0-Oxidation pathway

The hver microsomal dmg-metabolizing system is of particular importance. This oxidative pathway is mediated by isozymes of the cytochrome family (Fig. 4). At least ten enzyme families exist to accommodate the abiUty of humans to handle many foreign molecules (21). 

Respiratory, or oxidative, metaboHsm produces more energy than fermentation. Complete oxidation of one mol of glucose to carbon dioxide and water may produce up to 36 mol ATP in the tricarboxyHc acid (TCA) cycle or related oxidative pathways. More substrates can be respired than fermented, including pentoses (eg, by Candida species), ethanol (eg, by Saccharomjces), methanol (eg, by Hansenu/a species), and alkanes (eg, by Saccharomjces lipoljticd). 

All of the other enzymes of the /3-oxidation pathway are located in the mitochondrial matrix. Short-chain fatty acids, as already mentioned, are transported into the matrix as free acids and form the acyl-CoA derivatives there. However, long-chain fatty acyl-CoA derivatives cannot be transported into the matrix directly. These long-chain derivatives must first be converted to acylearnitine derivatives, as shown in Figure 24.9. Carnitine acyltransferase I, located on the outer side of the inner mitochondrial membrane, catalyzes the formation of... 

FIGURE 24.23 )3-Oxidation of unsaturated fatty acids. In the case of oleoyl-CoA, three /3-oxidation cycles produce three molecules of acetyl-CoA and leave m-AAdodecenoyl-CoA. Rearrangement of enoyl-CoA isomerase gives the tran.s-A species, which then proceeds normally through the /3-oxidation pathway. 

Polyunsaturated fatty acids pose a slightly more complicated situation for the cell. Consider, for example, the case of linoleic acid shown in Figure 24.24. As with oleic acid, /3-oxidation proceeds through three cycles, and enoyl-CoA isomerase converts the cA-A double bond to a trans-b double bond to permit one more round of /3-oxidation. What results this time, however, is a cA-A enoyl-CoA, which is converted normally by acyl-CoA dehydrogenase to a trans-b, cis-b species. This, however, is a poor substrate for the enoyl-CoA hydratase. This problem is solved by 2,4-dienoyl-CoA reductase, the product of which depends on the organism. The mammalian form of this enzyme produces a trans-b enoyl product, as shown in Figure 24.24, which can be converted by an enoyl-CoA isomerase to the trans-b enoyl-CoA, which can then proceed normally through the /3-oxidation pathway. Escherichia coli possesses a... 

FIGURE 24.24 The oxidation pathway for polyunsaturated fatty adds, illustrated for linoleic add. Three cycles of /3-oxidation on linoleoyl-CoA yield the cis-A, d.s-A intermediate, which is converted to a tran.s-A, cis-A intermediate. An additional round of /S-oxi-dation gives d.s-A enoyl-CoA, which is oxidized to the trans-A, d.s-A species by acyl-CoA dehydrogenase. The subsequent action of 2,4-dienoyl-CoA reductase yields the trans-A product, which is converted by enoyl-CoA isomerase to the tran.s-A form. Normal /S-oxida-tion then produces five molecules of acetyl-CoA. 

The a-oxidation pathway is defective in Refsum s disease, an inherited metabolic disorder that results in defective night vision, tremors, and other neurologic abnormalities. These symptoms are caused by accumulation of phytanic acid in the body. Treatment of Refsum s disease requires a diet free of chloro-... 

Step 1 of Figure 29.3 Introduction of a Double Bond The /3-oxidation pathway begins when a fait)7 acid forms a thioester with coenzyme A to give a fatty acyl Co A. Two hydrogen atoms are then removed from C2 and C3 of the fatty acyl CoA by one of a family of acyl-CoA dehydrogenases to yield an a,/3-unsaturated acyl CoA. This kind of oxidation—the introduction of a conjugated double bond into a carbonyl compound—occurs frequently jn biochemical pathways and usually involves the coenzyme flavin adenine dinucleotide (FAD). Reduced FADH2 is the by-product. 

The four steps of the /3-oxidation pathway, resulting in the cleavage of an acetyl group from the end of the fatty-acid chain. The key chain-shortening step is a retro-Claisen reaction of a /3-keto thioester. Individual steps are explained in the text. 

The retro-Claisen reaction occurs by initial nucleophilic addition of a cysteine -SH group on the enzyme to the keto group of the /3-ketoacyl CoA to yield an alkoxide ion intermediate. Cleavage of the C2-C3 bond then follows, with expulsion of an acetyl CoA enolate ion. Protonation of the enolate ion gives acetyl CoA, and the enzyme-bound acyl group undergoes nucleophilic acyl substitution by reaction with a molecule of coenzyme A. The chain-shortened acyl CoA that results then enters another round of tire /3-oxidation pathway for further degradation. 

