Fatty acids fi-oxidation

Certain CoA thioester using enzymes catalyze reactions at the fS-carbon or other carbons of the acyl group more distant from the thioester functionality. The fatty acid fi-oxidation cycle provides some examples (Fig. 3). Fatty acids 7 enter the cycle by initial conversion to the CoA ester 8, which is then oxidized to the a,P-unsaturated thioester 9 by a flavin-dependent enzyme. Addition of water to the double bond to form the fi-hydroxy thioester 10 is catalyzed by the enzyme crotonase, which is the centerpiece of the crotonase superfamily of enzymes that catalyze related reactions (37), which is followed by oxidation of the alcohol to form the fi-keto thioester 11. A retro-Claisen reaction catalyzed by thiolase forms acetyl-CoA 12 along with a new acyl-CoA 13 having a carbon chain two carbons shorter than in the initial or previous cycle. 

Biosynthesis of22 6n-3 in Peroxisomal Fatty Acid fi-Oxidation Enzyme Deficiency... 

The aromas associated widi very fi esh fish are usually mild, delicate and fi esh (53,54), and generally described as green (hexanal), melon-like ((E,Z)-3,6-nonadienal), iodine-like (bromophenols). Fresh fish and seafood aromas are due to volatile carbonyls and derive fi om lipoxygenase catalyzed oxidation of polyunsaturated fatty acids. The oxidation of Eicosapentaenoic acid (C20 5) leads to C5 to C9 alcohols, aldehydes, ketones and hydrocarbons. The formation of methyl mercaptan, dimethyl sulfide and dimethyl disulfide in fi esh fish at the time of harvest has been reported by Shiomi et al. (55). Although these compounds are usually associated with fish deterioration, they contribute to the fi esh aroma ch cter at low concentrations. For instance, dimethyl sulfide is... 

By permanganate oxidation long side chains are broken down to carboxyl groups attached to the ring. The biological degradation of oj-aryl-fatty acids proceeds in accordance with the fi-oxidation rule (F. Knoop). 

A second important difference between mitochondrial and peroxisomal fi oxidation in mammals is in the specificity for fatty acyl-CoAs the peroxisomal system is much more active on very-long-chain fatty acids such as hexacosanoic acid (26 0) and on branched-chain fatty acids such as phytanic acid and pristanic acid (see Fig. 17-17). These less-common fatty acids are obtained in the diet from dairy products, the fat of ruminant animals, meat, and fish. Their catabolism in the peroxisome involves several auxiliary enzymes unique to this organelle. The inability to oxidize these compounds is responsible for several serious human diseases. Individuals with Zellweger syndrome are unable to make peroxisomes and therefore lack all the metabolism unique to that organelle. In X-linked adrenoleukodystrophy (XALD), peroxisomes fail to... 

Carnitine (3-hydroxy,4-Al-trimethylaminobutyric acid) has a central role in the transport of fatty acids across the mitochondrial membrane for fi -oxidation. At the outer face of the outer mitochondrial membrane, carnitine acyltransferase I catalyzes the reaction shown in Figure 14.1, the transfer of fatty acids from coenzyme A (CoA) to form acyl carnitine esters that cross into the mitochondrial matrix. At the inner face of the inner mitochondrial membrane, carnitine acyltransferase II catalyzes the reverse reaction. 

Arachidonic acid is not the only polyunsaturated fatty acid that can be oxidized to generate IsoPs. The basic requirement for cyclization to occur is the presence of at least three double bonds. F-ring IsoPs have been shown to be generated from the peroxidation of linolenic acid [CI8 3, i -3, Fi-IsoPs] (21), EPA [C20 5, w-3, Fs-IsoPs] (22), and DHA [C22 6, m-3, F4-IS0PS... 

Very long chain fatty acids are initially oxidized in the peroxisome where the initial oxidation step is catalyzed by acyl-CoA oxidase and the subsequent steps in fS-oxidation are catalyzed by a multi-enzyme complex with hydratase, dehydo-genase, and thiolase activities. Unsaturated fatty acids require additional enzymatic activities, including enoyl-CoA isomerase and dienoyl-CoA reductase. Readers are directed to Vance and Vance (2) for additional details regarding fi-oxidation, including the details of the metabolic reactions. 

Deterioration of food lipids by fi ee radical chain reaction and lipid peroxidation is a major problem for food manufacturers. The main route of deterioration of vegetable oils is rancidity deriving fi-om the oxidation taking place at the insaturation sites of the fatty acids in the triglyceride molecules. In general the higher the number of double bonds, the easier is... 

The four steps of the -oxidation pathway, resulting in the cleavage of an acetyl group from the end of the fatty acid chain. The key chainshortening step is a retro-Claisen reaction of a fi keto thiol ester. 

To explain these data we developed the hypothesis that laetisaric acid and active analogs are metabolized by sensitive fungi, such as P. ultimum, via common fi-oxidation to an active 2-hydroxy twelve carbon fatty acid. In the case of laetisaric acid the metabolic product is 2-hydroxydodecadienoic acid. This a-hydroxy compound is apparently not further metabolized by fi-oxidation and accumulates as the ultimate allelopathic agent. 

FIGURE 17-11 Oxidation of propionyl-CoA produced by fi oxidation of odd-number fatty acids. The sequence involves the carboxy-lation of propionyl-CoA to D-methylmalonyl-CoA and conversion of the latter to succinyl-CoA. This conversion requires epimerization of D- to L-methylmalonyl-CoA, follow/ed by a remarkable reaction in which substituents on adjacent carbon atoms exchange positions (see Box 17-2). 

Parallel Pathways for Amino Acid and Fatty Acid Degradation The carbon skeleton of leucine is degraded by a series of reactions closely analogous to those of the citric acid cycle and fi oxidation. For each reaction, (a) through (0, indicate its type, provide an analogous example from the citric acid cycle or )3-oxidationpathway (where possible), and note any necessary cofactors. 

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