Fatty acyl CoA synthetase

Pantothenic acid CoA i Fatty acid synthase Fatty acyl CoA synthetase Pyruvate dehydrogenase ci-Ketoglutarate dehydrogenase Fatty acid metabolism PDH TCA cycle Rare... 

When fatty adds are used in metabolism, they are first activated by attaching coenzyme A (CoA) fatty acyl CoA synthetase catalyzes this activation step. The product is genetically referred to as a fatty acyl CoA or sometimes just acyl CoA. Specific examples would be acetyl CoA with a 2-carbon acyl group, or palmitoyl CoA with a 16-carbon acyl group. 

Long-chain fatty acids must be activated and transported into the mitochondria. Fatty acyl CoA synthetase, on the outer mitochondrial membrane, activates the fatty adds by attaching CoA. The fetty acyl portion is then transferred onto carnitine by carnitine aqdtransferase-I for transport into the mitochondria. The sequence of events is shown in Figure 1-16-2 and indudes the following steps ... 

Long-chain fatty acyl-CoA synthetase [EC 6.2.1.3] catalyzes the reaction of ATP with a long-chain carboxylic acid and coenzyme A to produce an acyl-CoA, AMP, and pyrophosphate. While utilizing a wide range of long-chain saturated and unsaturated fatty acids as substrates, enzymes from different tissues vary in their specificity. 

LEUCYL-tRNA SYNTHETASE LONG-CHAIN FATTY ACYL-CoA SYNTHETASE LUCIEERASE... 

After a LCFA enters a cell, it is converted to the CoA derivative by long-chain fatty acyl CoA synthetase (thiokinase) in the cytosol (see p. 174). Because 0-oxidation occurs in the mitochondrial matrix, the fatty acid must be transported across the mitochon drial inner membrane. Therefore, a specialized carrier transports the long-chain acyl group from the cytosol into the mitochondrial matrix. This carrier is carnitine, and the transport process is called the carnitine shuttle (Figure 16.16). 

The mixture of lipids moves to the endoplasmic reticulum, where fatty acyl CoA synthetase converts free fatty acids into their activated CoA derivatives. Fatty acyl CoAs are then used to produce triacylglycerols, cholesteryl esters, and phospholipids. These, together with the fat-soluble vitamins (A, D, E, and K) and a single protein (apolipoprotein B-48), form a chylomicron, which is secreted into the lymphatic system and carried to the blood. 

The activating enzyme occurs in the mitochondria and belongs to a class of enzymes known as the ATP-dependent acid CoA ligases (AMP) but has also been known as acyl CoA synthetase and acid-activating enzyme. It appears to be identical to the intermediate chain length fatty acyl-CoA-synthetase. 

Fatty acids are utilized as fuels by most tissues, although the brain, red and white blood cells, the retina, and adrenal medulla are important exceptions. Catabolism of fatty acids requires extramitochondrial activation, transport into mitochondria, and then oxidation via the /3-oxidative pathway. The initial step is catalyzed by fatty acyl-CoA synthetase (also called thiokinase and fatty acyl-CoA ligase), as shown in Equation (19.5). The product, fatty acyl-CoA, then exchanges the CoA for carnitine, as shown in Equation (19.6) ... 

Figure 19.5 Movement of fatty adds across inner mitochondrial membrane. The enzymes involved are designated as follows (1) fatty acyl-CoA synthetase (2) palmitoyl-CoA-camitine acyltransferase on the cytosol side of the inner mitochondrial membrane and (3) the same enzyme on the mitochondrial matrix side of the membrane.

Fatty acid oxidation is a multistep process requiring orchestration of reactions in the cytoplasm and mitochondria (Fig. 9-1). Free fatty acids enter the cell and are activated to their coenzyme A (CoA) thioesters in the reaction catalyzed by fatty acyl-CoA synthetase ... 

Long chain fatty acids are are bound to Fatty acid binding protein for transport within the cytosol. They are impermeable to the inner mitochondrial membrane. They are thus esterified in the cytosol by microsomal Fatty acyl CoA synthetase in a reaction identical to the one shown above. Again the reaction is driven by the hydrolysis of pyrophosphate. The enzyme involves an acyl AMP intermediate ... 

EC 6.2.1.1 Short-chain fatty acyl-CoA synthetase (ACSS) EC 6.2.1.2 Medium-chain acyl-CoA synthetase EC 6.2.1.3 Long-chain acyl-CoA synthetase [ACSL)... 

FIREFLY hVClFERASE AND DROSOPHILA CG6178 GENE PRODUCT ARE FATTY ACYL-COA SYNTHETASES... 

In firefly luciferase reaction, the luminescence activity is enhanced by addition of Coenzyme A (CoA) and this phenomenon is explained by release of product inhibition. Also, firefly luciferase shows the sequence similarity to mammalian fatty acyl-CoA synthetase (AcCoAS) and plant 4-coumarate CoA ligase (4CL). They are classified as an adenylation enzyme for synthesizing acyl-CoA derivatives fi om carboxylic acid compounds in the presence of CoA, ATP and Mg (Scheme 1). Furthermore, it was reported that the luminescence activity of firefly luciferase is inhibited competitively by various long-chain fatty acids. We have determined that firefly luciferase is a bi-functional enzyme, catalyzing both the luminescence reaction and fatty acyl-CoA synthetic reaction. ... 

Oba Y, Ojika M, Inouye S. Firefly luciferase is a bifunctional enzyme ATP-dependent monooxygenase and a long chain fatty acyl-CoA synthetase. FEBS Lett 2003 540 251-4. 

Fig. 23.1. Overview of mitochondrial long-chain fatty acid metabolism. (1) Fatty acid binding proteins (FaBP) transport fatty acids across the plasma membrane and bind them in the cytosol. (2) Fatty acyl CoA synthetase activates fatty acids to fatly acyl CoAs. (3) Carnitine transports the activated fatty acyl group into mitochondria. (4) p-oxidation generates NADH, FAD(2H), and acetyl CoA (5) In the liver, acetyl CoA is converted to ketone bodies...

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