Palmitate biosynthesis

See also Palmitate Biosynthesis from Acetyl-CoA, Fatty Acid Biosynthesis Strategy, Synthesis of Long Chain Fatty Acids, Figure 18.29, Figure 18.30, Fatty Acids... 

L-Ascorbic acid biosynthesis in plants and animals as well as the chemical synthesis starts from D-glucose. The vitamin and its main derivatives, sodium ascorbate, calcium ascorbate, and ascorbyl palmitate, are officially recognized by regulatory agencies and included in compendia such as the United S fates Pharmacopeia/National Formula (USP/NF) and the Food Chemicals Codex (FCC). 

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. 

Seven cycles are implicated in palmitic acid biosynthesis and, accordingly, seven malonyl residues and one acetyl are required. Acetyl is the end moiety in fatty acid biosynthesis. The palmitic acid thus synthetized is either transferred onto the outer CoA to produce acyl-CoA, or, more commonly, is hydrolyzed by the specific palmitate deacylase to yield a free fatty acid. 

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. 

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]. 

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. 

Scheme 23 Example of an acyl carrier protein (ACP in red) in a type I FAS. The palmitic acid is depicted as a representative fatty acid. During its biosynthesis, the ACP (red) interacts iteratively with each domain (DH, dehydrogenase ER, enoyl reductase KR, ketoreductase KS, ketosynthase TE, thioesterase) until the palmitic acid has reached its proper length.

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. 

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. 

The biosynthesis of fatty acids such as palmitate thus requires acetyl-CoA and the input of chemical energy7 in two forms the group transfer potential of ATP and the reducing power of NADPH. The ATP is required to attach C02 to acetyl-CoA to make malonyl-CoA the NADPH is required to reduce the double bonds. We return to the sources of acetyl-CoA and NADPH soon, but first let s consider the structure of the remarkable enzyme complex that catalyzes the synthesis of fatty acids. 

Net Equation of Fatty Acid Synthesis Write the net equation for the biosynthesis of palmitate in rat liver, starting from mitochondrial acetyl-CoA and cytosolic NADPH, ATP, and C02. 

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. 

Write the sequence of steps and the net reaction for the biosynthesis of phosphatidylcholine by the salvage pathway from oleate, palmitate, dihydroxyacetone phosphate, and choline. Starting from these precursors, what is the cost (in number of ATPs) of the synthesis of phosphatidylcholine by the salvage pathway ... 

Since the amounts of fatty acids available for acylation during the biosynthesis of milk TGs affect their placement, feeding protected oils can be expected to alter the structure of the TGs. The data of Christie and Clapperton (1982) show that total and therefore all positional 18 2s are higher than in normal milk. Palmitic acid (16 0) decreases reciprocally. 

In plants most biosynthesis occurs in the chloro-plasts or in the protoplastids of seeds.72-75 There are two different synthase systems in chloroplasts, one that forms primarily the 16 0 palmitoyl-ACP and the other the 18 0 stearoyl-ACP. Hydrolysis of the palmitoyl-ACP releases palmitate, one major product of chloroplasts. However, the stearoyl-ACP is desaturat-ed to oleoyl-ACP75a before hydrolysis to free oleate or conversion to oleoyl-CoA. In many species oleic acid is almost the sole fatty acid exported by the chloroplasts. However, it undergoes a variety of modification reactions in the plant cytosol. 

Isoprene is also a precursor of steroids and terpenes. This relationship becomes clear when we examine the biosynthesis of these compounds (see chapter 20). Vitamin A is either biosynthesized from /3-carotene (see fig. S2.4) or absorbed in the diet. Vitamin A is stored in the liver predominantly as an ester of palmitic acid. For many decades, it has been... 

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. 

What are the metabolic sources of NADPH used in fatty acid biosynthesis How many moles of NADPH are required for the synthesis of 1 mole of palmitic acid from acetyl-CoA ... 

Glucose-6-phosphate dehydrogenase, 6-phosphoglu-conate dehydrogenase, and the NADP+-malic enzyme are sources of the 14 moles of NADPH required for biosynthesis of palmitate. 

The typical secondary metabolites of soft corals are diterpenoids, although some species also produce sesquiterpenoids. The sesquiterpene portion of furoquinol (Structure 2.102) is labeled by [2-3H]mevalonolactone in Sinularia capillosa,m while Heteroxenia sp. converts acetate and meva-lonate into cubebol (Structure 2.103) and clavukerin A (Structure 2.104).188 In contrast, acetate is used for cetyl palmitate synthesis in Alcyonium molle, but not for de novo diterpene biosynthesis.188... 

The pathway The first committed step in fatty acid biosynthesis is the carboxylation of acetyl CoA to form malonyl CoA which is catalyzed by the biotin-containing enzyme acetyl CoA carboxylase. Acetyl CoA and malonyl CoA are then converted into their ACP derivatives. The elongation cycle in fatty acid synthesis involves four reactions condensation of acetyl-ACP and malonyl-ACP to form acetoacetyl-ACP releasing free ACP and C02, then reduction by NADPH to form D-3-hydroxybutyryl-ACP, followed by dehydration to crotonyl-ACP, and finally reduction by NADPH to form butyryl-ACP. Further rounds of elongation add more two-carbon units from malonyl-ACP on to the growing hydrocarbon chain, until the C16 palmitate is formed. Further elongation of fatty acids takes place on the cytosolic surface of the smooth endoplasmic reticulum (SER). 

Fatty acids usually have an even number of carbons because they are biosynthesized from acetate ion, which has two carbons. Those with 14, 16, 18, and 20 carbons are most common. Their biosynthesis is outlined in Figure 28.10. They may be saturated, like stearic acid and palmitic acid, or they may have one or more CC double bonds, like... 

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