Fatty acids, activation formation

Further examples of acylphosphates are found in fatty acyl-AMPs (see Section 15.4.1) and aminacyl-AMPs (see Section 13.5), activated intermediates in the metabolism of fatty acids and formation of peptides respectively. Each of these is attacked on the C=0 by an appropriate S or O nucleophile, displacing the phosphate derivative AMP. 

Burstein and Hunter (1995) observed that THC stimulated the biosynthesis of anandamide in neuroblastoma cells employing either ethanolamine or arachidonic acid as the label. Anandamide bios5mthesis has also been shown to occur in primary cultures of rat brain neurons labelled with [H]-ethanolamine when stimulated with ionomycin, a Ca ionophore (Di Marzo et al. 1994). These authors proposed an alternate model for the biosynthesis of anandamide in which N-arachidonoyl phosphatidyl ethanolamine is cleaved by a phospholipase D activity to yield phosphatidic acid and ararchidonoylethanolamide. This model is based upon extensive studies undertaken by Schmid and collaborators (1990), who have shown that fatty acid ethanolamide formation results from the N-acylation of phosphatidyl ethanolamine by a transacylase to form N-acyl phosphatidylethanolamine. Possibly resulting from postmortem changes, this compound is subsequently hydrolyzed to the fatty acid ethanolamide and the corresponding phosphatide by a phosphodiesterase, phospholipase D. 

One ATP is used in the formation of glycerol 3-phosphate and three ATPs are used to convert three fatty acids to acyl CoAs. The three PPi formed during fatty acid activation are converted to Pj, hence, the total of seven Pj in the equation above. 

A. Activation of Fatty Acids The Formation of aThioester with Coenzyme A... 

A pathway for fatty acid activation, involving a reaction with nonphosphorylated high-energy intermediates rather than the formation of acetyl-CoA derivatives has also been postulated. The supporting evidence includes the observations that (1) blocking the electron transport chain with cyanide or uncoupling oxidative phosphorylation with dinitrophenol interferes with the fatty acid oxidation (2) oligomycin, which blocks the biosynthesis of ATP but does not affect the formation... 

Fatty Acid Oxidation Spiral. The individual reactions of fatty acid oxidation require the activation of the fatty acid by formation of a thioester with CoA. Subsequent oxidation, dehydration, oxidation, and cleavage all occur only with the acyl CoA compounds (II). The product... 

Krebs Cycle and Fatty Acid Oxidation. A possible role of Krebs cycle intermediates in supporting fatty acid oxidation is now apparent. Complete oxidation to CO2 requires oxalacetate to introduce acetyl CoA into the citric acid cycle. But even the formation of acetoacetate requires the continued generation of ATP to support the activation of fatty acids. The transfer of electrons from fatty acid to oxygen is coupled with phosphate esterification, so that fatty acid oxidation has the theoretical capacity to be self-supporting. In the crude systems that contain all of the essential factors for fatty acid oxidation, fatty acid activation must compete with other reactions for the available ATP, and maximum rates of oxidation occur only when additional ATP is generated through operation of the Krebs cycle. 

Acetate and fatty acid activation enzymes - —acetylation of ATP with formation of acetyl AMP and PPi, replacement of AMP by CoA. 

Lipase, phospholipase and lipoxygenase are the enzymes primarily responsible for poor-quality rice bran oil. They are activated during the bran removal process (Vetrimani et al., 1992 Takano, 1993), and can cause the rate of free fatty acid (FFA) formation to be as high as 5-7% per day (Nasirullah et al., 1989). Thus, inactivation of lipases is important for producing high-quality rice bran oil. The quality of rice bran oil is inversely related to the level of FFA, and this must be kept low if the oil is to be edible and acceptable in frying applications. However, the removal of FFA is not a simple process and is accompanied by the loss of important antioxidants (Krishna et ai, 2001). This loss must be kept to a minimum if rice bran oil is to be used as a functional food component. 

This is because a strong feedback (inhibitory) effect of acetyl-CoA (or a related metabolite) on system A (fatty acid activation, transport, and -oxidation) will strongly oppose the increase in the rate of formation of acetyl-CoA via an increase in the extracellular concentration of fatty acids. This is similar to the control of glycolysis in muscle, where the powerful feedback effect of the adenine nucleotides makes it difflcult to increase glycolysis by increasing the supply of glucose. 

Fabric Softeners, Surfactants and Bleach Activators. Mono- and bisamidoamines and their imidazoline counterparts are formed by the condensation reaction of one or two moles of a monobasic fatty acid (typically stearic or oleic) or their methyl esters with one mole of a polyamine. Imidazoline formation requires that the ethyleneamine have at least one segment in which a secondary amine group Hes adjacent to a primary amine group. These amidoamines and imidazolines form the basis for a wide range of fabric softeners, surfactants, and emulsifiers. Commonly used amines are DETA, TETA, and DMAPA, although most of the polyethylene and polypropane polyamines can be used. 

Formation of Malonyl-CoA Activates Acetate Units for Fatty Acid Synthesis... 

FIGURE 25.2 (a) The acetyl-CoA carboxylase reaction produces malonyl-CoA for fatty acid synthesis, (b) A mechanism for the acetyl-CoA carboxylase reaction. Bicarbonate is activated for carboxylation reactions by formation of N-carboxybiotin. ATP drives the reaction forward, with transient formation of a carbonylphosphate intermediate (Step 1). In a typical biotin-dependent reaction, nncleophilic attack by the acetyl-CoA carbanion on the carboxyl carbon of N-carboxybiotin—a transcarboxylation—yields the carboxylated product (Step 2). 

The first domain of one subunit of the fatty acid synthase interacts with the second and third domains of the other subunit that is, the subunits are arranged in a head-to-tail fashion (Figure 25.9). The first step in the fatty acid synthase reaction is the formation of an acetyl-O-enzyme intermediate between the acetyl group of an acetyl-CoA and an active-site serine of the acetyl trails-... 

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. 

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