Basic Lipids

The term lipid applies to a class of compounds that are soluble in organic solvents and nearly insoluble in water. Chemically, lipids are either compounds that yield fatty acids on hydrolysis or complex alcohols that combine with fatty acids to form esters. Some lipids are more complex, containing nonlipid groups, such as sialic, phosphoryl, amino. 

Cholesterol and cholesteryl esters Steroid hormones Bile acids Vitamin D 

Cholesterol is presented to the intestinal wall from three sources the diet, bile and intestinal secretions, and cells. Animal products—especially meat, egg yolk, seafood, and whole-fat dairy products— provide the bulk of dietary cholesterol. Although cholesterol intake varies considerably according to the dietary intake of animal products, the average American diet is estimated to contain approximately 300 to 450 mg of cholesterol per day. A similar amount of cholesterol is present in the gut from biliary secretion and the turnover of mucosal cells. Practically ail cholesterol in the intestine is present in the unesterified (free) form. Esterified cholesterol in the diet is rapidly hydrolyzed in the intestine to free cholesterol and free fatty acids by cholesterol esterases secreted from the pancreas and small intestine. 

In addition to animal cholesterol, approximately 200 to 300 mg of plant sterols are ingested daily. The most common plant sterol is P-sitosterol. Plant sterols differ from cholesterol only by small variations on the sterol side chain. Despite their close similarity to cholesterol, plant sterols are poorly absorbed. When plant sterols are administered in amounts of 5 to 15g/day, they significantly inhibit the absorption of cholesterol. Although the mechanism for reducing cholesterol absorption has not been determined, plant sterols have been used therapeutically in patients with elevated plasma cholesterol levels. 

After its absorption into the intestinal mucosal cell, cholesterol, together with triglycerides, phospholipids, and a number of specific apoproteins, is assembled into a large lipoprotein called the chylomicron (see later section on lipoprotein metabolism, exogenous pathway). One apoprotein component known as apolipoprotein (apo) B-48 is vital to the formation of chylomicrons, and in people with a rare deficiency of apo B-48 synthesis, chylomicron formation, and consequently cholesterol and fat absorption, is severely impaired. Chylomicrons enter the lymphatics, which empty into the thoracic duct and eventually enter the systemic venous circulation at the junction of the left subclavian vein and left internal jugular vein. 

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For a couple of centuries, scientists have been making an analogy between human metabolism and the burning of a candle. The analogy is really pretty good. A candle is basically lipid in nature and most of its carbon atoms are attached to hydrogen atoms. This is a low oxidation state, similar to that of methane. Much of our food is as well we call it fat. When a candle bums, it converts the candle wax into carbon... 

As detailed in chapter 17, biological membranes are basically lipid—think fat or oil—in nature with some attached proteins. As such, these thin sheets of phospholipids and proteins are nearly impermeable to charged particles such as sodium, potassium, or chloride ions. While the isolation of the cell interior from the exterior ionic environment is critical in many ways, it is also true that controlled permeability to ions may be critical. In fact, it is the near-impermeability of biological membranes to ions that permits control of ion transport across them by certain, specific proteins. 

Fatty liver refers to the abnormal accumulation of fat in hepatocytes. At the same time there is a decrease in plasma lipids and lipoproteins. Although many toxicants may cause lipid accumulation in the liver (Table 14.1), the mechanisms may be different. Basically lipid accumulation is related to disturbances in either the synthesis or the secretion of lipoproteins. Excess lipid can result from an oversupply of free fatty acids from adipose tissues or, more commonly, from impaired release of triglycerides from the liver into the plasma. Triglycerides are secreted from the liver as lipoproteins (very low density lipoprotein, VLDL). As might be expected, there are a number of points at which this process can be disrupted. Some of the more important ones are as follows (Figure 14.1) ... 

In insects, especially Diptera, several pioneer studies reviewed by Blomquist et al. (1987) established that long chain hydrocarbons, some of which play a pheromone role, were derived from very long chain fatty acids by reduction and decarboxylation. Thus, pheromone biosynthesis shares steps with those leading to basic lipid molecules and also with those of the well-known pheromones of Lepidoptera (Roelofs and Wolf, 1988). All often display several double bonds located in various positions while the volatile butterfly compounds bear functional groups (acetate, aldehyde or alcohol) and aliphatic chains with 12-16 carbons. Contact pheromones of flies have much longer chains (21C-39C) (Pennanec h et al., 1991). 

