Fatty acid odd carbon number

One hundred and eighty-one molecular species of TGs have been identified 79 of them were saturated, 44 monounsaturated, and 58 polyunsaturated. The majority of the unsaturated TGs (61) contained only one unsaturated fatty acid, 41 contained two, and 5 had all three fatty acids unsaturated. Furthermore, ten TGs that contained linear or branched odd-carbon-number fatty acids have been identified. In Table 6, identified species are mentioned with retention times and peak numbers corresponding to the chromatogram in Fig. 43. 

Their study agrees with the Myher et al. (130) estimation in the identification of TGs with odd-carbon-number fatty acids (CN = 15 and 17), either branched or linear. However, they have been able to differentiate between iso and anteiso isomers not only in the GLC analysis of fatty acids but also in TG estimation. Tridecanoic and nonadecanoic acids were identified by GLC but were not included in TG estimation due to their low amounts in whole milk fat content. 

Table 2-2 Saturated Even- and Odd-Carbon Numbered Fatty Acids...

The propionyl CoA to succinyl CoA pathway is a major anaplerotic route for the TCA cycle and is used in the degradation of valine, isoleucine, and a number of other compounds. In the liver, this route provides precursors of oxaloacetate, which is converted to glucose. Thus, this small proportion of the odd-carbon-number fatty acid chain can be converted to glucose. In contrast, the acetyl CoA formed from (3-oxidation of even-chain-number fatty acids in the liver either enters the TCA cycle, where it is principally oxidized to CO2, or is converted to ketone bodies. 

The final unique stage in the metabolism of L-isoleucine involves the cleavage of 2-methylacetoacetyl-CoA to acetyl-CoA and propionyl-CoA (Section 10.4). The propionyl-CoA is further metabolized to methylmalonyl-CoA by a biotin-dependent carboxylase and subsequently via succinyl-CoA into the tricarboxylic acid cycle. L-Valine is also metabolized ultimately to methylmalonyl-CoA (Section 10.4), and thus these two branched-chain amino acids form the major precursors of propionyl-CoA and methylmalonyl-CoA. Other precursors of propionyl-CoA include methionine, threonine, odd-carbon-number fatty acids and cholesterol. The methyhnalonyl-CoA produced by propionyl-CoA carboxylase occurs as the D(5)-enantiomer and is racemized to the L(/ )-enantiomer by methylmalonyl-CoA racemase. l(/ )-Methylmalonyl-CoA is then metabolized to succinyl-CoA by a vitamin B12-dependent mutase prior to introduction of the modified molecule into the tricarboxylic acid cycle. 

The identity of propionic acidaemia with ketotic hyperglycinaemia was confirmed by Gompertz et al. (1970), who reported the second case of propionic acidaemia, a male child of first-cousin Pakistani parents, and correlated the clinical and biochemical observations of propionic acidaemia, hyperglycinaemia, accumulation of odd-carbon-number fatty acids (Ci5 0, Ci7 0, Ci7 1), and butanonuria, with an activity of propionyl-CoA carboxylase in liver mitochondria in vitro of only 10 per cent of that of control. The child died at 8 days of age. 

Propionyl-CoA is the key intermediate in the formation of the majority of the abnormal urinary metabolites observed in propionic acidaemia and is also responsible for the accumulation of odd-carbon-number fatty acids and abnormal triglycerides and lipids in the disease by competition with acetyl-CoA in fatty acid biosynthesis. The metabolite may also inhibit other enzyme systems, particularly in mitochondria, giving rise to other symptoms. Inhibition of A -acetylglutamate synthetase has been used to explain the hyper-ammonaemia that is frequently observed in patients with propionic acidaemia (Coude et al., 1979), sometimes occurring as the major presenting biochemical abnormality (Harris et ai, 1980). Inhibition of other enzyme systems and of mitochondrial function by propionyl-CoA may well also be responsible for the occasional occurrence of hypoglycaemia in the diseases. Propionyl-CoA accumulation is also Important in the biochemical and clinical presentation of patients with methylmalonic aciduria, the disease described in the next section (11.2). 

The final step in fatty acid catabolism involves the attack of a molecule of coenzyme A at the 3fatty acid, resulting in the discharge of a two-carbon imit (acetyl group). The sole breakdown product of even-carbon-numbered fatty acids, such as palmitic add, is acetyl-CoA. A small fraction of the fatty adds encoimtered in the diet have an odd number of carbons. The catabolism of these fatty acids yields a number of molecules of acetyl-CoA plus one molecule of propionyl-CoA. 

