Phospholipids lipid metabolism

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... 

Lipoproteins. A lipoprotein is an endogenous macromolecule consisting of an inner apolar core of cholesteryl esters and triglycerides surrounded by a monolayer of phospholipid embedded with cholesterol and apoproteins. The functions of lipoproteins are to transport lipids and to mediate lipid metabolism. There are four main types of lipoproteins (classified based on their flotation rates in salt solutions) chylomicrons, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). These differ in size, molecular weight, and density and have different lipid, protein, and apoprotein compositions (Table 11). The apoproteins are important determinants in the metabolism of lipoproteins—they serve as ligands for lipoprotein receptors and as mediators in lipoproteins interconversion by enzymes. 

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). 

Lipid metabolism. The liver synthesizes fatty acids from acetate units. The fatty acids formed are then used to synthesize fats and phospholipids, which are released into the blood in the form of lipoproteins. The liver s special ability to convert fatty acids into ketone bodies and to release these again is also important (see p. 312). 

Lipid metabolism in the liver is closely linked to the carbohydrate and amino acid metabolism. When there is a good supply of nutrients in the resorptive (wellfed) state (see p. 308), the liver converts glucose via acetyl CoA into fatty acids. The liver can also take up fatty acids from chylomicrons, which are supplied by the intestine, or from fatty acid-albumin complexes (see p. 162). Fatty acids from both sources are converted into fats and phospholipids. Together with apoproteins, they are packed into very-low-density lipoproteins (VLDLs see p.278) and then released into the blood by exocytosis. The VLDLs supply extrahepatic tissue, particularly adipose tissue and muscle. 

Lipid metabolism. Oil, administered orally to female C57BL/6 mice weaned at 21 d of age at a dose of 15% w/w for 6 weeks, increased the total lipids, triglycerides, LDL and VLDL cholesterol, and thioharhituric acid-reactive substances (TEARS) and reduced glutathione concentrations, without changes in phospholipids or total cho-... 

Several studies have evaluated the effects of oral di(2-ethylhexyl) adipate on various aspects of hepatic lipid metabolism. Feeding di(2-ethylhexyl) adipate (2% of diet) to male Wistar rats for seven days resulted in increased hepatic fatty acid-binding protein as well as in increased microsomal stearoyl-CoA desaturation activity (Kawashima et al., 1983a,b). Feeding the compound at this dose for 14 days resulted in increased levels of hepatic phospholipids and a decline in phosphatidyl-choline phosphatidylethanolamine ratio (Yanagita et al., 1987). Feeding di(2-ethyl-hexyl) adipate (2% of diet) to male NZB mice for five days resulted in induction of fatty acid translocase, fatty acid transporter protein and fatty acid binding protein in the liver (Motojima et al., 1998). 

The accumulation of fat is a common cellular response to toxic compounds, which is normally reversible. Usually triglycerides accumulate, although sometimes phospholipids accumulate, as occurs after exposure to the drug chlorphentermine (see chap. 2). Steatosis is particularly common in the liver as this organ has a major role in lipid metabolism (Fig. 6.15). The lipid may appear in the cell as many small droplets or as one large droplet. Interference with lipid metabolism can occur at several points ... 

Pantothenic acid participates as part of coenzvme A in carbohydrate metabolism (2-carbon transfer-acetate, or pyruvate), lipid metabolism (biosynthesis and catabolism of fatty acids, sterols, +phospholipids), protein metabolism (acetylations of amines and amino acids), porphyrin metabolism, acetylcholine production, isoprene production. 

Jackowski, S., J. E. Cronan, and C. O. Rock, Lipid metabolism in procaryotes. In D. E. Vance, and J. E. Vance (eds.), Biochemistry of Lipids, Lipoproteins and Membranes. Amsterdam Elsevier Science Publishers, 1991. This chapter (2) provides an advanced treatment of genetics and metabolism of phospholipids in E. coli. 

