Fi oxidation

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). 

Finally, the yeast Yarrowia lipolytica is able to transform ricinoleic acid (12-hydroxy oleic acid) into y-decalactone, a desirable fruity and creamy aroma compound however, the biotransformation pathway involves fi-oxidation and requires the lactonisation at the CIO level. The first step of fi-oxidation in Y. lipolytica is catalysed by five acyl-CoA oxidases (Aox), some of which are long-chain-specific, whereas the short-chain-specific enzymes are also involved in the degradation of the lactone. Genetic constructions have been made to remove these lactone-degrading activities from the yeast strain [49, 50]. A strain displaying only Aox2p activity produced 10 times more lactone than the wild type in 48 h but still showed the same growth behaviour as the wild type. 

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... 

Compart mentation in fi Oxidation Free palmitate is activated to its coenzyme A derivative (palmitoyl-CoA) in the cytosol before it can be oxidized in the mitochondrion. If palmitate and [ CJcoenzyme A are added to a liver homogenate, palmitoyl-CoA isolated from the cytosolic fraction is radioactive, but that isolated from the mitochondrial fraction is not. Explain. 

Sources of H20 IVoduced in fi Oxidation The complete oxidation of palmitoyl-CoA to carbon dioxide and water is represented by the overall equation... 

The first successful catalytic animation of an olefin by transition-metal-catalysed N—H activation was reported for an Ir(I) catalyst and the substrates aniline and norbornene 365498. The reaction involves initial N—FI oxidative addition and olefin insertion 365 - 366, followed by C—FI reductive elimination, yielding the animation product 367. Labelling studies indicated an overall. vyw-addition of N—FI across the exo-face of the norbornene double bond498. In a related study, the animation of non-activated olefins was catalysed by lithium amides and rhodium complexes499. The results suggest different mechanisms, probably with /5-arninoethyl-metal species as intermediates. 

Elaidoyl-CoA acyltransferase I elaidoyl-Carnitine transport elaidoyl-Carnitine acyltransferase II elaidoyl-CoA of fi oxidation (outside) (outside) (inside) (inside)... 

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. 

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. 

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. 

Catabolism of the 14-carbon myristic acid by the fi-oxidation pathway yields seven molecules of acetyl CoA after six passages. 

A Fannitalia group" reported, without details or yields, that both the a- and j3-epoxides derived from testosterone are rearranged by BFs-etherate in benzene to 4-hydroxy-A -3-ketones. Collins (Australia) made a more detailed study in the cholestane series and found that both the a- and the fi-oxide indeed give the hydroxy-A -cholestene-3-one but that they both yield a second product characterized as 5/8-A-norchoIestane-3-one. TTie latter compound evidently comes from an intermediate /3-keto aldehyde, probably by deformylation during chromatography on neutral alumina. 

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. 

Oxide acidity decreases down the group B2O3 (weakly acidic) > AI2O3 > Ga203 > In203 > TI2O (strongly basic), and the -FI oxide is more basic than the -F3 oxide. 

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