Unsaturated fatty acids Biosynthesis

We focus first on the pathway of fatty acid synthesis, then turn our attention to regulation of the pathway and to the biosynthesis of longer-chain fatty acids, unsaturated fatty acids, and their eicosanoid derivatives. 

Fatty Acid Oxidation Yields Large Amounts of ATP Additional Enzymes Are Required for Oxidation of Unsaturated Fatty Acids in Mitochondria Ketone Bodies Formed in the Liver Are Used for Energy in Other Tissues Summary of Fatty Acid Degradation Biosynthesis of Saturated Fatty Acids... 

Figure 19.14 Biosynthesis of arachidonoyl-CoA from linoleoyl-CoA fatty acid unsaturation and elongation.

Nitrosohydrazones from culture filtrates of Strepto-myces sp. SK 1894, e.g., T. B CnHijNjO, Mr 205.26, yellow powder, mp. 144-147 °C T. A C,H,9N)0, Mr 209.29, yellow powder, mp. 116-118°C. T. inhibit various acyl-CoA synthetases, e.g., arachidonoyl-CoA synthetase and the synthetases of longer-chain fatty acids the biosynthesis of acetyl-CoA remains unaffected. Common structural feature of the T. is the -N-hydroxy-l-triazene unit, bound to an unsaturated aliphatic chain. 

Gas chromatography has been applied successfully to the separation and analysis of labeled compounds (chiefly those labeled with and in food samples. Studies have been made of the biosynthesis of unsaturated fatty acids, the effect of insulin on the biosynthesis of individual fatty acids, the biosynthesis of cholesterol, etc. Numerous studies deal with the incorporation of labeled compounds through foods into living organisms. 

Prostaglandins arise from unsaturated C20 carboxylic acids such as arachidonic acid (see Table 26 1) Mammals cannot biosynthesize arachidonic acid directly They obtain Imoleic acid (Table 26 1) from vegetable oils m their diet and extend the car bon chain of Imoleic acid from 18 to 20 carbons while introducing two more double bonds Lmoleic acid is said to be an essential fatty acid, forming part of the dietary requirement of mammals Animals fed on diets that are deficient m Imoleic acid grow poorly and suffer a number of other disorders some of which are reversed on feed mg them vegetable oils rich m Imoleic acid and other polyunsaturated fatty acids One function of these substances is to provide the raw materials for prostaglandin biosynthesis... 

Biosynthesis of Unsaturated Fatty Acids. In the mammalian tissues, the forma-tion of monoene fatty acids is only possible. Oleic acid is derived from stearic acid, and palmitooleic acid, from palmitic acid. This synthesis is carried out in the endoplasmic reticulum of the liver cells via the monooxigenase oxidation chain. Any other unsaturated fatty acids are not produced in the human organism and must be supplied in vegetable food (plants are capable of generating polyene fatty acids). Polyene fatty acids are essential food factors for mammals. 

Fatty acids are degraded by two-carbon units in a reverse manner analogous to their biosynthesis. The acyl-CoAs are first dehydrogenated to a,(3-unsaturated acyl-CoA, and then hydrated to (3-hydroxyacyl-CoA, followed by oxidation to (3-ketoacyl-CoA. The C-C bond between C-2 and C-3 of the latter compound is broken by a free CoA molecule via thiolysis to form an acyl-CoA that is two carbons shorter and acetyl-CoA. Unlike fatty acid biosynthesis, each step of the (3 oxidation of fatty acids is... 

FIGURE 3-7 Pathways for the interconversion of brain fatty acids. Palmitic acid (16 0) is the main end product of brain fatty acid synthesis. It may then be elongated, desaturated, and/or P-oxidized to form different long chain fatty acids. The monoenes (18 1 A7, 18 1 A9, 24 1 A15) are the main unsaturated fatty acids formed de novo by A9 desaturation and chain elongation. As shown, the very long chain fatty acids are a-oxidized to form a-hydroxy and odd numbered fatty acids. The polyunsaturated fatty acids are formed mainly from exogenous dietary fatty acids, such as linoleic (18 2, n-6) and a-linoleic (18 2, n-3) acids by chain elongation and desaturation at A5 and A6, as shown. A A4 desaturase has also been proposed, but its existence has been questioned. Instead, it has been shown that unsaturation at the A4 position is effected by retroconversion i.e. A6 unsaturation in the endoplasmic reticulum, followed by one cycle of P-oxidation (-C2) in peroxisomes [11], This is illustrated in the biosynthesis of DHA (22 6, n-3) above. In severe essential fatty acid deficiency, the abnormal polyenes, such as 20 3, n-9 are also synthesized de novo to substitute for the normal polyunsaturated acids. 

