Saturated fatty acids, biosynthesis

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... 

Thus D. salina provides an experimental system in which prokaryotic galac-tolipid biosynthesis can be examined with a virtual absence of eukaryotic galactolipid formation. A further experimental asset is that radioactivity administered in the form of C-16 0 remains entirely within Cjg fatty acids, saturated and unsaturated, and that fed as C-18 l is recovered only in... 

In addition, in vivo C MR spectroscopy has been applied to the study of adipose tissue composition in disease. Children with cystic fibrosis were shown to have lower levels of polyunsaturated adipose tissue fatty acids than healthy children, possibly owing to a disorder in essential fatty acid metabolism that may be partly responsible for the development of the disease. Further studies with in vivo MRS in disease have shown a significant increase in saturated adipose tissue fatty acids following transplantation and subsequent weight gain in malnourished patients with liver cirrhosis. It was suggested that this increase in saturated fatty acids may be secondary to a general repletion of membrane polyunsaturated fatty acids or the use of essential fatty acids for biosynthesis of eicosanoids in the postoperative period. 

The next three steps—reduction of the /3-carbonyl group to form a /3-alcohol, followed by dehydration and reduction to saturate the chain (Figure 25.7) — look very similar to the fatty acid degradation pathway in reverse. However, there are two crucial differences between fatty acid biosynthesis and fatty acid oxidation (besides the fact that different enzymes are involved) First, the alcohol formed in the first step has the D configuration rather than the L form seen in catabolism, and, second, the reducing coenzyme is NADPH, although NAD and FAD are the oxidants in the catabolic pathway. 

The stimulus for the recent surge of activity in this previously dormant area of organic chemistry can be traced to the prostaglandin connection . That is to the discovery that saturated bicyclic peroxides are key intermediates in the biosynthesis of prostaglandins and other physiologically active substances by the enzymatic oxygenation of polyunsaturated fatty acids. 

Once an enzyme-catalysed reaction has occurred the product is released and its engagement with the next enzyme in the sequence is a somewhat random event. Only rarely is the product from one reaction passed directly onto the next enzyme in the sequence. In such cases, enzymes which catalyse consecutive reactions, are physically associated or aggregated with each other to form what is called a multi enzyme complex (MEC). An example of this arrangement is evident in the biosynthesis of saturated fatty acids (described in Section 6.30). Another example of an organized arrangement is one in which the individual enzyme proteins are bound to membrane, as for example with the ATP-generating mitochondrial electron transfer chain (ETC) mechanism. Intermediate substrates (or electrons in the case of the ETC) are passed directly from one immobilized protein to the next in sequence. 

The common fatty acids have a linear chain containing an even number of carbon atoms, which reflects that the fatty acid chain is built up two carbon atoms at a time during biosynthesis. The structures and common names for several common fatty acids are provided in table 18.1. Fatty acids such as palmitic and stearic acids contain only carbon-carbon single bonds and are termed saturated. Other fatty acids such as oleic acid contain a single carbon-carbon double bond and are termed monounsaturated. Note that the geometry around this bond is cis, not trans. Oleic acid is found in high concentration in olive oil, which is low in saturated fatty acids. In fact, about 83% of all fatty acids in olive oil is oleic acid. Another 7% is linoleic acid. The remainder, only 10%, is saturated fatty acids. Butter, in contrast, contains about 25% oleic acid and more than 35% saturated fatty acids. 

In the vertebrates, biosynthesis of fatty acids is catalyzed by fatty add synthase, a multifunctional enzyme. Located in the cytoplasm, the enzyme requires acetyl CoA as a starter molecule. In a cyclic reaction, the acetyl residue is elongated by one C2 unit at a time for seven cycles. NADPH+H is used as a reducing agent in the process. The end product of the reaction is the saturated Cie acid, palmitic acid. 

Menendez, R., R. Mas, A. M. Amor, I. Rodeiros, R. M. Gonzalez, and J. L. Alfonso. Inhibition of cholesterol biosynthesis in cultured fibroblasts by D-003, a mixture of very long chain saturated fatty acids. Pharmacol Res... 

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... 

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. 

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... 

Figure 17-12 The reactions of cytoplasmic biosynthesis of saturated fatty acids. Compare with pathway of (3 oxidation (Fig. 17-1).

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. 

Anaerobic pathway for biosynthesis of monounsaturated fatty acids in E. coli. Synthesis of monounsaturated fatty acids follows the pathway described previously for saturated fatty acids until the intermediate j8-hydroxydecanoyl-ACP is reached. At this point an apparent competition arises between the enzymes involved in saturated and unsaturated fatty acid synthesis. 

