Fatty acids a-oxidation

Synthesis of 22 6n-3 was not impaired in cell lines with X-ALD (Table 2), suggesting that the adrenoleukodystrophy protein (ALDP), a peroxisomal membrane protein that has been hypothesized to transport very-long-chain saturated fatty acids, does not participate in the retroconversion step of 24 6n-3 to 22 6n-3. The biosynthesis of 22 6n-3 was also normal in fibroblasts from patients with Refsum disease, who have a defect in peroxisomal fatty acid a-oxidation, indicating that a-oxidation does not contribute to 22 6n-3 synthesis. 

Su, X., Han, X., Yang, J., Mancuso, D.J., Chen, J., Bickel, P.E. and Gross, R.W. (2004) Sequential ordered fatty acid a oxidation and D9 desaturation are major determinants of lipid storage and utilization in differentiating adipocytes. Biochemislry 43,5033-5044. 

Baardseth P, Slinde E, Thomassen M. Studies on fatty acid a-oxidation in cucumber. Biochim Biophys Acta 1987 922 170-176. 

The diacids for these polymers are prepared via different processes. A2elaic acid [123-99-9] for nylon-6,9 [28757-63-3] is generally produced from naturally occurring fatty acids via oxidative cleavage of a double bond in the 9-position, eg, from oleic acid [112-80-1] ... 

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. 

In the endoplasmic reticulum of eukaryotic cells, the oxidation of the terminal carbon of a normal fatty acid—a process termed ch-oxidation—can lead to the synthesis of small amounts of dicarboxylic acids (Figure 24.27). Cytochrome P-450, a monooxygenase enzyme that requires NADPH as a coenzyme and uses O, as a substrate, places a hydroxyl group at the terminal carbon. Subsequent oxidation to a carboxyl group produces a dicarboxylic acid. Either end can form an ester linkage to CoA and be subjected to /3-oxidation, producing a... 

Schulz, H., and Knnan, W.-H., 1987. /3-Oxidation of nnsatnrated fatty acids A revised padiway. Trends in Biochemical Sciences 12 403-406. 

Uchicda, Y., Izai, K., Orii, T., Hashimoto, T. (1992). Novel fatty acid p-oxidation enzymes in rat liver mitochondria. II. Purification and properties of enoyl-coenzyme A (CoA) hydratase/3-hy-droxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase trifunctional protein. J. Biol. Chem. 267, 1034-1041. 

Cj5 and Cj7 fatty acids are found particularly in the lipids of ruminants. Dietary odd-carbon fatty acids upon oxidation yield propionate (Chapter 22), which is a substrate for gluconeogenesis in human liver. 

Kawamoto S, C Nozaki, A Tanaka, S Fukui (1978) Fatty acid P-oxidation system in microbodies of -alkane-grown Candida tropicalis. Eur J Biochem 83 609-613. 

The specific behaviour of unsaturated fatty acids under oxidation is determined by the position and the number of double bonds in the fatty acid molecule. The stepwise oxidation of an unsaturated acid to the position of a double bond in it proceeds in a manner similar to that of saturated acid oxidation. If the double bond retains the same configuration (trans-configuration) and position (A2,3) as those of the enoyl-CoA, which is produced during the oxidation of saturated fatty acids, the subsequent oxidation proceeds via conventional route. Otherwise, the oxidation reaction proceeds with the involvement of an accessory enzyme, A3,4-CiS-A2,3jrans-enoyl-CoA isomerase this facilitates the translocation of the double bond to an appropriate position and alters the double-bond configuration from cis to trans. 

In the pathway, the 3HA-CoA is produced from the carbon source by the fatty acid /1-oxidation route so that the 3HA-CoA so formed can be utilized either for the production of a PHA directly or for the production of acetyl-CoA, which results in the formation of 3HA-CoA containing two carbons less than the original 3HA. 3HA-CoA thus formed can similarly be utilized for the production of... 

There is considerable interest in synthesizing copolymers. This is actually possible if organisms are confronted with mixtures of so-called related and unrelated substrates. Copolymers can also be synthesized from unrelated substrates, e.g., from glucose and gluconate. The 3-hydroxydecanoate involved in the polyester is formed by diversion of intermediates from de novo fatty-acid synthesis [41,42]. Related , in this context, refers to substrates for which the monomer in the polymer is always of equal carbon chain length to that of the substrate offered. Starting from related substrates, the synthesis pathway is closely connected to the fatty-acid /1-oxidation cycle [43]. In Pseudomonas oleovor-ans, for example, cultivated on octane, octanol, or octanoic acid, the synthesized medium chain length polyester consists of a major fraction of 3-hydroxyoc-tanoic acid and a minor fraction of 3-hydroxyhexanoic acid. If P. oleovorans is cultivated on nonane, nonanol, or nonanoic acid, the accumulated polyester comprises mainly of 3-hydroxynonanoate [44]. 

