Fatty acyl-coenzyme

Thioesters play a paramount biochemical role in the metabolism of fatty acids and lipids. Indeed, fatty acyl-coenzyme A thioesters are pivotal in fatty acid anabolism and catabolism, in protein acylation, and in the synthesis of triacylglycerols, phospholipids and cholesterol esters [145], It is in these reactions that the peculiar reactivity of thioesters is of such significance. Many hydrolases, and mainly mitochondrial thiolester hydrolases (EC 3.1.2), are able to cleave thioesters. In addition, cholinesterases and carboxylesterases show some activity, but this is not a constant property of these enzymes since, for example, carboxylesterases from human monocytes were found to be inactive toward some endogenous thioesters [35] [146], In contrast, allococaine benzoyl thioester was found to be a good substrate of pig liver esterase, human and mouse butyrylcholinesterase, and mouse acetylcholinesterase [147],... 

Hazel, J.R. and Livermore, R.C. (1990). Fatty-acyl coenzyme A pool in liver of rainbow trout, Salmo gairdneri. Effects of temperature acclimation. Journal of Experimental Zoology 256,31-37. 

Varanasi U, Chu R, Huang Q, et al. 1996. Identification of a peroxisome proliferator-responsive element upstream ofthe human peroxisomal fatty acyl coenzyme A oxidase gene. J Biol Chem271 2147-2155. 

X and Y are other ubiquinone-reducing flavoproteins (eg. from a glycerophosphate cr fatty acyl coenzyme A). 

LeFlir M, Dubach U. Peroxisomal and mitochondrial b-oxidation in the rat kidney. Distribution of fatty acyl coenzyme A oxidase and 3-hydroxyacyl-coenzyme A dehydrogenase activities along the nephron. J Flistochem Cytochem 1982 30 441-444. 

Coenzyme A Fatty acyl-coenzyme A FIGURE 5.14 Removal of the finished fatty acid from the enzyme. 

The average intake of pantothenic acid, as free pantothernc acid and as coenzyme A, acetyl-coenzyme A, and long-chain fatty acyl-coenzyme A, is 5 to 10 mg/day. An RDA for the vitamin has not been established because the vitamin is plentiful in a variety of foods. Pantothenic acid is present in all plant and animal foods. The richest sources of the vitamin are liver, yeast, egg yolk, and vegetables. In foods, the vitamin occurs mainly as coenz5rme A. 

The concentration of free pantothenic acid in the liver is about 15 xM that in the heart is about tenfold greater (Robishaw and Neely, 1985). The concentration of the cofactor form of the vitamin, coenzyme A, is higher in the mitochondrion than in the cytosol. In the Ever, cytosolic coenzyme A is about 0.06 mM, and mitochondrial coenzjmie A, about 2.6 mM. In the liver, about 70% of coenzyme A is mitochondrial, whereas in the heart about 95% is mitochondrial (Tahiliani and Neely, 1987). These values might be compared with that for carnitine, another molecule used in the handling of fatty acids. Please consult the Carnitine section in Chapter Four. About half of the coenzjrme A in liver occurs as the long-chain fatty acyl-coenzyme A derivative. The concentration of fatty acid s)mthase in the cytoplasm is quite low, about 0.01 pM. Hence, the concentration of the 4 -phospho-pantetheine cofactor is much lower than that of coenzyme A. The pantothenic acid boimd to this enzyme does not make a significant contribution to our dietary vitamin. 

Several pharmacogenomic studies, mainly in animal models, have characterized the molecular mechanisms contributing to the lipidlowering effect of fibrates. Hepatic transcription profiling of clofibrate or gemfibrozil-treated WT rats demonstrated increased expression of many genes involved in beta-oxidation, as well as FFA and cholesterol synthesis, including fatty acyl-Coenzyme A oxidase [45, 191, 192], acetyl-Coenzyme A acetyltransferase... 

Synthesis of phosphatidylcholine. The rate-limiting reaction is that catalyzed by cytidylyltransferase (reaction 2) which appears to be active only when attached to the endoplasmic reticulum, although it is also found free in the cytosol. Cytidylyltransferase is inactivated by a cAMP-dependent protein kinase and activated by a phosphatase. Translocation to the endoplasmic reticulum can be stimulated by substrates such as fatty acyl Coenzyme A (CoA). Choline deficiency can result in deposition of triacylglycerol in liver and reduced phospholipid synthesis. Enzymes (1) choline kinase ... 