As the name anaerobic implies, the double bond of the fatty acid is inserted in the absence of oxygen. Biosynthesis of monounsaturated fatty acids follows the pathway described previously for saturated fatty acids until the intermediate /3-hydroxydecanoyl-ACP is reached (fig. 18.15). At this point, a new enzyme, /3-hydroxydecanoyl-ACP dehydrase, becomes involved. This dehydrase can form the a-j8 trans double bond, and saturated fatty acid synthesis can occur as previously discussed. In addition, this dehydrase is capable of isomerization of the double bond to a cis /3-y double bond as shown in figure 18.15. The /3-y unsaturated fatty acyl-ACP is subsequently elongated by the normal enzymes of fatty acid synthesis to yield pal-mitoleoyl-ACP (16 1A9). The conversion of this compound to the major unsaturated fatty acid of E. coli, cA-vacccnic acid (18 1A11), requires a condensing enzyme that we have not previously discussed, /3-ketoacyl-ACP synthase II, which shows a preference for palmitoleoyl-ACP as a substrate. The subsequent conversion to vaccenyl-ACP is cata-... 

Enzyme complexes occur in the endoplasmic reticulum of animal cells that desaturate at A5 if there is a double bond at the A8 position, or at A6 if there is a double bond at the A9 position. These enzymes are different from each other and from the A9-desaturase discussed in the previous section, but the A5 and A6 desaturases do appear to utilize the same cytochrome b5 reductase and cytochrome b5 mentioned previously. Also present in the endoplasmic reticulum are enzymes that elongate saturated and unsaturated fatty acids by two carbons. As in the biosynthesis of palmitic acid, the fatty acid elongation system uses malonyl-CoA as a donor of the two-carbon unit. A combination of the desaturation and elongation enzymes allows for the biosynthesis of arachidonic acid and docosahexaenoic acid in the mammalian liver. As an example, the pathway by which linoleic acid is converted to arachidonic acid is shown in figure 18.17. Interestingly, cats are unable to synthesize arachidonic acid from linoleic acid. This may be why cats are carnivores and depend on other animals to make arachidonic acid for them. Also note that the elongation system in the endoplasmic reticulum is important for the conversion of palmitoyl-CoA to stearoyl-CoA. 

Biosynthesis of dipalmitoylphosphatidylcholine. R2 is usually an unsaturated fatty acid. Thus this two-step reaction results in the replacement of an unsaturated by a saturated fatty acid at the C-2 position on the glycerol backbone. Dipalmitoylphosphatidylcholine is... 

Like the related fatty acid synthases (FASs), polyketide synthases (PKSs) are multifunctional enzymes that catalyze the decarboxylative (Claisen) condensation of simple carboxylic acids, activated as their coenzyme A (CoA) thioesters. While FASs typically use acetyl-CoA as the starter unit and malonyl-CoA as the extender unit, PKSs often employ acetyl- or propionyl-CoA to initiate biosynthesis, and malonyl-, methylmalonyl-, and occasionally ethylmalonyl-CoA or pro-pylmalonyl-CoA as a source of chain-extension units. After each condensation, FASs catalyze the full reduction of the P-ketothioester to a methylene by way of ketoreduction, dehydration, and enoyl reduction (Fig. 3). In contrast, PKSs shortcut the FAS pathway in one of two ways (Fig. 4). The aromatic PKSs (Fig. 4a) leave the P-keto groups substantially intact to produce aromatic products, while the modular PKSs (Fig. 4b) catalyze a variable extent of reduction to yield the so-called complex polyketides. In the latter case, reduction may not occur, or there may be formation of a P-hydroxy, double-bond, or fully saturated methylene additionally, the outcome may vary between different cycles of chain extension (Fig. 4b). This inherent variability in keto reduction, the greater variety of... 

Methyl-branched fatty acids are intermediates in branched alkane biosynthesis (Juarez et al., 1992). Thus, [l-14C]propionate labeled methyl-branched fatty acids of 16-20 carbons, but did not label straight chain-saturated and monounsaturated fatty acids (Chase et al., 1990). 

Mutations in desatl affect HC, resulting in a very large decrease in 7-HC in males, and in 7- and 7,11-HC in females, with a parallel increase in saturated HC synthesis (Labeur el al., 2002 Ueyama el al., 2005 Marcillac et al., 2005a,b). Lipid metabolism is impaired too, with both quantitatively and qualitatively altered fatty acid biosynthesis the overall quantity of fatty acids was shown to be reduced by half and that of vaccenic acid, the common precursor to 7-HC in both sexes, reduced by a factor of six in a desatl mutant (Ueyama et al., 2005). 

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