Figure 5.15 GALDI mass spectra of (a) linseed oil (35 years airtight storage from THF solution) and (b) linseed oil as in (a) after 2 weeks of natural ageing (from THF solution). Signal groups of free fatty acids, their oxidation products, and monoglycerides (m/z <500) can be distinguished from diglycerides (m/z 500 800), and triglycerides (m/z 800 1000) (see Table 5.7)...

If a fatty acid already has a double bond in it, the scheme by which the fatty acid is oxidized depends on where the double bond ends up after several of the C-2 fragments have been removed by normal p oxidation. With a double bond already present, the enzyme that catalyzes the first step (insertion of the double bond at C-2) gets confused when there is already a double bond at C-2 or at C-3. The fact that the double bonds in unsaturated fatty acids are invariably cis also complicates life since the double bond introduced at C-2 by the desaturating enzyme of p oxidation is a trans double bond. 

Belkner et al. [32] demonstrated that 15-LOX oxidized preferably LDL cholesterol esters. Even in the presence of free linoleic acid, cholesteryl linoleate continued to be a major LOX substrate. It was also found that the depletion of LDL from a-tocopherol has not prevented the LDL oxidation. This is of a special interest in connection with the role of a-tocopherol in LDL oxidation. As the majority of cholesteryl esters is normally buried in the core of a lipoprotein particle and cannot be directly oxidized by LOX, it has been suggested that LDL oxidation might be initiated by a-tocopheryl radical formed during the oxidation of a-tocopherol [33,34]. Correspondingly, it was concluded that the oxidation of LDL by soybean and recombinant human 15-LOXs may occur by two pathways (a) LDL-free fatty acids are oxidized enzymatically with the formation of a-tocopheryl radical, and (b) the a-tocopheryl-mediated oxidation of cholesteryl esters occurs via a nonenzymatic way. Pro and con proofs related to the prooxidant role of a-tocopherol were considered in Chapter 25 in connection with the study of nonenzymatic lipid oxidation and in Chapter 29 dedicated to antioxidants. It should be stressed that comparison of the possible effects of a-tocopherol and nitric oxide on LDL oxidation does not support importance of a-tocopherol prooxidant activity. It should be mentioned that the above data describing the activity of cholesteryl esters in LDL oxidation are in contradiction with some earlier results. Thus in 1988, Sparrow et al. [35] suggested that the 15-LOX-catalyzed oxidation of LDL is accelerated in the presence of phospholipase A2, i.e., the hydrolysis of cholesterol esters is an important step in LDL oxidation. 

Sethi, S., Eastman, A.Y., and Eaton, J.W., 1996, Inhibition of phagocyte-endothelium interaction by oxidized fatty acids A natural anti-inflammatory mechanism J. Lab. Clin. Invest. 128 27-38. 

From the above discussion, it is clear that some tissues synthesise and then release glutamine into the blood and others take up glutamine and use it as a fuel and/or as a nitrogen donor. Hence, glutamine can be considered as a fuel in the blood, alongside glucose and fatty acids. Its oxidation in the Krebs cycle is described in Chapter 9. The... 

Fig. 16.32 Alkane degradation under aerobic conditions, showing incorporation of oxygen from molecular oxygen into the aliphatic compound, producing a fatty acid. Fatty acids are oxidized further by p-oxidation [H] indicates reducing equivalents that are either required or formed in the reaction step. (Bouwer and Zender 1993)...

Most fatty acids are saturated and even-numbered. They are broken down via p-oxidation (see p.l64). In addition, there are special pathways involving degradation of unsaturated fatty acids (A), degradation of fatty acids with an odd number of C atoms (B), a and ro oxidation of fatty acids, and degradation in peroxisomes. 

Polyunsaturated fatty acids are oxidized by enzymatic and nonenzymatic pathways. Nonenzymatic oxidation is a free-radical mediated peroxidation. It is a chain reaction providing a continuous supply of free radicals that initiate further peroxidation. The whole process can be depicted as follows [21] ... 

The 3-OH FAs have had great utility in the determination of LPS levels in indoor air. However, in tissues and body fluids it has been determined that 3-OH FAs are naturally present at low levels as products of mammalian metabolism (mitochondrial fatty acid p oxidation). Due to this background GC-MS/MS for 3-OH FAs is not recommended as a general marker to determine trace LPS levels in clinical samples [14]. However, in certain situations the assessment of 3-OH FAs has been successfully used, for example, in the diagnosis of chronic peridontitis [15]. There is great potential for the utility of 3-OH FAs as markers for LPS contamination in pharmaceutical products, where often the background matrix would be anticipated to be much less complex. 

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