Carbon Fatty acid

Although vegetable oils and animals fats were commonly used in ancient times, most higher acids were not known until the beginning of the nineteenth century. Then the nature of the naturally occurring 18-carbon fatty acids was estabHshed, and hundreds of long-chain fatty acids have been isolated from natural sources and characterized. 

Mobilization of Fats from Dietary Intake and Adipo.se Ti.ssne /3-Oxidation of Fatty Acids /3-Oxidation of Odd-Carbon Fatty Acids /3-Oxidation of Unsatnrated Fatty Acids Other Aspects of Fatty Acid Oxidation... 

Oxidation of Odd-Carbon Fatty Acids Yields Propionyl-CoA... 

Fatty acids with odd numbers of carbon atoms are rare in mammals, but fairly common in plants and marine organisms. Humans and animals whose diets include these food sources metabolize odd-carbon fatty acids via the /3-oxida-tion pathway. The final product of /3-oxidation in this case is the 3-carbon pro-pionyl-CoA instead of acetyl-CoA. Three specialized enzymes then carry out the reactions that convert propionyl-CoA to succinyl-CoA, a TCA cycle intermediate. (Because propionyl-CoA is a degradation product of methionine, valine, and isoleucine, this sequence of reactions is also important in amino acid catabolism, as we shall see in Chapter 26.) The pathway involves an initial carboxylation at the a-carbon of propionyl-CoA to produce D-methylmalonyl-CoA (Figure 24.19). The reaction is catalyzed by a biotin-dependent enzyme, propionyl-CoA carboxylase. The mechanism involves ATP-driven carboxylation of biotin at Nj, followed by nucleophilic attack by the a-carbanion of propi-onyl-CoA in a stereo-specific manner. 

FIGURE 24.19 The conversion of propi-onyl-CoA (formed from /3-oxidation of odd-carbon fatty acids) to succinyl-CoA is carried out by a trio of enzymes as shown. Succinyl-CoA can enter the TCA cycle or be converted to acetyl-CoA. 

Succinyl-CoA derived from propionyl-CoA can enter the TCA cycle. Oxidation of succinate to oxaloacetate provides a substrate for glucose synthesis. Thus, although the acetate units produced in /3-oxidation cannot be utilized in glu-coneogenesis by animals, the occasional propionate produced from oxidation of odd-carbon fatty acids can be used for sugar synthesis. Alternatively, succinate introduced to the TCA cycle from odd-carbon fatty acid oxidation may be oxidized to COg. However, all of the 4-carbon intermediates in the TCA cycle are regenerated in the cycle and thus should be viewed as catalytic species. Net consumption of succinyl-CoA thus does not occur directly in the TCA cycle. Rather, the succinyl-CoA generated from /3-oxidation of odd-carbon fatty acids must be converted to pyruvate and then to acetyl-CoA (which is completely oxidized in the TCA cycle). To follow this latter route, succinyl-CoA entering the TCA cycle must be first converted to malate in the usual way, and then transported from the mitochondrial matrix to the cytosol, where it is oxida-... 

Mammals can add additional double bonds to unsaturated fatty acids in their diets. Their ability to make arachidonic acid from linoleic acid is one example (Figure 25.15). This fatty acid is the precursor for prostaglandins and other biologically active derivatives such as leukotrienes. Synthesis involves formation of a linoleoyl ester of CoA from dietary linoleic acid, followed by introduction of a double bond at the 6-position. The triply unsaturated product is then elongated (by malonyl-CoA with a decarboxylation step) to yield a 20-carbon fatty acid with double bonds at the 8-, 11-, and 14-positions. A second desaturation reaction at the 5-position followed by an acyl-CoA synthetase reaction (Chapter 24) liberates the product, a 20-carbon fatty acid with double bonds at the 5-, 8-, IT, and ITpositions. 

Eicosanoids, so named because they are all derived from 20-carbon fatty acids, are ubiquitous breakdown products of phospholipids. In response to appropriate stimuli, cells activate the breakdown of selected phospholipids (Figure 25.27). Phospholipase Ag (Chapter 8) selectively cleaves fatty acids from the C-2 position of phospholipids. Often these are unsaturated fatty acids, among which is arachidonic acid. Arachidonic acid may also be released from phospholipids by the combined actions of phospholipase C (which yields diacyl-glycerols) and diacylglycerol lipase (which releases fatty acids). 

The 20 carbon fatty acid, 5,8,11,14 - eicosatetranoic acid, an essential fatty acid that serves as a precursor for protaglandins. 

Myristoylation is the post-translational addition of the 14-carbon fatty acid myristate to the N-terminal glycine of proteins via an amide link. Myristoylation of proteins helps to anchor them to membranes. 

GHB is an endogenous, water-soluble, four-carbon fatty acid that is found in peripheral organs, including the heart, liver, kidney, and cardiac and skeletal... 

