Fatty acid phosphorylation

In general, the presence of fatty acid groups in the phosphoHpid molecule permits reactions such as saponification, hydrolysis, hydrogenation, halogenation, sulfonation, phosphorylation, elaidinization, and ozonization (6). 

Phosphorus. Eighty-five percent of the phosphoms, the second most abundant element in the human body, is located in bones and teeth (24,35). Whereas there is constant exchange of calcium and phosphoms between bones and blood, there is very Httle turnover in teeth (25). The Ca P ratio in bones is constant at about 2 1. Every tissue and cell contains phosphoms, generally as a salt or ester of mono-, di-, or tribasic phosphoric acid, as phosphoHpids, or as phosphorylated sugars (24). Phosphoms is involved in a large number and wide variety of metaboHc functions. Examples are carbohydrate metaboHsm (36,37), adenosine triphosphate (ATP) from fatty acid metaboHsm (38), and oxidative phosphorylation (36,39). Common food sources rich in phosphoms are Hsted in Table 5 (see also Phosphorus compounds). 

The processes of electron transport and oxidative phosphorylation are membrane-associated. Bacteria are the simplest life form, and bacterial cells typically consist of a single cellular compartment surrounded by a plasma membrane and a more rigid cell wall. In such a system, the conversion of energy from NADH and [FADHg] to the energy of ATP via electron transport and oxidative phosphorylation is carried out at (and across) the plasma membrane. In eukaryotic cells, electron transport and oxidative phosphorylation are localized in mitochondria, which are also the sites of TCA cycle activity and (as we shall see in Chapter 24) fatty acid oxidation. Mammalian cells contain from 800 to 2500 mitochondria other types of cells may have as few as one or two or as many as half a million mitochondria. Human erythrocytes, whose purpose is simply to transport oxygen to tissues, contain no mitochondria at all. The typical mitochondrion is about 0.5 0.3 microns in diameter and from 0.5 micron to several microns long its overall shape is sensitive to metabolic conditions in the cell. 

Regulatory Control of Fatty Acid Metabolism—An Interplay of Allosteric Modifiers and Phosphorylation-Dephosphorylation Cycles... 

The fatty acids released on triacylglycerol hydrolysis are transported to mitochondria and degraded to acetyl CoA, while the glycerol is carried to the liver for further metabolism. In the liver, glycerol is first phosphorylated by reaction with ATP. Oxidation by NAD+ then yields dihydroxyacetone phosphate (DHAP), which enters the carbohydrate metabolic pathway. We ll discuss this carbohydrate pathway in more detail in Section 29.5. 

The development of monoalkyl phosphate as a low skin irritating anionic surfactant is accented in a review with 30 references on monoalkyl phosphate salts, including surface-active properties, cutaneous effects, and applications to paste and liquid-type skin cleansers, and also phosphorylation reactions from the viewpoint of industrial production [26]. Amine salts of acrylate ester polymers, which are physiologically acceptable and useful as surfactants, are prepared by transesterification of alkyl acrylate polymers with 4-morpholinethanol or the alkanolamines and fatty alcohols or alkoxylated alkylphenols, and neutralizing with carboxylic or phosphoric acid. The polymer salt was used as an emulsifying agent for oils and waxes [70]. Preparation of pharmaceutical liposomes with surfactants derived from phosphoric acid is described in [279]. Lipid bilayer vesicles comprise an anionic or zwitterionic surfactant which when dispersed in H20 at a temperature above the phase transition temperature is in a micellar phase and a second lipid which is a single-chain fatty acid, fatty acid ester, or fatty alcohol which is in an emulsion phase, and cholesterol or a derivative. 

Senior, A.E. Shenatt, H.S.A. (1968). Biochemical effects of the hypoglycaemic compound pent-4-enoic acid and related non-hypoglycemic fatty acids. Oxidative phosphorylation and mitochondrial oxidation of pyruvate, 3-hydroxybutyrate and tricarboxylic acid-cycle intermediates. Biochem. J. 110,499-509. 

Mammalian proteins are the targets of a wide range of covalent modification processes. Modifications such as glycosylation, hydroxylation, and fatty acid acylation introduce new structural features into newly synthesized proteins that tend to persist for the lifetime of the protein. Among the covalent modifications that regulate protein function (eg, methylation, adenylylation), the most common by far is phosphorylation-dephos-phorylation. Protein kinases phosphorylate proteins by... 

Pathways are compartmentalized within the cell. Glycolysis, glycogenesis, glycogenolysis, the pentose phosphate pathway, and fipogenesis occur in the cytosol. The mitochondrion contains the enzymes of the citric acid cycle, P-oxidation of fatty acids, and of oxidative phosphorylation. The endoplasmic reticulum also contains the enzymes for many other processes, including protein synthesis, glycerofipid formation, and dmg metabolism. 

Acetyl-CoA carboxylase is an allosteric enzyme and is activated by citrate, which increases in concentration in the well-fed state and is an indicator of a plentiful supply of acetyl-CoA. Citrate converts the enzyme from an inactive dimer to an active polymeric form, having a molecular mass of several milhon. Inactivation is promoted by phosphorylation of the enzyme and by long-chain acyl-CoA molecules, an example of negative feedback inhibition by a product of a reaction. Thus, if acyl-CoA accumulates because it is not esterified quickly enough or because of increased lipolysis or an influx of free fatty acids into the tissue, it will automatically reduce the synthesis of new fatty acid. Acyl-CoA may also inhibit the mitochondrial tricarboxylate transporter, thus preventing activation of the enzyme by egress of citrate from the mitochondria into the cytosol. 

Several enzymes, known collectively as fatty acid oxidase, are found in the mitochondrial matrix or inner membrane adjacent to the respiratory chain. These catalyze the oxidation of acyl-CoA to acetyl-CoA, the system being coupled with the phosphorylation of ADP to ATP (Figure 22-3). 

A modified form of P-oxidation is found in peroxisomes and leads to the formation of acetyl-CoA and H2O2 (from the flavoprotein-linked dehydrogenase step), which is broken down by catalase. Thus, this dehydrogenation in peroxisomes is not linked directly to phosphorylation and the generation of ATP. The system facilitates the oxidation of very long chain fatty acids (eg, Cjq, C22). These enzymes are induced by... 

Of the two major phosphohpid classes present in membranes, phosphoglycerides are the more common and consist of a glycerol backbone to which are attached two fatty acids in ester linkage and a phosphorylated alcohol (Figure 41-2). The fatty acid constiments are usually even-numbered carbon molecules, most commonly containing 16 or 18 carbons. They are unbranched and can be saturated or unsamrated. The simplest phosphoglyceride is phosphatidic acid, which is... 

Figure 41-2. A phosphoglyceride showing the fatty acids (R, and Rj), glycerol, and phosphorylated alcohol components. In phosphatidicacid, Rjis hydrogen.

The Wassermann substance17 is prepared by extracting various animal organs, particularly beef heart, with alcohol, and its lipidal nature was early recognized. Pangborn174 described the preparation of a new phospholipid termed cardiolipin from beef heart and claimed that it was the essential constituent of the Wassermann substance. On hydrolysis it gave a fatty acid and a phosphorylated polysaccharide. In a later communication17 however, the carbohydrate constituent is stated... 

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