Carbon palmitate

In principle, fatty acids could be synthesised by the progressive addition of 2-carbon acetyl units to an extending acyl chain and reduction of the carbonyl groups to methylene groups that is, by reversal of the P-oxidation process, until the 16-carbon, palmitic acid is produced. However, for reasons already considered in this text, synthetic reac-... 

Continued condensation of malonyl-CoA with acetyl-CoA units is catalysed by fatty acid synthase, eventually leading to the 16-carbon palmitic acid (Figme 5.3) this is then released and may undergo separate elongation and/or unsaturation reactions, to yield other fatty acid molecules. The active form of fatty acid synthase is a dimer of identical subunits. 

Figure 4 Examples of short-chain and long-chain free fatty acids are shown (a) 4-carbon butyric acid and (b) 16-carbon palmitic acid.

The net effect of these eight steps is to take two acetyl groups and combine them into a single four-carbon butyryl group. Further condensation of butyryl synthase with another malonyl ACP yields a six-carbon unit, and still further repetitions of the pathway add two more carbon atoms to the chain each time until the 16-carbon palmitic acid is reached. Further chain elongation of palmitic acid occurs by reactions similar to those just described, but acetyl CoA itself rather than malonyl ACP is the two-carbon donor. 

A number of plants and phytochemicals have attracted attention for their ability to reduce many of the risk factors associated with cardiovascular disease. Research into these diseases has shown the relationship between lesions, fatty streaking and plaque formation in blood vessels and the development of strokes and myocardial infarctions. These effects are linked to levels of plasma lipids which comprise triglycerides, cholesterol and other fat substances. It is known that the biosynthesis of lipids involves the condensation of several molecules of acetylcoenzyme A and malonylcoenzyme A in a gradual process of elongation of the fatty acid chain involving the sequential addition of two carbon units giving rise to fatty acids such as lauric acid (12 carbons) and eventually to palmitic acid (16 carbons). Palmitic acid is the precursor... 

The problem of fat oxidation then resolves itself into that of the fate of the fatty acids derived from the fat. These, the straight chain acids stearic (18-carbon), palmitic (16-carbon), and oleic (18-carbon, one double bond), are oxidized, according to experimental results obtained byKnoop at the turn of the century, by a process which splits off the carbon atoms two at a time thus stearic is converted first to palmitic, then to a 14-carbon acid, then a 12-carbon acid, then a 10-carbon, and so on, until the molecule is whittled right down to the 4-carbon acetoaoetic acid, which is split in its turn into two 2-carbon acetic acid fragments. The removal of carbon atoms two at a time like this is called / -oxidation, as it occurs by the oxidation of the carbon atoms two places away from (in chemical parlance, in the /5-position to) the acidic group at the end of the fatty acid chain. 

Elongation of the acyl group to make fatty acids longer than 16 carbons (palmitate) occurs apart from palmitate synthesis. Whereas palmitate synthesis occurs in the cytosol, elongation occurs in both the mitochondria and endoplasmic reticulum (ER). The ER is the dominant system. Elongation in the ER differs from cytosolic synthesis in employing coenzyme A (instead of acyl carrier protein) and separate enzymes (instead of a complex). The condensation reaction occurs between malonyl-CoA and an acyl-CoA to form a / -ketoacyl-CoA (see here and here). Two enzymes catalyze this step in the endoplasmic reticulum, one of which is specific for unsaturated fatty acyl-CoAs. 

Carbon palmitic acid requires seven /3-oxidation cycles, which produce seven FADH2 and seven NADH. The total number of acetyl-CoA is eight. During electron transport, each FADH2 produces two ATP, and each NADH produces three ATP. Each acetyl-CoA can produce 12 ATP by way of the citric acid cycle. Two ATP are utilized in the activation of palmitic acid. 

This observation that the length of the hydrocarbon chain could be varied from 16 to 26 carbon atoms without affecting the limiting area could only mean that at this point the molecules were oriented vertically. From the molecular weight and density of palmitic acid, one computes a molecular volume of 495 A a molecule occupying only 21 A on the surface could then be about 4.5 A on the side but must be about 23 A long. In this way one begins to obtain information about the shape and orientation as well as the size of molecules. 