The melting points of even-numbered-carbon fatty acids increase with chain length and decrease according to unsaturation. A triacylglycerol containing three sam-rated fatty acids of 12 carbons or more is solid at body temperature, whereas if the fatty acid residues are 18 2, it is liquid to below 0 °C. In practice, natural acylglyc-erols contain a mixture of fatty acids tailored to suit their functional roles. The membrane lipids, which must be fluid at all environmental temperatures, are... 

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. 

Macrolide aggregation pheromones produced by male cucujid beetles are derived from fatty acids. Feeding experiments with labeled oleic, linoleic, and palmitic acids indicate incorporation into the macrolide pheromone component [ 117 ]. The biosynthesis of another group of beetle pheromones, the lactones, involves fatty acid biosynthetic pathways. Japonilure and buibuilactone biosynthesized by the female scarab, Anomalajaponica, involves A9 desaturation of 16 and 18 carbon fatty acids to produce Z9-16 CoA and Z9-18 CoA,hydroxylation at carbon 8 followed by two rounds of limited chain shortening and cyclization to the lactone [118]. The hydroxylation step appears to be stereospecific [118]. 

Propionyl CoA carboxylase Odd-carbon fatty acids, Val, Alopecia (hair loss), bowel inflammation. 

Cya n ocobalamin (Bir) Homocysteine methyltransferase Methylmalonyi CoA mutase Methionine, SAM Odd-carbon fatty acids, Val, Met, He, Thr MCC pernicious anemia. Also in aging, especially with poor nutrition, bacterial overgrowth of terminal ileum, resection of the terminal ileum secondary to Crohn disease, chronic pancreatitis, and, rarely, vegans, or infection with D. latum Megaloblastic (macrocytic) anemia Progressive peripheral neuropathy. ... 

In humans, it is not possible to convert acetyl CoA to glucose. Inasmuch as most fatty acids are metabolized solely to acetyl CoA, they are not a major source of glucose either. One minor exception are odd-number carbon fatty acids (e.g., C17), which yield a small amount of propi-onyl CoA that is gluconeogenic. 

Valine, methionine, isoleucine, and threonine are all metabolized through the propionic acid pathway (also used for odd-carbon fatty acids). Defidency of either enzyme results in neonatal ketoacidosis from failure to metabolize ketoacids produced from these four amino adds. The defidendes may be distinguished based on whether meth)dmalonic adduria is present. A diet low in protein or a semisynthetic diet with low amounts of valine, methionine, isoleudne, and threonine is used to treat both deficiencies. 

The key substrate for synthesis of the eicosanoids is the omega-6,20-carbon fatty acid arachidonic acid ... 

Conversion of 2-carbon units to a 16-carbon fatty acid... 

Seed oil triglycerides consist of three fatty acids esterified to glycerin. Although most plants produce at least some Cie fatty acids, the majority of the triglycerides are comprised of Cig fatty acids. The balance of the fatty acids is quite specific to the plant from which the oil is derived, but the most prominent fatty acids among all plant species consist of a series of 18-carbon fatty acids containing zero, one, two, or three sites of unsaturation. These fatty acids are stearic, oleic, linoleic, and linolenic acids, respectively. These are the main fatty acids found in most seed oils and are illustrated in Fig. 5. 

Figure 1.9. Overview of the biosynthesis of ecosanoids. The 20 carbon fatty acid arachidonic acid is released from cell membrane phospholipids by the actions of phospholipase A2. Free arachidonic acid forms the precursor of prostaglandins and thromboxanes via the multi-enz5une cyclooxygenase pathway, while leukotrienes are formed via the lipoxygenase pathway...

Prostaglandin (PC). Components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. 

Melting Points of Lipids The melting points of a series of 18-carbon fatty acids are stearic acid, 69.6 °C oleic acid, 13.4 °C linoleic acid, - 5 °C and linolenic acid, - 11 °C. (a) What structural aspect of these 18-carbon fatty acids... 

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. 

Compare the following the diameters of (a) a carbon atom in an organic molecule (b) a bacterial cell, e.g. of E. coli (c) a human red blood cell (d) a ribosome (e) the length of a peptide unit in an extended polypeptide chain (f) the length of the carbon atom chain in an 18-carbon fatty acid. 

The simplest or lowest member of the fatly acid series is formic acid, HCOOH. followed by acetic acid, CHiCOOH. propionic acid with three carbons, butyric acid with four carbons, valeric acid with five carbons, and upward to palmitic acid with sixteen carbons, stearic acid with eighteen carbons and melissic acid with thirty carbons. Fatty acids are considered to be the oxidation product of saturated primary alcohols. These acids are stable, being very difficult [with the exception of formic acid) to convert to simpler compounds they easily undergo double decomposition because of the carboxyl group they combine with alcohols to form esters and water they yield halogen-subslitulion products they convert to acid chlorides when reacted with phosphorus pcntachloridc and Iheir acidic qualities decrease as their formula weight increases. 

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