitoyl transferase I and cytochrome P4504A, respectively). Activation of fatty acid oxidation by these three pathways would lead to enhanced fatty acid oxidation, given the appropriate substrate. PPARa has also been shown to enhance delivery of fatty acids to the oxidizing systems (Fig. 3). 

Lichtman AH, Hawkins EG, Griffin G, Cravatt BF (2002) Pharmacological activity of fatty acid amides is regulated, but not mediated, by fatty acid amide hydrolase in vivo. J Pharmacol Exp Ther 302 73-79... 

The pyrophosphate hydrolysis, although not coupled to any particular endergonic reaction, still ensures completion of the forward reaction or process (e.g., activation of fatty acids and amino acids, synthesis of nucleotides and polynucleotides). 

Which of the following regulates lipolysis in adipocytes Activation of fatty acid synthesis mediated by cyclic AMP... 

Figure 36-4. The activation of fatty acids and transport into the mitochondrion via the carnitine shuttle. (Reproduced, with permission, from D.B. Marks, et al, Basic Medical Biochemistry A Clinical Approach, Philadelphia Lippincott...

Enzymes. The structures of both acetyl-CoA carboxylase and fatty acid synthase in plants more closely resemble their counterparts in Escherichia coli than those in animal cells. For example, in E. coli and plants, each of the enzyme activities of fatty acid synthase is found on a separate protein. 

Yang, Y. A., Han, W. F., Morin, P. J., Chrest, F. J. and Pizer, E. S., Activation of fatty acid synthesis during neoplastic transformation role of mitogen-activated protein kinase and phosphatidylinositol 3-kinase, Exp Cell Res 279 (2002) 80-90. 

Uptake and activation of fatty acids in animal cells. 132... 

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