Oxidative cleavage fatty acids

Oxidation of higher fatty acids was first studied in 1904 by Knoop who fed animals with phenyl-substituted fatty acids and analyzed the products in the urine. He showed that the fatty acid oxidation results in the successive cleavage of two carbon moieties from the carboxyl end. Knoop coined the fatty acid oxidation mechanism as n-oxidation. As has been established by Kennedy and Lehninger in 1948-1949, oxidation of fatty acids occurs in the mitochondria only. Lynen and coworkers... 

Fruebis J, Tsao TS, Javorschi S, et al. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 2001 98 2005-2010. 

Propionyl-CoA is produced as an intermediate of odd chain fatty acid oxidation. Propionyl-CoA is produced by thiolytic cleavage of the five-carbon homolog of acetoacetyl-CoA (see here). 

Fatty Acid Oxidation Spiral. The individual reactions of fatty acid oxidation require the activation of the fatty acid by formation of a thioester with CoA. Subsequent oxidation, dehydration, oxidation, and cleavage all occur only with the acyl CoA compounds (II). The product... 

This discussion will concern only mitochondrial synthesis since this is the major mechanism in heart. Where would control be exerted Since the system has not been dissected, we do not know which is the rate-limiting step. All the equilibria for the enzymes of fatty acid oxidation are close to unity and easily reversed except for the thiolase step, which greatly favors cleavage. Whether or not the synthetic sequence proves to be the reverse of the oxidation sequence, the initial condensation will almost surely prove to be rate-limiting and the step at which control is exerted. As discussed above, Seubert s demonstration of mitochondrial feitty acid synthesis by enzymes of oxidation (Seubert et al., 1957) required an irreversible reductive step, or else the thiolase equilibrium would prevail. 

Fatty acids are susceptible to oxidative attack and cleavage of the fatty acid chain. As oxidation proceeds, the shorter-chain fatty acids break off and produce progressively higher levels of malodorous material. This condition is known as rancidity. Another source of rancidity in fatty foods is the enzymatic hydrolysis of the fatty acid from the glycerol. The effect of this reaction on nutritional aspects of foods is poorly understood andhttie research has been done in the area. 

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] ... 

Fatty acids, both saturated and unsaturated, have found a variety of applications. Brassilic acid (1,11-un-decanedicarboxylic acid [BA]), an important monomer used in many polymer applications, is prepared from erucic acid (Scheme 2), obtained from rapeseed and crambe abyssinica oils by ozonolysis and oxidative cleavage [127]. For example, an oligomer of BA with 1,3-butane diol-lauric acid system is an effective plasticizer for polyvinylchloride. Polyester-based polyurethane elastomers are prepared from BA by condensing with ethylene glycol-propylene glycol. Polyamides based on BA are known to impart moisture resistance. 

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. 

Warwel, S., Sojka, M., and Rusch, M. Synthesis of Dicarboxylic Acids by Transition-Metal Catalyzed Oxidative Cleavage of Terminal-Unsaturated Fatty Acids. 164, 79-98 (1993). Wexle.r, D., Zink, J. I., and Reber, C. Spectroscopic Manifestations of Potential Surface Coupling Along Normal Coordinates in Transition Metal Complexes. 171,173-204 (1994). Willett, P., see Artymiuk, P. J. 174, 73-104 (1995). 

Warwel, S., Sojka, M., and Rusch, M. Synthesis of Dicarboxylic Acids by Transition-Metal Catalyzed Oxidative Cleavage of Terminal-Unsaturated Fatty Acids. 164, 79-98 (1993). 

If the double bond is on an odd carbon, (3 oxidation removes 2-car-bon fragments until it gets to the structure with a 3-cis double bond [R-CH=CH-CH2-C(=0)-SCoA]. A new double bond can t be placed between C-2 and C-3 because there s already a double bond at C-3. In this situation, the activity of an isomerase simply moves the double bond from C-3 to C-2 and at the same time makes sure that the configuration is trans. From this point on, the metabolism is just like normal (3 oxidation (hydration, oxidation, cleavage). If you re counting ATPs, these unsaturated fatty acids produce 2 fewer ATPs for each double bond since there is no FADH2 produced by putting in the double bond (see Fig. 13-6). 

The a-, (3- and y-carotenes, which are found in most plants, are vitamin A provitamins and are converted to vitamin A alcohol (all- ran,v-retinol), which is usually called vitamin Aj (Figure 12.8) by oxidative mid-point cleavage. Retinol and its fatty acid esters are the main forms in which vitamin A is stored in animals and humans, and its oxidation product, 1 1-c/s-retinal (vitamin A, aldehyde), is required for the visual process. 

The -oxidation reaction occurs, for example, when contaminants contain a fatty acid chain. In this case, the reaction proceeds by the stepwise cleavage of two carbon fragments of the fatty acid and ceases when the chain length is two or four carbons (Fig. 15.3). The implementation of P-oxidation requires two protons on both... 

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