Hydrogenation of phospholipids

The original studies of hydrogenation of phospholipids dispersed in aqueous systems were performed using Wilkinson s catalyst introduced in a solvent vector of tetrahydrofuran [1, 9, 10], It was shown that complete hydrogenation of the dispersed lipid could be achieved under relatively mild conditions of temperature, hy-... 

The hydrogenation of phospholipid-bound unsaturated fatty acids by a homogeneous, water-soluble, palladium catalyst, Biochim.Biophys.Acta 92 1 (1987) 167-174... 

In 1977, Kellogg and Fridovich [28] showed that superoxide produced by the XO-acetaldehyde system initiated the oxidation of liposomes and hemolysis of erythrocytes. Lipid peroxidation was inhibited by SOD and catalase but not the hydroxyl radical scavenger mannitol. Gutteridge et al. [29] showed that the superoxide-generating system (aldehyde-XO) oxidized lipid micelles and decomposed deoxyribose. Superoxide and iron ions are apparently involved in the NADPH-dependent lipid peroxidation in human placental mitochondria [30], Ohyashiki and Nunomura [31] have found that the ferric ion-dependent lipid peroxidation of phospholipid liposomes was enhanced under acidic conditions (from pH 7.4 to 5.5). This reaction was inhibited by SOD, catalase, and hydroxyl radical scavengers. Ohyashiki and Nunomura suggested that superoxide, hydrogen peroxide, and hydroxyl radicals participate in the initiation of liposome oxidation. It has also been shown [32] that SOD inhibited the chain oxidation of methyl linoleate (but not methyl oleate) in phosphate buffer. 

This technique allowed us to prepare small colloids with a high proportion of AmB (33% molar proportion compared with 5% in AmBisome). However, at present we have used expensive, synthetic phospholipids. It may be possible to replace DMPC and DMPG by natural or partially hydrogenated natural phospholipids such as those from egg yolk or soy. This sort of economic consideration must be taken into account for the future development of the formulation. 

Trans fatty acids are produced during the commercial hydrogenation of plant oils (Chapter 11). Some margarines contain these fatty acids, as do some commercially prepared snack foods (e.g. biscnits, cookies, cakes, crisps, chips). In addition, bacteria in the rnmen of rnminants prodnce trans fatty acids, which are therefore present in dairy prodnce and meat. Trans fatty acids can be incorporated into the phospholipids of the plasma membrane of endothelial and other cells, resulting in damage to the membranes. Furthermore, these abnormal fatty acids can interfere in the production of thromboxanes, prostacyclins or leucotrienes and hence interfere in control of blood clotting, immune cell activity and inflammation (Chapter 11). 

PAMPA membranes typically consist of phospholipids dissolved in an organic solvent. Both of them affect chemical selectivity. Phospholipids facilitate the permeability of moderately hydrophilic molecules by ionic or hydrogen-bonding interactions (phopholipids are hydrogen bond acceptors). This allows permeation of moderately lipophilic compounds. Recently, it was shown that anionic phospholip-id(s) increases the permeation of basic compounds by ion pair mechanism [54—56]. Many PAMPA variants (and other artificial membrane tools) add anionic phospho-lipid(s) to increase the in vivo predictability. 

Lipids play an important part in the development of aroma in cooked foods, such as meat, by providing a source of reactive intermediates which participate in the Maillard reaction. Phospholipids appear to be more important than triglycerides. The addition of phospholipid to aqueous amino acid + ribose mixtures leads to reductions in the concentrations of heterocyclic compounds formed in the Maillard reaction. This effect could be due to lipid oxidation products reacting with simple Maillard intermediates, such as hydrogen sulfide and ammonia, to give compounds not normally found in the Maillard reaction. The precise nature of the odoriferous products obtained from lipid - Maillard interactions is dictated by the lipid structure and may depend on the fatty acid composition and the nature of any polar group attached to the lipid. 

Artificial membranes are used to study the influence of drug structure and of membrane composition on drug-membrane interactions. Artificial membranes that simulate mammalian membranes can easily be prepared because of the readiness of phospholipids to form lipid bilayers spontaneously. They have a strong tendency to self-associate in water. The macroscopic structure of dispersions of phospholipids depends on the type of lipids and on the water content. The structure and properties of self-assembled phospholipids in excess water have been described [74], and the mechanism of vesicle (synonym for liposome) formation has been reviewed [75]. While the individual components of membranes, proteins and lipids, are made up of atoms and covalent bonds, their association with each other to produce membrane structures is governed largely by hydrophobic effects. The hydrophobic effect is derived from the structure of water and the interaction of other components with the water structure. Because of their enormous hydrogen-bonding capacity, water molecules adopt a structure in both the liquid and solid state. 

A comparison of thermodynamic data on denaturation of globular proteins with that of fibrillar proteins and melting of phospholipid membranes led to a conclusion that the van der Waals contribution to the stabilization of protein structure is of the same order as that of hydrogen bonds (Priva-lov, 1982 see also Crigbaum and Komoria, 1979a,b). 

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