Saturated phospholipid

To study the possible effect of membrane biophysical properties on drug accumulation, the lipid composition of membranes has deliberately been altered by growing cells in the presence of anionic phospholipids, saturated or unsaturated fatty acids, or other components affecting membrane properties, e.g. cholesterol [102, 103]. The accumulation of drugs in MDR hamster cell lines (CHRC5) was increased when membrane properties were altered. For this purpose the cells were cultured in a medium supplemented with C17 0 fatty acid. The cells showed an extent of vinblastine accumulation similar to that found in the sensitive wild-type counterparts (AB1) (Figure 5.15) [103]. 

SpiUman T, Cotton DB, Lynn SC, Bretaudiere JP. Influence of phospholipid saturation on classical thin-layer chromatographic detection methods and its effect on amniotic fluid lecithin/sphingomyelin ratio determinations. Clin Chem 1983 29 250-5. 

Matsumoto, C., Hanson, N. Q., Tsai, M. Y., Glyim, R. J., Gaziano, J. M., Djousse, L. (2013). Plasma phospholipid saturated fatty acids and heart failure risk in the physicians health study. ClinNutr, 32(5), 819-823. 

There are other ways in which the lateral organization (and asymmetry) of lipids in biological membranes can be altered. Eor example, cholesterol can intercalate between the phospholipid fatty acid chains, its polar hydroxyl group associated with the polar head groups. In this manner, patches of cholesterol and phospholipids can form in an otherwise homogeneous sea of pure phospholipid. This lateral asymmetry can in turn affect the function of membrane proteins and enzymes. The lateral distribution of lipids in a membrane can also be affected by proteins in the membrane. Certain integral membrane proteins prefer associations with specific lipids. Proteins may select unsaturated lipid chains over saturated chains or may prefer a specific head group over others. 

Phospholipids are important constituents of cell membranes and are of two kinds. Glycerophospholipids, such as phosphatidylcholine and phos-phatidylethanolamine, are closely related to fats in that they have a glycerol backbone esterified to two fatty acids (one saturated and one unsaturaled) and to one phosphate ester. Sphingomyelins have the amino alcohol sphingo-sine for their backbone. 

Figure 41-3. Diagrammatic representation of a phospholipid or other membrane lipid. The polar head group is hydrophilic, and the hydrocarbon tails are hydrophobic or lipophilic. The fatty acids in the tails are saturated (S) or unsaturated (U) the former are usually attached to carbon 1 of glycerol and the latter to carbon 2. Note the kink in the tail of the unsaturated fatty acid (U), which is important in conferring increased membrane fluidity.

The lipid in muscle is composed primarily of triglycerides (depot fats) and of phospholipids (membrane components), and is a constituent which varies enormously not only in amount present, but also in properties such as degree of saturation (species dependent). The ash of lean meat is comprised of various minerals such as phosphorus, potassium, sodium, magnesium, calcium, iron and zinc Carbohydrate was not noted in the proximate composition because while some may be present, it is normally there in low concentration compared to the other constituents. Glycogen is the carbohydrate occurring in greatest concentration in muscle but is normally degraded soon after the animal is sacrificed. 

The evaluation of the apparent ionization constants (i) can indicate in partition experiments the extent to which a charged form of the drug partitions into the octanol or liposome bilayer domains, (ii) can indicate in solubility measurements, the presence of aggregates in saturated solutions and whether the aggregates are ionized or neutral and the extent to which salts of dmgs form, and (iii) can indicate in permeability measurements, whether the aqueous boundary layer adjacent to the membrane barrier, Umits the transport of drugs across artificial phospholipid membranes [parallel artificial membrane permeation assay (PAMPA)] or across monolayers of cultured cells [Caco-2, Madin-Darby canine kidney (MDCK), etc.]. 

Kakiuchi et al. [75] used the capacitance measurements to study the adsorption of dilauroylphosphatidylcholine at the ideally polarized water-nitrobenzene interface, as an alternative approach to the surface tension measurements for the same system [51]. In the potential range, where the aqueous phase had a negative potential with respect to the nitrobenzene phase, the interfacial capacity was found to decrease with the increasing phospholipid concentration in the organic solvent phase (Fig. 11). The saturated mono-layer in the liquid-expanded state was formed at the phospholipid concentration exceeding 20 /amol dm, with an area of 0.73 nm occupied by a single molecule. The adsorption was described by the Frumkin isotherm. 

SCDs are a family of microsomal Fe-based metalloenzymes. They act on long-chain saturated acyl CoAs and introduce a ds-double bond at the C-9 or C-10 position. For example, SCDs convert stearic acid into oleic acid, and palmitic acid into palmitoleic acid. Monounsaturated FAs constitute a major component of TGs, cholesteryl esters, and phospholipids. The reaction requires molecular 02 and NADH and generates H20 in the process [3,4]. 

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