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. 

The biosynthesis of fatty acids produced during alcoholic fermentation is initiated in the yeast cell by the formation of acetylcoenzyme A, which reacts with malonylcoenzyme A to form mainly saturated straight-chained fatty acids with an even number of four to 18 carbon atoms the appearance of relatively low levels of fatty acids with odd numbers of carbon atoms as well as unsaturated fatty acids depends on the fermentation conditions [6]. The volatile fatty acids contribute to the flavour of fermented beverages like wine or beer and their concentration usually lies between 100 and 250 mg 0.1 L p.e. In distilled spirits the concentration of free fatty acids is significantly lower owing to the esterification... 

Studies on the biosynthesis of lactones have shown that epoxidation of unsaturated fatty acids like, e.g., linoleic and linolenic acid may represent a common pathway to oxygenated derivatives of fatty acids. Epoxy fatty acid hydrolases were identified as key enzymes that exhibit high regioselectivity and enantiose-lectivity [25, 26]. 

Butyric acid is one of the simplest fatty acids. Fatty acids, which are the building units of fats and oils, are natural compounds of carbon chains with a carboxyl group (-COOH) at one end. Most natural fatty acids have an unbranched carbon chain and contain an even number of carbon atoms because during biosynthesis they are built in two carbon units from acetyl coenzyme A (CoA). Butyric acid is an unsaturated fatty acid, which means all carbon-carbon bonds are single bonds. Common names for fatty acids stem from their natural sources. In addition to butyric acid, some other common saturated fatty acids include lauric acid, palmitic acid, and stearic acid. Lauric acid was first discovered in Lauraceae (Laurus nobilis) seeds, palmitic oil was prepared from palm oil, and stearic acid was discovered in animal fat and gets its name from the Greek word stear for tallow. 

Oxygen Requirement for I)esat,iirases The biosynthesis of palmitoleate (see Fig. 21-12), a common unsaturated fatty acid with a cis double bond in the A9 position, uses palmitate as a precursor. Can this be carried out under strictly anaerobic conditions Explain. 

Barbano and Sherbon (1981) found that feeding cows a protected poly unsaturated fat supplement had little influence on the fatty acid composition of the milk phospholipids. The biosynthesis of the pools of fatty acids from which milk phospholipids are synthesized is apparently independent of dietary input. 

Lecithins and related phospholipids usually contain a saturated fatty acid in the C-l position but an unsaturated acid, which may contain from one to four double bonds, at C-2. Arachidonic acid is often present here. Hydrolysis of the ester linkage at C-2 yields a l-acyl-3-phosphoglycerol, better known as a Iysophosphatidylcholine. The name comes from the powerful detergent action of these substances which leads to lysis of cells. Some snake venoms contain phospholipases that form Iysophosphatidylcholine. Lysophosphatidic acid (l-acyl-glycerol-3-phosphate) is both an intermediate in phospholipid biosynthesis (Chapter 21) and also a signaling molecule released into the bloodstream by activated platelets.15... 

A number of brilliant total syntheses of natural prostaglandins have been developed and these also have provided a number of interesting prostaglandin analogs (see Exercise 30-24). The biosynthesis of prostaglandins proceeds by oxygenation at Cl l of unsaturated fatty acids. This is followed by... 

Cells regulate the lipid compositions of their plasma membrane so that a reasonable membrane fluidity is main-tained. They do this by controlling fatty acid biosynthesis so as to vary the lengths of the fatty acid chains and the ratio of unsaturated to saturated fatty acids (see chapter 19). If cells are grown at low temperatures, their phospholipids contain more unsaturated fatty acids or fatty acids with shorter chains or both. These adjustments shift the Tm to lower temperatures, with the result that (to the extent that the melting transition is sharp enough to be measureable) the Tm re-... 

As mentioned in chapter 17, unsaturated fatty acids are abundant in all living organisms. Alternative mechanisms for the biosynthesis of unsaturated fatty acids have evolved. Two chemically distinct pathways exist for the introduction of a cis double bond into saturated fatty acids The anaero-bic pathway as typified in E. coli, and the aerobic pathway found in eukaryotes. 

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