Long-chain acyl CoA

Eder, M., Krantle, R, Dong, Y, et al., 1997. Characterization of human and pig kidney long-chain-acyl-CoA dehydrogena.se.s and dieir role in beta-oxidation. European Journal of Biochemistry 245 600—607. 

Fatty acid transport protein paralogues 1-6 FATP 1-6 Gene symbols SLC27A1-6 Solute carrier family 27A Very long-chain acyl-CoA synthetase VLCS... 

Venus Flytrap Module Very Long-chain Acyl-CoA Synthetase Very Low-density Lipoprotein Vesicle... 

Long-chain fatty acids (e.g., palmitate Cig) diffuse through pores in the outer mitochondrial membrane, and then form long-chain acyl-CoA esters catalyzed reversibly by palmitoyl-CoA synthase (assumed to be on the inner face of the outer membrane). 

Long-chain acyl-CoA esters are then converted to acylcamitine esters by readily reversible reactions with L-camitine catalyzed by carnitine palmitoyltransferase I (CPT I). 

Enzymes 7,9, and 13 form a trifunctional protein associated with the inner face of the inner mitochondrial membrane. Very-long-chain acyl-CoA dehydrogenase is also associated with other inner mitochondrial membranes while the other enzymes are in the matrix and may be loosely associated with the inner face of the inner membrane. A medium-chain 2-enoyl-CoA hydratase may also be present in the mitochondrial matrix. 

Acetyl-CoA carboxylase T Insulin Citrate, insulin Long-chain acyl-CoA, cAMP, glucagon... 

Acetyl-CoA carboxylase is an allosteric enzyme and is activated by citrate, which increases in concentration in the well-fed state and is an indicator of a plentiful supply of acetyl-CoA. Citrate converts the enzyme from an inactive dimer to an active polymeric form, having a molecular mass of several milhon. Inactivation is promoted by phosphorylation of the enzyme and by long-chain acyl-CoA molecules, an example of negative feedback inhibition by a product of a reaction. Thus, if acyl-CoA accumulates because it is not esterified quickly enough or because of increased lipolysis or an influx of free fatty acids into the tissue, it will automatically reduce the synthesis of new fatty acid. Acyl-CoA may also inhibit the mitochondrial tricarboxylate transporter, thus preventing activation of the enzyme by egress of citrate from the mitochondria into the cytosol. 

Lipogenesis is regulated at the acetyl-CoA carboxylase step by allosteric modifiers, phosphorylation/de-phosphorylation, and induction and repression of enzyme synthesis. Citrate activates the enzyme, and long-chain acyl-CoA inhibits its activity. Insulin activates acetyl-CoA carboxylase whereas glucagon and epinephrine have opposite actions. 

Carnitine (p-hydroxy-y-trimethylammonium butyrate), (CHjljN"—CH2—CH(OH)—CH2—COO , is widely distributed and is particularly abundant in muscle. Long-chain acyl-CoA (or FFA) will not penetrate the inner membrane of mitochondria. However, carnitine palmitoyltransferase-I, present in the outer mitochondrial membrane, converts long-chain acyl-CoA to acylcarnitine, which is able to penetrate the inner membrane and gain access to the P-oxidation system of enzymes (Figure 22-1). Carnitine-acylcar-nitine translocase acts as an inner membrane exchange transporter. Acylcarnitine is transported in, coupled with the transport out of one molecule of carnitine. The acylcarnitine then reacts with CoA, cat-... 

Figure 22-1. Role of carnitine in the transport of long-chain fatty acids through the inner mitochondrial membrane. Long-chain acyl-CoA cannot pass through the inner mitochondrial membrane, but its metabolic product, acylcarnitine, can. 

Figure 22-3. 3-Oxidation of fatty acids. Long-chain acyl-CoA is cycled through reactions 2-5, acetyl-CoA being split off, each cycle, by thiolase (reaction 5). When the acyl radical is only four carbon atoms in length, two acetyl-CoA molecules are formed in reaction 5.

In M. rhodesianum no isoenzymes of the 3-ketothiolase have been found [ 14]. The enzyme s capability to react with long-chain acyl-CoAs has not been tested. The enzyme was found to be very similar to the 3-ketothiolases from R. eutropha, A. beijerinckii, Z. ramigera, and R. ruber with respect to molecular weight, optimum pH, and kinetic properties [14]. 

Herrmann, T., et al. Mouse fatty acid transport protein 4 (FATP4) characterization of the gene and functional assessment as a very long chain acyl-CoA synthetase. Gene 2001, 270,... 

Very-long-chain acyl-CoA dehydrogenase and trifunctional protein are the two inner membrane-bound... 

Monoacylglycerol lipase Long-chain acyl-CoA hydrolase... 

Thiolester hydrolases (EC 3.1.2) play an important role in the biochemistry of lipids. They catalyze the hydrolysis of acyl-coenzyme A thiolesters of various chain lengths to free fatty acids and coenzyme A. The current list of over 20 specific enzymes includes acetyl-CoA hydrolase (EC 3.1.2.1), pal-mi toy 1-Co A hydrolase (EC 3.1.2.2), and an acyl-CoA hydrolase (EC 3.1.2.20) of broad specificity for medium- to long-chain acyl-CoA [128],... 

Long-chain acyl-CoA synthetase activates fatty acids containing from 10 to 18 carbon atoms. 

A separate very long-chain-acyl-CoA synthetase is present in peroxisomes for the activation of very long-chain fatty acids, such as arachidonate (20 carbon atoms). These fatty acids are degraded exclusively in the peroxisomes. 

In addition, a high intracellular concentration of fatty acids raises that of long-chain acyl-CoA, which can damage... 

Figure 11.7 Synthesis of triaq/lglyceroL The precursors are glycerol 3-phosphate and long-chain acyl-CoA. R, is a saturated fatty acid, R2 is an unsaturated fatty acid (one or two doubte bonds) and R3 is either saturated or unsaturated. The activity of GPAT-1 regulates triacylglycerol synthesis. In all reactions involving RCO.SCoA, the CoASH is released but is not shown in this diagram. P,- - phosphate.

This enzyme [EC 6.2.1.15], also known as arachido-nateiCoA ligase, catalyzes the reaction of arachidonate with ATP and coenzyme A to generate arachidonyl-CoA, AMP, and pyrophosphate (or, diphosphate). The enzyme can also use 8,11,14-icosatrienoate as a substrate, but not the other long-chain fatty acids. It should be noted that this enzyme is not identical to long-chain acyl-CoA synthetase [EC 6.2.1.3]. 

This enzyme [EC 2.3.1.20], also known as diglyceride acyltransferase, catalyzes the reaction of an acyl-CoA with 1,2-diacylglycerol to produce coenzyme A and a triacylglycerol. The acyl-CoA derivative can be palmi-toyl-CoA or other long-chain acyl-CoA compounds. 

This enzyme [EC 1.3.99.13] catalyzes the reaction of a long-chain acyl-CoA with an electron-transferring fla-voprotein to produce a 2,3-dehydroacyl-CoA and the reduced electron-transferring flavoprotein. 

Kawashima Y, Uy-Yu N, Kozuka H Sex-related difference in the inductions by perfluorooctanoic acid of peroxisomal fl-oxidation, microsomal 1-acylglycerophos-phocholine acyltransferase and cytosolic long-chain acyl-CoA hydrolase in rat liver. Biochem J 26 595-6Q0, 1989... 

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