Qindamycin, 7(5)-7-chloro-7-deoxyliQcomycin [18323-44-9] (1, R = H, R = Q), also known as Cleocin, first resulted from the reaction of lincomycin and thionyl chloride (54) improved synthetic methods involve the reaction of lincomycin and triphenylphosphine dichloride or triphenylphosphine in carbon tetrachloride (55). Clindamycin is significantly more active than lincomycin against gram-positive bacteria in vitro, and is absorbed rapidly following oral adnainistration. Clindamycin 2-palmitate [36688-78-5], (6, R = R = OC(CH2) 4CH2), 2-palmitate ester of clindamycin, is... 

In essence, this series of four reactions has yielded a fatty acid (as a CoA ester) that has been shortened by two carbons, and one molecule of acetyl-CoA. The shortened fatty acyl-CoA can now go through another /3-oxidation cycle, as shown in Figure 24.10. Repetition of this cycle with a fatty acid with an even number of carbons eventually yields two molecules of acetyl-CoA in the final step. As noted in the first reaction in Table 24.2, complete /3-oxidation of palmitic acid yields eight molecules of acetyl-CoA as well as seven molecules of FADHg and seven molecules of NADFI. The acetyl-CoA can be further metabolized in the TCA cycle (as we have already seen). Alternatively, acetyl-CoA can also be used as a substrate in amino acid biosynthesis (Chapter 26). As noted in Chapter 23, however, acetyl-CoA cannot be used as a substrate for gluco-neogenesis. 

The elongation reactions are repeated until the growing chain reaches 16 carbons in length (palmitic acid). 

As seen already, palmitate is the primary product of the fatty acid synthase. Cells synthesize many other fatty acids. Shorter chains are easily made if the chain is released before reaching 16 carbons in length. Longer chains are made through special elongation reactions, which occur both in the mitochondria and at the surface of the endoplasmic reticulum. The ER reactions are actually quite similar to those we have just discussed addition of two-carbon units... 

Use the relationships shown in Figure 25.1 to determine which carbons of glucose will be incorporated into palmitic acid. Consider the cases of both citrate that is immediately exported to the cytosol following its synthesis and citrate that enters the TCA cycle. 

Petrol it. An old (1876) Dynamite contg NG 60, K or Na nitrate 16, carbon 16, sawdust 6, cetyl palmitate 1, and Na carbonate 1% (Ref 2) The same name was applied to a Ger chlorate expl introduced during WW1. It consisted of K chlorate, nitrocompds, kerosene, and neutral salts, and was considered a dangerous mixt (Ref 1)... 

The periodate-permanganate method used was based on a method described previously [105], but three changes from the original published procedure were found to be necessary. A sample size of 50 mg was taken for all oxidations. The same quantities of oxidant, potassium carbonate, and sodium bisulfite (26 ml, 45 mg, 1.06 g, respectively) were used for all samples. An inert marker (5 mg) of methyl palmite or stearate was added to all samples prior to oxidation to serve as a rough check on the completeness of oxidation and the recovery of fragments. 

A soap-based powder can be produced in combination with ester sulfonates. Thirty-five percent of a sodium soap mixture (5% lauric acid, 5% myristic acid, 52% palmitic acid, 21% stearic acid, 12% oleic acid, and 5% linoleic acid) is mixed with 15% sodium a-sulfo palm oil fatty acid methyl ester, 3% lauric acid ethoxylate, 5% sodium silicate, 17% sodium carbonate, 20% Na2S04- 10H2O, and 5% water [79]. 

The acetyl-CoA used as a primer forms carbon atoms 15 and 16 of palmitate. The addition of all the subsequent C2 units is via malonyl-CoA. Propionyl-CoA acts as primer for the synthesis of long-chain fatty... 

Fatty acids are often described by numbers such as 16 0, 18 1 or 18 3. The first number (16 or 18) is used to describe the number of carbon atoms in the chain whilst the second (0,1,3) gives the number of C=C double bonds in the molecule. Palmitic acid can therefore be shortened to 16 0 whilst oleic acid is 18 1... 

A suitable degree of esterification of dextran with butyric or palmitic acid is achieved by CDI in formamide or DMSO. In the absence of carboxylic acids dextran can be converted by CDI into a crosslinked product with intrachain as well as interchain carbonate links. Such carbonate links permit drugs containing hydroxyl groups to be coupled to the dextran.[174]... 

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]. 

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