Look al the catabolism of my fistic acid shown in Figure 29.4 to see the overall results of the /3-oxidation pathway. The first passage converts the 14-carbon myristoyl CoA into the 12-carbon lauroyl CoA plus acetyl CoA, the second passage converts lauroyl CoA into the 10-carbon caproyl CoA plus acetyl CoA, the third passage converts caproyl CoA into the 8-carbon capryloyl CoA, and so on. Note that the final passage produces two molecules of acetyl CoA because the precursor has four carbons. 

Figure 29.4 Catabolism of the 14-carbon myristicacid by the 0-oxidation pathway yields seven molecules of acetyl CoA after six passages.

Problem 29.2 Write the equations for the remaining passages of the jS-oxidation pathway following those shown in Figure 29.4. 

As a rule, the anabolic pathway by which a substance is made is not the reverse of the catabolic pathway by which the same substance is degraded. The two paths must differ in some respects for both to be energetically favorable. Thus, the y3-oxidation pathway for converting fatty acids into acetyl CoA and the biosynthesis of fatty acids from acetyl CoA are related but are not exact opposites. Differences include the identity of the acvl-group carrier, the stereochemistry of the / -hydroxyacyl reaction intermediate, and the identity of the redox coenzyme. FAD is used to introduce a double bond in jS-oxidalion, while NADPH is used to reduce the double bond in fatty-acid biosynthesis. 

Write the equation for the final step in the /3-oxidation pathway of any fatty acid with an even number of carbon atoms. 

Oxidation pathway (Section 29.3) The metabolic pathway for degrading fatty acids. 

Michael reactions and, 895 Beta-keto ester, 851 alkylation of, 859-860 cyclic, 892-893 decarboxylation of, 857, 860 Michael reactions and. 895 pKd of, 852 synthesis of, 892-893 Beta-lactam antibiotics, 824-825 Beta oxidation pathway, 1133-1137 mechanism of, 1133-1136 Beta-pleated sheet (protein), 1038 molecular model of, 1039 secondary protein structure and, 1038-1039 Betaine, 720 Bextra. structure of, 544 BHA, synthesis of, 629 BHT, synthesis of. 629 Bicycloalkane. 129 Bijvoet. J. M., 299 Bimolecular, 363... 

The chemical engineering approach began with an analysis of the biochemistry of platelet metabolism. Like many cells, platelets consume glucose by two pathways, an oxidative pathway and an anaerobic pathway. The oxidative pathway produces carbon dioxide, which makes the solution containing the platelets more acidic (lower pH) and promotes anaerobic metabolism. This second metabolic pathway produces large amounts of lactic acid, further lowering pH. The drop in pH from both pathways kills the platelets. 

LIF has been used in a multitude of studies to measure the concentrations of some important radicals, most frequently of OH, CH, and NO. While OH is an important contributor to the fuel degradation and oxidation pathways and an indicator of hot areas in flames, CH has often been used to trace the flame front location, whereas the direct investigation of NO formation is of importance with regard to NO, being a regulated air toxic. Species including other elements, such as sulfur, phosphorus, alkali, etc., can be detected by LIF in combustion systems, and often, an indication of their presence may already be a useful result, even if quantification is not possible. 

It was first assumed that the oxidant was H2O2. However, since traces of Fe-cations are present, a Fenton s type oxidation pathway, based on OH radicals, is more likely taking place. 

Generally, NAD-linked dehydrogenases catalyze ox-idoreduction reactions in the oxidative pathways of metabolism, particularly in glycolysis, in the citric acid cycle, and in the respiratory chain of mitochondria. NADP-linked dehydrogenases are found characteristically in reductive syntheses, as in the extramitochon-drial pathway of fatty acid synthesis and steroid synthesis—and also in the pentose phosphate pathway. 

OXIDATION OF UNSATURATED FATTY ACIDS OCCURS BY A MODIFIED P-OXIDATION PATHWAY... 

After uptake by the liver, free fatty acids are either P Oxidized to COj or ketone bodies or esterified to triacylglycerol and phospholipid. There is regulation of entry of fatty acids into the oxidative pathway by carnitine palmitojdtransferase-I (CPT-I), and the remainder of the fatty acid uptake is esterified. CPT-I activity is... 

The corrosion of iron occurs particularly rapidly when an aqueous solution is present. This is because water that contains ions provides an oxidation pathway with an activation energy that is much lower than the activation energy for the direct reaction of iron with oxygen gas. As illustrated schematically in Figure 19-21. oxidation and reduction occur at different locations on the metal surface. In the absence of dissolved ions to act as charge carriers, a complete electrical circuit is missing, so the redox reaction is slow, hi contrast, when dissolved ions are present, such as in salt water and acidic water, corrosion can be quite rapid. 

Jeftic L, RN Adams (1970) Electrochemical oxidation pathways of benzo(a)pyrene. J Am Chem Soc 92 1332-1337. 

The degradation of 11,12-methyleneoctadecanoate is carried out in Tetrahymena pyri-formis by a modified p-oxidation pathway with the formation of propionate and acetate (Figure 7.34a) (Tipton and Al-Shather 1974). 

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