Metabolism of unsaturated fatty acids

Metabolism of unsaturated fatty acids is similar to that of the saturated compounds just described, but additional enzymic reactions are necessary. 

Fig. 4. Accessory enzymes required for the metabolism of unsaturated fatty acids.

Between meals, a decreased insulin level and increased levels of insulin counter-regulatory hormones (e.g., glucagon) activate hpolysis, and free fatty acids are transported to tissues bound to serum albumin. Within tissnes, energy is derived from oxidation of fatty acids to acetyl CoA in the pathway of -oxidation. Most of the enzymes involved in fatty acid oxidation are present as 2-3 isoenzymes, which have different but overlapping specificities for the chain length of the fatty acid. Metabolism of unsaturated fatty acids, odd-chain-length fatty acids, and medium-chain-length fatty acids requires variations of this basic pattern. The acetyl CoA produced from fatty acid oxidation is principally oxidized in the TCA cycle or converted to ketone bodies in the liver. 

Mizugaki, M., Kimura, C, Nishimaki, T, Kawaguchi, A., Okuda, S. Yamanaka, H. (1983) /. Biochem., 94, 409-413, Studies on the metabolism of unsaturated fatty acids. XII. Reachon catalyzed by 2,4-dienoyl-CoA reductase of Escherichia coli. 

Oxidative Metabolism of Unsaturated Fatty Acids and Free Radical Formation... 

Jadha, V., B. Singh, D.K. Salunkhe, Metabolism of unsaturated fatty acids in tomato fruit hnoleic and linolenic acid as presursors of hexanol. Plant Cell Physiol., 13, p. 449, 1972. 

Unsaturated fatty acids are probably the most abundant oxidizable endogenous substrates. In the past it was erroneously believed that unsaturated fatty acids are just products of lipid peroxidation. Now, it has been shown that they have dietary origin. Family of unsaturated fatty acids includes linoleic (Ci8), arachidonic (C2o), docosahexaenoic (C22), and other fatty acids containing two, three, four, five, or six double bonds. Some acids can be in vivo converted into others for example, linoleic acid can be metabolized to linolenic and eicosa-trienoic acids [78]. 

Vitamin Ba (pyridoxine, pyridoxal, pyridoxamine) like nicotinic acid is a pyridine derivative. Its phosphorylated form is the coenzyme in enzymes that decarboxylate amino acids, e.g., tyrosine, arginine, glycine, glutamic acid, and dihydroxyphenylalanine. Vitamin B participates as coenzyme in various transaminations. It also functions in the conversion of tryptophan to nicotinic acid and amide. It is generally concerned with protein metabolism, e.g., the vitamin B8 requirement is increased in rats during increased protein intake. Vitamin B6 is also involved in the formation of unsaturated fatty acids. 

An interesting observation is tiiat tile larger tiie amount of unsaturated fatty acids in the diet of hibernating animals, prior to hibernation, tiie lower tile body temperature falls during hibernation. The lower tiie temperature, tiie lower is the metabolic rate, which is important in survival from a prolonged period of hibernation. It is suggested that this is caused by an increase in fluidity of membranes but the mechanism is not known. 

In lipid metabolism, ds-trans isomerism is particularly important. For example, double bonds in natural fatty acids (see p.48) usually have a as configuration. By contrast, unsaturated intermediates of p oxidation have a trans configuration. This makes the breakdown of unsaturated fatty acids more complicated (see p. 166). Light-induced cis-trans isomerization of retinal is of central importance in the visual cycle (see p.358). 

Cyt P450 systems are also involved in many other metabolic processes—e.g., the biosynthesis of steroid hormones (see p. 172), bile acids (see p. 314), and eicosanoids (see p. 390), as well as the formation of unsaturated fatty acids (see p. 409). The liver s reddish-brown color is mainly due to the large amounts of P450 enzymes it contains. 

There may be several mechanisms for these metabolic effects. Unsaturated fatty acids have been shown to directly activate specific enzymes and to induce DNA synthesis and cytokine release from lymphocytes (Karsten et al., 1994). The induction of specific protein synthesis may produce the reduction in glutamine metabolism. The increase in the robustness of the fatty acid-grown hybridomas in agitated cultures could be explained by a high incorporation of the available fatty acids into the cellular phospholipids fraction, which is a major structural component of the outer membrane of the cell (Butler et al., 1999). 

Three major families of unsaturated fatty acids are seen in warm-blooded animals, that is, the n-9, monounsaturated fatty acids (e.g. oleic acid, OA), and the n-6 and n-3, both polyunsaturated fatty acids (PUFAs). However, only the n-6 and n-3 families, derived from LA and ALA, respectively, are EFA. These must be obtained from the diet since mammals lack the desaturase enzymes necessary for the insertion of a double bond in the n-6 and n-3 positions of the fatty acid carbon chain. Fatty acid nomenclature is as follows The first number denotes the number of carbon atoms in the acyl chain and the second refers to the number of unsaturated (double) bonds. This is followed by a symbol n or co and a number that denotes the number of carbon atoms from the methyl terminal of the molecule to the first double bond. Hence, LA is 18 2(n-6), while the more unsaturated ALA is denoted as 18 3(n-3) (Figure 26.1). These fatty acids must be metabolized to their longer chain derivatives before carrying out many of their activities. 

Physically, the membrane may exist in two states the "solid" gel crystalline and the "liquid" fluid crystalline states. For each type of membrane, there is a specific temperature at which one changes into the other. This is the transition temperature (Tc). The Tc is relatively high for membranes containing saturated fatty acids and low for those with unsaturated fatty acids. Thus, bilayers of phosphatidylcholine with two palmitate residues have a Tc = 41°C but that with two oleic acid residues has a Tc = -20°C. The hybrid has a Tc = -5°C. Sphingomyelin bilayer, on the other hand, may have a Tc of close to body temperature. In the gel crystalline state, the hydrophobic tails of phospholipids are ordered, whereas in the fluid crystalline state they are disordered. At body temperature, all eukaryotic membranes appear to be in the liquid crystalline state, and this is caused, in part, by the presence of unsaturated fatty acids and in part by cholesterol. The latter maintains the fatty acid side chains in the disordered state, even below the normal Tc. There is thus no evidence that membranes regulate cellular metabolic activity by changing their physical status from the gel to the fluid state,... 

Vitamin E plays an important role in cell metabolism as an antioxidant for the elimination of reactive oxygen intermediates. Subsequent to intestinal resorption, vitamin E is transported in chylomicrons into the liver, from where it reaches other organs together with VLDL. Vitamin E deficiency is observed in chronic liver diseases caused by alcohol, Wilson s disease, haemochromatosis and abetalipoproteinaemia. In vitamin E deficiency, neurologic disturbances (areflexia, dysbasia, ocular palsy, reduced perception of vibration) occur haemolysis can likewise be induced or become more pronounced due to epoxide formation of unsaturated fatty acids within the erythrocyte membranes. 

Di Augustinem, R.R and J.R. Foutsm. 1969. The effects of unsaturated fatty acids on hepatic microsomal drug metabolism and cytochrome P-450. Biochem.. 115 ... 

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