In the previous sections, all described complexes were formed between the aromatic compounds and surfactant molecules which have alkyl groups with even-number carbon atoms, such as hexadecyl, tetradecyl, dodecyl and decyl groups. These even-carbon-chain surfactants are utilized widely in vitro and are commercially available. However, there are several odd-carbon-chain fatty acids in vivo, although most fatty acids have even-carbon chains. The former acids are digested in the rumen of ruminants. The odd-carbon-chain surfactants were synthesized from the corresponding odd-carbon-chain fatty acids [56-58]. Two kinds of surfactant molecules with alkyl groups of odd-number carbon atoms, pentadecyl- and tridecyltrimethylammonium bromides (PTAB and TTAB, respectively), were prepared and their complexes with biphenyl were formed. The crystals were obtained from aqueous solutions. 

Odd-numbered fatty acids do occur naturally with carbon numbers between 3 and 19. Those with carbon numbers 15 to 19 are present in large amounts in certain species of fish and bacteria. Even-numbered fatty acids, 4 to 10, are mainly found in milk and butter fats. 

Most of our fat intake will consist of fatty acids with an even number of carbon atoms, but not all dietary fatty acids nor all those synthesized in the liver are saturated. A variable, but probably not inconsiderable, proportion of dietary fatty acids are unsaturated, partly perhaps because a high intake of unsaturated fat is recommended to help reduce the risk for diseases of the heart and vascular system. Unsaturated and odd-numbered fatty acids pose particular chemical problems to the 3-oxidation pathway and additional enzymes are required for their metabolism. 

Figure 7.18 TCA entry of terminal carbon atoms of odd-numbered fatty acids...

Although most naturally occurring lipids contain fatty acids with an even number of carbon atoms, fatty acids with an odd number of carbons are common in the lipids of many plants and some marine organisms. Cattle and other ruminant animals form large amounts of the three-carbon propionate (CH3—CH2—COO ) during fermentation of carbohydrates in the rumen. The propionate is absorbed into the blood and oxidized by the liver and other tissues. And small quantities of propionate are added as a mold inhibitor to some breads and cereals, thus entering the human diet. 

Long-chain odd-number fatty acids are oxidized in the same pathway as the even-number acids, beginning at the carboxyl end of the chain. However, the substrate for the last pass through the jS-oxidation sequence is a fatty acyl-CoA with a five-carbon fatty acid. When this is oxidized and cleaved, the products are acetyl-CoAand propionyl-CoA. The acetyl-CoA can be oxidized in the citric acid cycle, of course, but propionyl-CoA enters a different pathway involving three enzymes. 

RGURE 17-11 Oxidation of propionyl-CoA produced by ft oxidation of odd-number fatty acids Hie 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, followed by a remarkable reaction in which substituents on adjacent carbon atoms exchange positions (see Box 17-2). 

New (de novo) fatty acids are synthesized from two-carbon acetyl units produced during metabolism. Two enzyme complexes, acetyl-coenzyme A carboxylase and fatty acid synthetase, work in concert to build up fatty acid chains, two carbons at a time, until released by the complex. The primer in plants and animals is essentially a two-carbon acetyl group and the fatty acid chains have even numbers of carbons. If the primer is a three-carbon propionate group, odd-number carbon chains result. Odd-number fatty acids are common in microbial lipids and also are synthesized de novo from propionic VFA by rumen bacteria and deposited in adipose tissue. The length of the fatty acid synthesized depends on the tissue. Palmitic acid is produced in the liver and adipose tissue, and shorter-chain fatty acids are also produced in the mammary glands (49). 

The p-oxidation pathway accomplishes the complete degradation of saturated fatty acids having an even number of carbon atoms, fatty acids have such structures because of their mode of synthesis (p. 636). However, not all fatty acids are so simple. The oxidation of fatty acids containing double bonds requires additional steps, as does the oxidation of fatty acids containing an odd number of carbon atoms. 

Scheme 1.3 The alternating toxicity of ft)-fluorocarboxylic acids can be explained by the oxidative metabolism of fatty acids in Cj units. Only if the number of carbon atoms is even the final oxidation product is the highly toxic fluoroacetate [36]. Odd-membered -fluoro fatty acids are metabolized to the less toxic 3-fluoropropionate.

Fatty acids with odd numbers of carbon atoms are not as frequently encountered in nature as are the ones with even numbers of carbon atoms. Odd-numbered fatty acids also undergo P-oxidation (Figure 21.8). The last cycle of P-oxidation produces one molecule of propionyl-GoA. An enzymatic pathway exists to convert propionyl-GoA to succinyl-GoA, which then enters the citric acid cycle. In this pathway, propionyl-GoA is hrst carboxylated to methyl malonyl-GoA in a reaction catalyzed by propionyl-GoA carboxylase, which then undergoes... 

---