Long-chain-fatty-acid-CoA ligase

Long-chain-fatty-acid-coA ligase R223-RXN 0.008890324... 

It also appears that tiaprofenic acid, an NSAID that also undergoes inversion in rats, is not a substrate for purified microsomal rat liver long-chain acyl-CoA synthetase for which R-ibuprofen is a substrate [25]. This data may suggest that metabolic pathways involved in the inversion of tiaprofenic acid and possibly other 2-APA NSAIDs are different from those known for R-ibuprofen. It has been recently reported that in both an in vitro cell-free system and in rat liver homogenates the chiral inversion of ibuprofen was apparent when both CoA and ATP were present however, the NSAID KE-748 was not inverted [26]. To induce hepatic microsomal and outer mitochondrial long-chain fatty acid CoA ligase, rats were treated with clofibric acid [27]. Whereas chiral inversion of ibuprofen was enhanced significantly compared to controls, this was not the case for R(—)-KE-748. 

Knights, K.M. Jones, M.E. Inhibition kinetics of hepatic microsomal long chain fatty acid-CoA ligase by 2-arylpropionic acid non-steroidal antiinflammatory drugs. Biochem. Pharmacol. 1992, 44, 2415-2417. 

The fatty acid in its ionized form is activated in the long-chain-fatty-acid-CoA ligase outer surface of the eukaryotic outer mitochon- q substrates butyrate-CoA... 

In the mucosal cells, long-chain fatty acids are resynthesized by an ATP-dependent ligase [5] to form acyl-CoA and then triacylglycerols (fats see p. 170). The fats are released into the lymph in the form of chylomicrons (see p. 278) and, bypassing the liver, are deposited in the thoracic duct—i. e., the blood system. Cholesterol also follows this route. 

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]. 

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. ... 

Peroxisomal membrane possesses an acyl-CoA ligase activity that is specific for very long-chain fatty acids. Mitochondria apparently cannot activate long-chain fatty acids such as tetracosanoic (24 0) and hexacosanoic (26 0). Peroxisomal carnitine acyltransferases catalyze the transfer of these molecules into peroxisomes, where they are oxidized to form acetyl-CoA and medium-chain acyl-Co A molecules (i.e., those possessing between 6 and 12 carbons). Medium-chain acyl-Co As are further degraded via /3-oxidation within mitochondria. 

Fatty acyl-CoA ligases (specific for short, medium, or long chain fatty acids) catalyze formation of fatty acyl thioester conjugate with coenzyme A (Diagram)... 

We now explore the remarkable process by which a long-chain saturated fatty acid is converted into two-carbon units (acetate), which can be oxidized to C02 and H20 via the tricarboxylic acid cycle and the electron-transport chain. Fatty acids that enter cells are activated to their CoA derivatives by the enzyme acyl-CoA ligase and transported into the mitochondria for /3 oxidation as we discuss later in this chapter. 

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