Fatty acid oxidase

Several enzymes, known collectively as fatty acid oxidase, are found in the mitochondrial matrix or inner membrane adjacent to the respiratory chain. These catalyze the oxidation of acyl-CoA to acetyl-CoA, the system being coupled with the phosphorylation of ADP to ATP (Figure 22-3). 

In 1976 Lazarow and deDuve [5] showed that peroxisomes contain a second p-oxidation system for fatty acids, and they showed that this system is induced in the hver of rats fed the hypohpemic drug clofibrate. The fatty acid oxidase of the peroxisomes has hydrogen peroxide as reaction product. The observations of Lazarow and deDuve led us to test whether the peroxisomes are active in the oxidation of the very long-chain fatty acids and whether the adaptation to their presence in the diet was caused by changed peroxisomal activity. 

As discussed previously, the fatty acid oxidase of cells is associated with mitochondria. Soluble systems prepared from mitochondria would be expected to reveal the need for cofactors that are already present in the mitochondrion as an integral part of its organization. 

Lipoxygenases (LOXs) represent a group of polyunsaturated fatty acid oxidases that are apparently ublqultlous In eukaryotic organisms. There are a growing number of reports of the presence of this enzyme In various human and other animal tissues. The list of plants containing active LOXs also continues to expand. 

The properties of a lipoxidase from peas have been studied by Siddiqi and Tappel (660). Because their preparation possesses no fatty acid oxidase or fatty acid dehydrogenase activity and oxidizes linoleate but not oleate, it behaves like a true lipoxidase. The products of linoleate oxidation contain carbonyl groups although a correlation of the intenfflty of absorption with peroxide concentration suggests that the initial products of pea lipoxidase action are totally conjugated hydroperoxides. These appear to be very unstable under the conditions of formation, undergoing scission and polymerization to form aldehydes and trienes, detected by the presence of an absorption band at 280 m/t. 

There a number of cases other than those of dihydroxyfumaric acid oxidase and tryptophan oxidase in which peroxidases appear to play the part of oxidases. These include indolylacetic acid oxidase and the related indolylpropionic and indolylbutyric acid oxidases (285, 415,416,618,733,777), the oxidase of oxalic, oxalacetic, ketomalonic, and dihydroxytartaric acids (414), of phenylacetaldehyde (413) and saturated fatty acid oxidase (711). 

Aldehyde oxidase milk aldehydes fatty acid approx. 7 0... 

Although /3-oxidation is universally important, there are some instances in which it cannot operate effectively. For example, branched-chain fatty acids with alkyl branches at odd-numbered carbons are not effective substrates for /3-oxidation. For such species, a-oxidation is a useful alternative. Consider phy-tol, a breakdown product of chlorophyll that occurs in the fat of ruminant animals such as sheep and cows and also in dairy products. Ruminants oxidize phytol to phytanic acid, and digestion of phytanic acid in dairy products is thus an important dietary consideration for humans. The methyl group at C-3 will block /3-oxidation, but, as shown in Figure 24.26, phytanic acid a-hydroxylase places an —OFI group at the a-carbon, and phytanic acid a-oxidase decar-boxylates it to yield pristanie add. The CoA ester of this metabolite can undergo /3-oxidation in the normal manner. The terminal product, isobutyryl-CoA, can be sent into the TCA cycle by conversion to succinyl-CoA. 

FIGURE 24.26 Branched-chain fatty acids are oxidized by o -oxidation, as shown for phytanic acid. The product of the phytanic acid oxidase, pristanic acid, is a suitable substrate for normal /3-oxidation. Isobutyryl-CoA and propionyl-CoA can both be converted to suc-cinyl-CoA, which can enter the TCA cycle. 

These include the mitochondrial respiratory chain, key enzymes in fatty acid and amino acid oxidation, and the citric acid cycle. Reoxidation of the reduced flavin in oxygenases and mixed-function oxidases proceeds by way of formation of the flavin radical and flavin hydroperoxide, with the intermediate generation of superoxide and perhydroxyl radicals and hydrogen peroxide. Because of this, flavin oxidases make a significant contribution to the total oxidant stress of the body. 

Fig.i General biosynthetic pathways for the production of alcohol, aldehyde, and acetate ester pheromone components in female moths. Top production of saturated fatty acids. Middle production of monounsaturated fatty acids and limited chain shortening produces intermediate compounds that can be reduced to an alcohol. Aldehyde and acetate ester pheromones are produced by an oxidase and acetyl-transferase, respectively. Bottom biosynthetic pathway for the production of the acetate ester pheromone components in the cabbage looper moth, Trichoplusia ni. The CoA derivatives are reduced and acetylated to form the acetate esters. Additional pheromone components include 12 OAc and ll-12 OAc... 

Figure 9. Stereochemical differences between fatty acid hydroperoxide- and mixed-function oxidase-dependent oxidation of ( ) -BP-7,8-dihydrodiol.

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