Seedorf, U., Raabe, M., Ellinghaus, P., Kannenberg, F., Fobker, M., Engel, T., Denis, S., Wouters, E., Wirtz, K. W., Wanders, R. J., et al. Defective peroxisomal catabohsm of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function. Genes Dev 12 (1998) 1189-1201. 

Pfanner, N., Orci, L., Glick, B.S., Amherdt, M., Arden, S.R., Malhotra, V. Rothman, J.E. (1989) Cell, 59, 95-102. Fatty acyl-coenzyme A is required for budding of transport vesicles from Golgi cistemae. 

Fatty acyl-coenzyme A is required for budding of transport vesicles from Golgi cistemae. 

Morell, P. Radin, N.S. (1970) Specificity in Ceramide Biosynthesis from Long Chain Basis and Various Fatty Acyl Coenzyme A s by Brain Microsomes , Journal of Biological Chemistry 245, 342-50... 

In the final stages of this fat synthesis, fatty acyl coenzyme A molecnles react with a-glycero-phosphoric acid to give phosphatidic acid, which is a chiral compound by virtue of the asymmetric carbon C (11.98). Phosphatidic acid can now be hydrolysed to yield a 1,2 diacylglycerol which will react with another molecule of fatty acyl coenzyme A to give a triacylglycerol according to (11.99). 

This figure shows the way in which glucose or fatty acids (in the form of fatty acyl coenzyme A, acyl CoA) are utilised as a source of energy by tissue. It shows the incorporation of acetyl CoA into the citric acid cycle, and also the points at which connections are made with other areas of metabolism. Amino... 

Activated fatty acids fatty acyl coenzyme A thioesters which, as high energy compounds, have a high potential for group transfer. They are formed during fatty acid biosynthesis, or by the activation of free fatty acids. Acyl CoA synthetases catalyse formation of the CoA derivatives according to the... 

Thioester, acylmercaptan a compound of the general formula RS - CO-R,. The thioester (acylmercaptan) bond is energy-rich. All fatty acyl coenzyme A derivatives (activated fatty acids, e.g. acetyl-CoA) are T. During substrate phosphorylation on glyceral-dehyde 3-phosphate dehydrogenase a thiol group of the enzyme forms an energy-rich intermediate T. 

These finding brought triglyceride synthesis in line with the synthesis of phospholipids, which was shown by Smith et al. (1957) to proceed by removal of the phosphate from phosphatidic acid, with the formation of an a )3-diglyceride. Diglyceride can now be converted into phospholipid, by cytidine-diphosphate-choline or ethanolamine (Kennedy and Weiss 1956) or into neutral triglycerides by the addition of one more fatty acid, derived from fatty acyl-coenzyme A. (Weiss and Kennedy 1956, 1960). 

Haynes, C.A., Allegood, J.C., Sims, K., Wang, E.W., Sullards, M.C. and Merrill, A.H., Ir. (2008) Quantitation of fatty acyl-coenzyme As in mammalian cells by liquid chromatography-electrospray ionization tandem mass spectrometry. J. Lipid Res. 49, 1113-1125. 

Pfanner, N., Ord, L., GMck, B.S., Amherdt, M., Arden, S.R., Malhotra, V. Rothman, J.E. (1989) Cell, 59, 95-102. Fatty acyl-coenzyme A is required for budding of transport vesicles from Golgi dstemae. Rothman, J.E. Ord, L. (1992) Nature, 355, 409-415. Molecular dissection of the secretory pathway. Ostermann, J., Ord, L., Tani, K., Amherdt, M., Ravazzola, M., Elazar, Z. Rothman, J.E. (1993) Cell, 75, 1015-1025. Stepwise assembly of functionally active transport vesicles. 

Bishop, JE, and Hajra, AK. A method for the chemical synthesis of C-labeled fatty acyl coenzyme A s of high specific activity. Analytical Biochemistry 1980 106 344-350... 

Metz, J.G., Pollard, M.R., Anderson, L., Hayes, T.R., Lassner, M.W., 2000. Purification of a jojoba embryo fatty acyl-coenzyme A reductase and expression of its cDNA in high erucic acid rape-seed. Plant Physiol. 122, 635-644. 

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