Acyl synthetase

Fatty acyl synthetase activates the fatty add (outer mitochondrial membrane). 

Answer C. CAT-1 (CPT-1) and fatty acyl synthetase are among the few enzymes associated with the outer mitochondrial membrane. 

The first step in this preparation consists of the activation of the amino acids, so as to prime them with sufficient energy fpr the subsequent formation of peptide bonds. This activation is performed at the expense of ATP by a series of amino acyl synthetase enzymes, one for each amino acid. These enzymes were reported... 

Figure 2. Effect of CoASH on acyl-synthetase activity in leek microsomes. Acyl- CoA synthetase was measured in the presence of [ C]18 0, ATP, Mg- ...

The symbols utilized indicate AA = aminoacid AAS = amino-acyl synthetase ATP = adenosinetriphosphate GDP = guano-sinediphosphate GTP = guanosinetriphosphate 40 S and 60 S =... 

There are two main types of FAS Type I FAS occurring in animals, fimgi, protozoa and some bacteria, and type II characteristic of bacteria and green plants including algae. Type I FAS are stable, high molecular weight (410,000 to 2 x 10 daltons) multifunctional complexes. The enzyme from mammals and birds consists of two subunits, each of which can catalyze all steps in fatty acid synthesis except for condensation (P-keto-acyl synthetase). Dimerization restores this activity. 

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... 

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. 

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... 

Acyl-CoA Synthetase Adaptive Immunity Adaptor Proteins Addiction Addison s Disease Additive Interaction Adenosine Adenosine Receptors Adenoviruses Adenylate Cyclase Adenylyl Cyclases ADH ADHD... 

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

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... 

Mitochondria have an outer membrane that is permeable to most metabohtes, an inner membrane that is selectively permeable, and a matrix within (Figure 12-1). The outer membrane is characterized by the presence of various enzymes, including acyl-CoA synthetase and glycerolphosphate acyltransferase. Adenylyl kinase and creatine kinase are found in the intermembrane space. The phospholipid cardiolipin is concentrated in the inner membrane together with the enzymes of the respiratory chain. 

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 P-alanyl dipeptides carnosine and anserine (A -methylcarnosine) (Figure 31-2) activate myosin ATPase, chelate copper, and enhance copper uptake. P-Alanyl-imidazole buffers the pH of anaerobically contracting skeletal muscle. Biosynthesis of carnosine is catalyzed by carnosine synthetase in a two-stage reaction that involves initial formation of an enzyme-bound acyl-adenylate of P-alanine and subsequent transfer of the P-alanyl moiety to L-histidine. 

The regions of the tRNA molecule teferred to in Chapter 35 (and illustrated in Figure 35-11) now become important. The thymidine-pseudouridine-cyti-dine (T PC) arm is involved in binding of the amino-acyl-tRNA to the ribosomal surface at the site of protein synthesis. The D arm is one of the sites important for the proper recognition of a given tRNA species by its proper aminoacyl-tRNA synthetase. The acceptor arm, located at the 3 -hydroxyl adenosyl terminal, is the site of attachment of the specific amino acid. 

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 ... 

The reaction is catalyzed by the fifth synthetase enzyme-hydroxy acyl hydratase, to produce crotonyl. 

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