In order to explain the reason that marine oils are much more labile than common vegetable oUs, basic lipid chemistry, such as oxidation rate, induction period, and oxygen uptake were determined and reported by several researchers (70-72). The relative oxidation rates of fatty esters at 36.5°C were found to be highly... 

The solid lipids and the lipophilic drugs (see Figs. 1 and 2), either as powder or stock solutions are dissolved in 5-10 mL methanol/methylene chloride (1 1, v/v) in a round bottom flask (see Note 2). PEG-modified liposomes are obtained by addition of PEG(2000)-DPPE (28 mg/mL) to the basic lipid mixtures (see Note 3). 

In most membranes, the basic lipid bilayer fabric is enriched in various ways. The inner, fatty film of the bilayer often provides shelter for a number of hydrophobic molecules, for example cholesterol, which is an obligatory constituent of the outer membrane of all eukaryotic cells. Most importantly, all biological membranes contain a variety of specialized proteins of crucial importance. 

Another factor adds to an even more stunning complexity. This is due to the real structures of biomembranes. Built on the basic lipid bilayer, they insert a multitude of transmembrane proteins as well as diverse sugars with linear and branched structures into membrane that, in turn, can bind other proteins. Everybody who wishes to get a deeper insight into cell membranes should have a look at the Web site http //en.wikipedia.org7wild/Cell membrane. 

Johnston, P.V. "Basic Lipid Methodology" Special Publication 19, College of Agriculture, University of Illinois Urbana, 1971 p. 49. 

Johnston, P.V. (1971) Basic Lipid Methodology, University of Illinois Press, Urbana and Champaign, IL. 

Biological membranes or cell membranes have very complex structures because they must be able to accomplish specific functions. However, a characteristic of various cell membranes is that they contain a basic lipid bilayer structure. Each lipid molecule possess a hydrophobic and a hydrophilic part. A schematic drawing of such a lipid bilayer is given in figure II - 34. This structure exists in different types of cell membrane, the polar pan being situated at the water/membrane interface with the hydrophobic part being... 

I have previously noted the minimal impact of basic lipid research on chemotherapeutic approaches to atherosclerosis. In order to close on a hopeful and somewhat more positive note, I would like to call attention to three substances which interfere with specific events in lipid biosynthesis and do so by well understood mechanisms, 3-Decynoyl-N-acetyl-cysteamine, developed in our laboratory as a substrate analogue, has been shown to block the formation of unsaturated fatty acids in certain bacteria in a highly specific manner ( 2). The compound itself is not an inhibitor but a pseudosubstrate, converted by the target enzyme into the allenic isomer,... 

Chain models capture the basic elements of the amphiphilic behaviour by retaining details of the molecular architecture. Ben-Shaul et aJ [ ] and others [ ] explored the organization of tlie hydrophobic portion in lipid micelles and bilayers by retaining the confonuational statistics of the hydrocarbon tail withm the RIS (rotational isomeric state) model [4, 5] while representing the hydrophilic/liydrophobic mterface merely by an... 

We turn now to the biosynthesis of lipid structures. We begin with a discussion of the biosynthesis of fatty acids, stressing the basic pathways, additional means of elongation, mechanisms for the introduction of double bonds, and regulation of fatty acid synthesis. Sections then follow on the biosynthesis of glyc-erophospholipids, sphingolipids, eicosanoids, and cholesterol. The transport of lipids through the body in lipoprotein complexes is described, and the chapter closes with discussions of the biosynthesis of bile salts and steroid hormones. 

With the adequacy of lipid bilayer membranes as models for the basic structural motif and hence for the ion transport barrier of biological membranes, studies of channel and carrier ion transport mechanisms across such membranes become of central relevance to transport across cell membranes. The fundamental principles derived from these studies, however, have generality beyond the specific model systems. As noted above and as will be treated below, it is found that selective transport... 

As first shown by Hladky and Haydon 7,8), it is possible to observe the current due to a single transmembrane channel by using extensions of the planar lipid hilaver approach of Mueller and Rudin 9). The basic system is shown in Fig. 2 and is commonly referred to as the black lipid membrane (BLM) method. This is because, as the lipid in the hole between the two chambers thins, the areas that have become planar bilayers are seen as black. Additional terms are bilayer lipid membranes or planar lipid bilayer membranes. These lipid bilayer membranes, particularly those which are solvent free, have capacitances which are very close to those of biological membranes. 

