Phospholipid plasma concentration

After administration of milligram Ginkgoselect Phytosome formulation (24% ginkgo-flavone glycosides and 6% terpenoids in phospholipid complex, 1 2). Abbreviations. N, number of subjects i.v., intravenous C ax, maximum plasma concentration tmux, time at ti/2(p), elimination half-life CL/F, clearance with regard to bioavailability F/F, volume of distribution with regard to bioavailability. 

The complex representation of Fig. 1 can be simplified to Fig. 2, which identifies three compartments that have to be assessed experimentally to apply the FA model. These compartments are (1) plasma unesterified FA, (2) the precursor brain FA-CoA pool, and (3) the stable brain phospholipid compartment (Rapoport et al., 1997 Robinson et al., 1992). Fluxes between them—J, J2, J pa—defined in the legend to Fig. 2. The simplified Fig. 2 can be used because (1) the half-life of the FA tracer in plasma is less than 1 min, (2) FA uptake into brain from bloodis independent of cerebral blood flow over a wide range of unlabeled FA plasma concentrations (Chang et al., 1997a Yamazaki et al., 1994), (3) labeled FA in plasma rapidly equilibrates (1 min or less) with label in FA-CoA, the precursor pool for FA incorporation into brain phospholipids, and (4) the FA tracer in brain is rapidly incorporated into brain phospholipids (80-90% within 1 min) (Rapoport et al., 1997 Robinson et al., 1992). 

The major lipids found in the bloodstream are cholesterol, cholesterol esters, triglycerides, and phospholipids. An excess plasma concentration of one or more of these compounds is known as hyperlipidemia. Because all lipids require the presence of soluble lipoproteins to be transported in the blood, hyperlipidemia ultimately results in an increased concentration of these transport molecules, a condition known as hyperlipoproteinemia. Hyperlipoproteinemia has been strongly associated with atherosclerotic lesions and coronary heart disease (CHD) (1,2). Before discussing lipoproteins, their role in cardiovascular disease, and agents to decrease their concentrations, it is essential to examine the biochemistry of cholesterol, triglycerides, and phospholipids. 

Class Buoyant density Plasma concentration (mg/ml) Protein (%of total) Lipid (% of total) Phospholipid (% of total) Ch-l-ChE (% of total) Triglyceride (% of total) Apoproteins present... 

Occurrence in Human Tissues. In an early report, Iversen et al. (19) determined that rumenic acid was present in human plasma phospholipids, with concentrations... 

Salt et al. (1960) noted in one family a decreased plasma concentration of jS-lipoproteins, cholesterol and phospholipids in assumed heterozygotes (parents and paternal grandfather). These observations have not been confirmed in other families. The possibility to recognize heterozygotes, therefore, remains questionable. 

Plasma lipid transfer proteins, which include the cholesteryl-ester-transfer-protein (CETP previously known as lipid transfer protein I, LTP-I) and the phospholipid-transfer-protein (PLTP previously known as lipid transfer protein II, LTP-II) mediate the transfer of lipids (cholesteryl esters, triglycerides and phospholipids) between lipoproteins present in human plasma. These proteins significantly affect plasma lipoprotein concentration and composition. 

PLTP is responsible for the majority of phospholipid transfer activity in human plasma. Specifically, it transfers surface phospholipids from VLDL to HDL upon lipolysis of triglycerides present in VLDL. The exact mechanism by which PLTP exerts its activity is yet unknown. The best indications for an important role in lipid metabolism have been gained from knockout experiments in mice, which show severe reduction of plasma levels of HDL-C and apoA-I. This is most likely the result of increased catabolism of HDL particles that are small in size as a result of phospholipid depletion. In addition to the maintenance of normal plasma HDL-C and apoA-I concentration, PLTP is also involved in a process called HDL conversion. Shortly summarized, this cascade of processes leads to fusion of HDL... 

The passage of a small and/or highly lipophilic molecule through the membrane phospholipid bilayer according to the gradient of its concentrations across the plasma membrane. It is slower than facilitated diffusion, which, however, also follows the gradient of solute concentrations across the membrane. 

A molecular variation of plasma membrane has been reported by Puccia et al. Reduction of total lipids (XL) content and significant variations of triglyceride (TG) and phospholipids (PL) fractions were observed as a consequence of exposure of C. intestinalis ovaries to TBTCl solutions. In particular, an evident TG decrease and a PL increase were observed, which probably provoked an increment in membrane fluidity, because of the high concentration of long chain fatty acids and, as a consequence, PL. This could be a cell-adaptive standing mechanism toward the pollutants, as observed in Saccharomyces cerevisiae. Also the increase in the content of the polyunsaturated fatty acids (PUPA), important in the synthesis of compounds such as prostaglandin which are present in the ovary in a stress situation, was probably a consequence of a defense mechanism to the stress provoked by the presence of TBTCl. 

HDL concentrations vary reciprocally with plasma triacylglycerol concentrations and directly with the activity of lipoprotein lipase. This may be due to surplus surface constituents, eg, phospholipid and apo A-I being released during hydrolysis of chylomicrons and VLDL and contributing toward the formation of preP-HDL and discoidal HDL. HDLj concentrations are inversely related to the incidence of coronary atherosclerosis, possibly because they reflect the efficiency of reverse cholesterol transport. HDL, (HDLj) is found in... 

Figure 25-5. Metabolism of high-density lipoprotein (HDL) in reverse cholesteroi transport. (LCAT, lecithinxholesterol acyltransferase C, cholesterol CE, cholesteryl ester PL, phospholipid A-l, apolipoprotein A-l SR-Bl, scavenger receptor B1 ABC-1, ATP binding cassette transporter 1.) Prep-HDL, HDLj, HDL3—see Table 25-1. Surplus surface constituents from the action of lipoprotein lipase on chylomicrons and VLDL are another source of preP-HDL. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of plasma HDLj in women.

The lag-phase measurement at 234 nm of the development of conjugated dienes on copper-stimulated LDL oxidation is used to define the oxidation resistance of different LDL samples (Esterbauer et al., 1992). During the lag phase, the antioxidants in LDL (vitamin E, carotenoids, ubiquinol-10) are consumed in a distinct sequence with a-tocopherol as the first followed by 7-tocopherol, thereafter the carotenoids cryptoxanthin, lycopene and finally /3-carotene. a-Tocopherol is the most prominent antioxidant of LDL (6.4 1.8 mol/mol LDL), whereas the concentration of the others 7-tocopherol, /3-carotene, lycopene, cryptoxanthin, zea-xanthin, lutein and phytofluene is only 1/10 to 1/300 of a-tocopherol. Since the tocopherols reside in the outer layer of the LDL molecule, protecting the monolayer of phospholipids and the carotenoids are in the inner core protecting the cholesterylesters, and the progression of oxidation is likely to occur from the aqueous interface inwards, it seems reasonable to assign to a-tocopherol the rank of the front-line antioxidant. In vivo, the LDL will also interact with the plasma water-soluble antioxidants in the circulation, not in the artery wall, as mentioned above. 

Most commonly, the lipid metabolism pathology is manifest as hyperlipemia (elevated concentration of lipids in blood) and tissue lipidoses (excessive lipid de-position in tissues). Normally, the lipid contents in the blood plasma are total lipids, 4-8 g/litre triglycerides, 0.5-2.1 mmol/litre total phospholipids, 2.0-3.5 mmol/litre total cholesterol, 4.0-8.0 mmol/litre (esterified cholesterol accounts for 2/3 of total cholesterol). 

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