Synthetases fatty acid synthetase

We can descnbe the major elements of fatty acid biosynthesis by considering the for mation of butanoic acid from two molecules of acetyl coenzyme A The machinery responsible for accomplishing this conversion is a complex of enzymes known as fatty acid synthetase Certain portions of this complex referred to as acyl carrier protein (ACP), bear a side chain that is structurally similar to coenzyme A An important early step m fatty acid biosynthesis is the transfer of the acetyl group from a molecule of acetyl coenzyme A to the sulfhydryl group of acyl carrier protein... 

Fatty acid synthetase (Section 26 3) Complex of enzymes that catalyzes the biosynthesis of fatty acids from acetate Field effect (Section 19 6) An electronic effect in a molecule that IS transmitted from a substituent to a reaction site via the medium (e g solvent)... 

Biosynthesis of coen2yme A (CoA) ia mammalian cells incorporates pantothenic acid. Coen2yme A, an acyl group carrier, is a cofactor for various en2ymatic reactions and serves as either a hydrogen donor or an acceptor. Pantothenic acid is also a stmctural component of acyl carrier protein (AGP). AGP is an essential component of the fatty acid synthetase complex, and is therefore requited for fatty acid synthesis. Free pantothenic acid is isolated from hver, and is a pale yeUow, viscous, and hygroscopic oil. 

Fatty acid synthetase (Section 26.3) Complex of enzymes that catalyzes the biosynthesis of fatty acids from acetate. 

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. 

FIGURE 24.8 The mechanism of the acyl-CoA synthetase reaction involves fatty acid carboxylate attack on ATP to form an acyl-adenylate intermediate. The fatty acyl CoA thioester product is formed by CoA attack on this intermediate. 

Mammals can add additional double bonds to unsaturated fatty acids in their diets. Their ability to make arachidonic acid from linoleic acid is one example (Figure 25.15). This fatty acid is the precursor for prostaglandins and other biologically active derivatives such as leukotrienes. Synthesis involves formation of a linoleoyl ester of CoA from dietary linoleic acid, followed by introduction of a double bond at the 6-position. The triply unsaturated product is then elongated (by malonyl-CoA with a decarboxylation step) to yield a 20-carbon fatty acid with double bonds at the 8-, 11-, and 14-positions. A second desaturation reaction at the 5-position followed by an acyl-CoA synthetase reaction (Chapter 24) liberates the product, a 20-carbon fatty acid with double bonds at the 5-, 8-, IT, and ITpositions. 

Acyl-CoA synthetases are enzymes (i.e., ligases) that convert fatty acid molecules into acyl-Coenzyme A molecules for their subsequent oxidation. 

Gene activated Lipoprotein lipase fatty acid transporter protein adipocyte fatty acid binding protein acyl-CoA synthetase malic enzyme GLUT-4 glucose transporter phosphoenolpyruvate carboxykinase... 

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... 

The steps in the subsequent utilization of muscle LCFAs may be summarized as follows. The free fatty acids, liberated from triglycerides by a neutral triglyceride lipase, are activated to form acyl CoAs by the mediation of LCFAcyl-CoA synthetase which is situated on the outer mitochondrial membrane. The next step involves carnitine palmitoyl transferase I (CPT I, see Figure 9) which is also located on the outer mitochondrial membrane and catalyzes the transfer of LCFAcyl residues from CoA to carnitine (y-trimethyl-amino-P-hydroxybutyrate). LCFAcyl... 

The free fatty acids formed by lipolysis can be reconverted in the tissue to acyl-CoA by acyl-CoA synthetase and reesterified with glycerol 3-phosphate to form triacylglycerol. Thus, there is a continuous cycle of lipolysis and reesterification within the tissue. However, when the rate of reesterification is not sufficient to match the rate of lipolysis, free fatty acids accumulate and diffuse into the plasma, where they bind to albumin and raise the concentration of plasma free fatty acids. 

The fatty acids, as produced by intracellular hydrolysis of triacylglycerides or supplied to the cell from the blood, must be brought into a state of activation. Their activation is effected in the cytoplasm with the participation of acyl-CoA synthetase according to the scheme ... 

In the organism tissues, fatty acids are continually renewed in order to provide not only for the energy requirements, but also for the synthesis of multicomponent lipids (triacylglycerides, phospholipids, etc.). In the organism cells, fatty acids are resynthetized from simpler compounds through the aid of a supramolecular multienzyme complex referred to as fatty acid synthetase. At the Lynen laboratory, this synthetase was first isolated from yeast and then from the liver of birds and mammals. Since in mammals palmitic acid in this process is a major product, this multienzyme complex is also called palmitate synthetase. 

The cyclic process of fatty acid synthesis may be represented by a series of consecutive reactions (hereafter palmitate synthetase is... 

The key enzymes involved in the biosynthetic pathways of the Type I compounds are the fatty acid synthesis enzymes acetyl-CoA carboxylase and fatty acid synthetase. These enzymes are similar to those that produce the normal fatty acids used by all organisms. The resulting products are palmitic (16 car-... 

Specific chain length fatty acids could be produced in two ways. One is through the action of a thioester hydrolase that interacts with fatty acid synthetase to produce fatty acids shorter in length. Aphids produce myristic acid (14 carbons) and a specific thioester hydrolase releases the fatty acid from fatty acid synthetase after 6 additions of malonyl-CoA. If the hydrolase is not present then the fatty acid synthetase produces stearic acid [27]. A specific thioester hydrolase was ruled out in the biosynthesis of moth sex pheromones because labeling studies showed that longer chain length fatty acids were incorporated into shorter chain length pheromone components [22,28]. 

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,... 

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