At the N-terminal end of the f loop, near the membrane lipid interface, there is an autoinhibitory domain, rich in both basic and hydrophobic residues and consisting of a 20-aminoacid sequence (219-238). This aminoacid sequence, named exchange inhibitory peptide (XDP), is involved in NCX activity regulation. 

Liposomes are members of a family of vesicular structures which can vary widely in their physicochemical properties. Basically, a liposome is built of one or more lipid bilayers surrounding an aqueous core. The backbone of the bilayer consists of phospholipids the major phospholipid is usually phosphatidylcholine (PC), a neutral lipid. Size, number of bilayers, bilayer charge, and bilayer rigidity are critical parameters controlling the fate of liposomes in vitro and in vivo. Dependent on the preparation procedure unilamellar or multilamellar vesicles can be produced. The diameter of these vesicles can range from 25 nm up to 50 ym—a 2000-fold size difference. 

In this chapter we describe the basic principles involved in the controlled production and modification of two-dimensional protein crystals. These are synthesized in nature as the outermost cell surface layer (S-layer) of prokaryotic organisms and have been successfully applied as basic building blocks in a biomolecular construction kit. Most importantly, the constituent subunits of the S-layer lattices have the capability to recrystallize into iso-porous closed monolayers in suspension, at liquid-surface interfaces, on lipid films, on liposomes, and on solid supports (e.g., silicon wafers, metals, and polymers). The self-assembled monomolecular lattices have been utilized for the immobilization of functional biomolecules in an ordered fashion and for their controlled confinement in defined areas of nanometer dimension. Thus, S-layers fulfill key requirements for the development of new supramolecular materials and enable the design of a broad spectrum of nanoscale devices, as required in molecular nanotechnology, nanobiotechnology, and biomimetics [1-3]. 

FIG. 17 Schematic illustration of the setup for a tip-dip experiment. First glycerol dialkyl nonitol tetraether lipid (GDNT) monolayers are compressed to the desired surface pressure (measured by a Wilhehny plate system). Subsequently a small patch of the monolayer is clamped by a glass micropipette and the S-layer protein is recrystallized. The lower picture shows the S-layer/GDNT membrane on the tip of the glass micropipette in more detail. The basic circuit for measurement of the electric features of the membrane and the current mediated by a hypothetical ion carrier is shown in the upper part of the schematic drawing. 

The nature of the diet sets the basic pattern of metabohsm. There is a need to process the products of digestion of dietary carbohydrate, lipid, and protein. These are mainly glucose, fatty acids and glycerol, and amino acids, respectively. In ruminants (and to a lesser extent in other herbivores), dietary cellulose is fermented by symbiotic microorganisms to short-chain fatty acids (acetic, propionic, butyric), and metabohsm in these animals is adapted to use these fatty acids as major substrates. All the products of digestion are metabohzed to a common product, acetyl-CoA, which is then oxidized by the citric acid cycle (Figure 15-1). 

Figure 41-7. The fluid mosaic model of membrane structure. The membrane consists of a bimolecu-lar lipid layer with proteins inserted in it or bound to either surface. Integral membrane proteins are firmly embedded in the lipid layers. Some of these proteins completely span the bilayer and are called transmembrane proteins, while others are embedded in either the outer or inner leaflet of the lipid bilayer. Loosely bound to the outer or inner surface of the membrane are the peripheral proteins. Many of the proteins and lipids have externally exposed oligosaccharide chains. (Reproduced, with permission, from Junqueira LC, Carneiro J Basic Histology. Text Atlas, 10th ed. McGraw-Hill, 2003.)...

The basic structure of all membranes is the lipid bilayer. This bilayer is formed by two sheets of phospholipids in which the hydrophilic polar head groups... 

The actions of proteins isolated from sea anemones, or other coelenterates, involve mechanisms different from those described for saponins. Thus, hemolysins from sea anemone R macrodactylus are capable of forming ion channels directly in membranes (98). The basic protein from S. helianthus also forms channels in black-lipid membranes. These channels are permeable to cations and show rectification (99). This ability of S. helianthus toxin III to form channels depends upon the nature of the host lipid membrane (100). Cytolysin S. helianthus binds to sphingomyelin and this substance may well serve as the binding site in cell membranes (101-106). 

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