Very little is known about lipid metabolism in parasites, although in several aspects, it is quite different from that of the mammalian host. Lipids, like phospholipids, triacylglycerols and cholesterol, are not synthesized de novo by parasitic flatworms, but are obtained directly from the host (cholesterol) or are synthesized from building blocks obtained from the host (fatty acids and in case of phospholipids, also the head groups). A schematic and partly hypothetical overview of the main pathways of lipid metabolism in parasitic flat-worms is shown in Fig. 20.3. Fatty acids are... 

Apolipoprotein C-II can also be isolated from VLDL or HDL (H20, L5, N3). It contains 78 residues (J3) and has been shown by Chou-Fasman analysis to bind phospholipids (M26, M40), with three predicted helical sequences (M26). ApoC-II has attracted a great deal of attention because it activates one of the most important enzymes in plasma lipid metabolism, lipoprotein lipase, responsible for the hydrolysis of triglyceride in chylomicrons and VLDL. Sparrow and Gotto have summarized a number of studies on structure-function relationships (S52). These, taken together, indicate that there are separate functional domains in apoC-II, in that lipoprotein lipase activation is mediated by residues 55-78 and phospholipid binding by... 

In the early 1950s, several hormones were shown to enhance the incorporation of 32Pj into the anionic membrane phospholipid, phosphatidylinositol (for review see Ref. 1). In 1975, Michell [2] noted that agonists which influence inositol lipid metabolism also provoke Ca2+ mobilisation in stimulated cells. It was first thought... 

The major dietary lipids for humans are animal and plant triacylglycerols, sterols, and membrane phospholipids. The process of lipid metabolism fashions and degrades the lipid stores and produces the structural and functional lipids characteristic of individual tissues. For example, the evolution of a highly organized nervous system has depended on the natural selection of specific enzymes to synthesize and degrade (turn over) the lipids of the brain and central nervous system. 

Lipoproteins are essential for the transport of lipids from the gut and liver to the tissues, and for lipid metabolism. Lipoproteins are spherical particles with a hydrophobic core, covered by a single layer of amphi-pathic molecules phospholipids, cholesterol and one or more apoproteins (of which ten have been isolated these are produced in the liver). The role of these protein coverings is twofold they solubilise hydrophobic lipids and contain cell-targeting signals. 

The main effect of riboflavin deficiency is on lipid metabolism. In experimental animals on a riboflavin-free diet, feeding a high-fat diet leads to more marked impairment of growth, and a higher requirement for riboflavin to restore growth. There are also changes in the patterns of long-chain polyunsaturated fatty acids in membrane phospholipids. 

Fatty acids are incorporated into complex lipids through de novo synthetic and remodeling pathways. As detailed below and shown in Fig. 2a, intracellular pools of acyl-CoA are involved in processes outside of lipid metabolism and, in many instances, function as important regulatory molecules. Figure 2b illustrates an overview of glycerol phospholipid synthesis and how fatty acids in the form of acyl-CoA enter these metabolic pathways. Readers are referred to the article entitled Lipid Synthesis in this series for specific details regarding these pathways. 

Machoy-Mokrzynska, A., Put, A., Ceglecka, M., Mysliwie, Z. Influence of essential phospholipids (EPL) on selected biochemical parameters of lipid metabolism in rats chronically exposed to ammonium fluoride vapours. Eluoride 1994 27 201 -204... 

Finally, to underscore further redundancy as a hallmark of 2-AG inactivation pathways, strong evidence also exists for the direct esterification of this compound into neutral glycerolipids and phospholipids (Di Marzo et al. 1999a). The relevance of these pathways, which were already known when 2-AG was considered a mere intermediate in glyc-erol(phospho)lipid metabolism, to the regulation of the cannabinergic signal still need to be assessed. 

After synthesis in the various compartments of endoplasmic reticulum of alveolar type II cells, surfactant components are assembled in the cytosol into lamellar bodies. In the process of formation of lamellar bodies, the transfer of phospholipids between membranes is facilitated by phospholipid transfer proteins, which are nonenzymatic proteins found in all eukaryotic cells and which play an important role in lipid metabolism. There are three well-characterized phospholipid transfer proteins ... 

---