Lipid soluble substances

Traditionally, dried or powdered plant material is used and extracts can be obtained by mixing the material with food-grade solvents like dichloromethane or acetone followed by washing, concentration, and solvent removal. The result is an oily product that may contain variable amounts of pheophytins and other chlorophyll degradation compounds usually accompanied by lipid-soluble substances like carotenoids (mainly lutein), carotenes, fats, waxes, and phospholipids, depending on the raw material and extraction techniques employed. This product is usually marketed as pheophytin after standardization with vegetable oils. 

Quinones, lipid-soluble substances involved in electron transport, can also be used as biomarkers. Lipski et al. (155) u.sed quinone analyses, physiological tests, and fatty acid profiles to differentiate Gram-negative non-fermentative bacteria isolated from biofilters. Quinone type was found to be an efficient method to group isolates prior to the analysis of results from the physiological tests. The detection of quinones appears to be restricted to the discrimination of isolated colonies and has limited potential to the analysis of mixed populations. 

The movement of substances between the blood and the extracellular fluid surrounding the cells in most tissues of the body occurs very readily. This exchange takes place at the level of the capillaries, the smallest blood vessels in the cardiovascular system whose walls are formed by a single layer of endothelial cells. Lipid-soluble substances are able to move across this layer of endothelial cells at any point because they can move directly through the plasma membrane by passing between the phospholipid molecules of the bilayer. The movement of water-soluble substances is limited to the multiple pores found between the cells however, it also takes place rapidly and efficiently. 

There is no solid evidence that relates human aging and reduction of carotenoid absorption. In some studies, old people have shown a lower (3-carotene absorption than that of young people (Madani and others 1989), whereas the opposite has also been reported by other studies (Sugarman and others 1991). The absorption of lipid-soluble substances, including carotenoids, is affected by any disease related to the digestion and absorption of fats (West and Castenmiller 1998). Inadequate production of lipase and bile as well as an inadequate neutralization of the chyme in the duodenum affect carotenoid bioavailability (Guyton and Hall 2001). 

Simple diffusion is another mechanism by which substances cross membranes without the active participation of components in the membranes. Generally, lipid-soluble substances employ this method to enter cells. Both simple diffusion and filtration are dominant factors in most drug absorption, distribution, and elimination. 

Generally, to produce a biological response, a drug molecule must first cross at least one biological membrane. The biological membrane acts as a lipid barrier to most drugs and permits the absorption of lipid-soluble substances by passive diffusion while lipid-insoluble substances can diffuse if at all across the barrier only with considerable difficulty. The interrelationship of the dissociation constant, lipid solubility, and pH at the absorption site and absorption characteristics of various drugs are the basis of the pH-partition theory. 

Nitroglycerin is a lipid-soluble substance that is rapidly absorbed across the sublingual or buccal mucosa. Its onset of action occurs within 2 to 5 minutes, with maximal effects observed at 3 to 10 minutes. Little residual activity remains 20 to 30 minutes after sublingual administration. The plasma half-life of nitroglycerin, given... 

All neutral lipid-soluble substances have depressant (anesthetic) properties. 

Due to the rich blood and lymph supply to rectum the unionised and lipid soluble substances are readily absorbed from the rectum. The advantages of this route are that gastric irritation is avoided and easy administration by the patient himself. 

Lymph may also be of importance as a vehicle for facilitating absorption and transport of lipid-soluble substances but also of particles by specialized cells (M cells) in the gut-associated lymphoid tissue (GALT). 

Excretion into breast milk can be a very important route for certain types of foreign compounds, especially lipid-soluble substances, because of the high lipid content in milk. Clearly, newborn animals will be specifically at risk from toxic compounds excreted into milk. For example, nursing mothers exposed to DDT secrete it into their milk, and the infant may receive a greater dose, on a body-weight basis, than the mother. Also, because the pH of milk (6.5) is lower than the plasma, basic compounds may be concentrated in the fluid. 

One advantage of liposome is theirsingularability to take up material of all shapes and sizes regardles of their individual chemical peculiarities. The most relevant to this discussion is for lipid-soluble compounds, which are incorporated into the lipid bilayer of the liposome. Thus, the maximum amount taken up into liposomes is directly proportional to the quantity of membrane components, but is independent of the size of the liposomes used, except in a few cases where the structure o the encapsulated compound may restrict the Lnal size of the liposome. Theoretically, any type of liposome is suitable for the incorporation of lipid-soluble substances, but practical considerations make some choices more preferable over others. MLVs are the best choice for sustained release whereas SUVs are particularly suitable for rapid intermembrane transfer. 

Lipid-soluble substances traverse the membrane by dissolving in the lipoid phase, and the lipid-insoluble substances penetrate only when they are small enough to pass through the pores. The absorption of large lipid-insoluble substances such as sugars and amino acids is accomplished by specialized transport processes. 

The membrane separating fetal blood from maternal blood in the intervillous space, the placental barrier, resembles other membranes, in that lipid-soluble substances diffuse readily but water-... 

All classes of steroid hormones bind to specific cytoplasmic receptors in their respective target tissues, and are then translocated to the nucleus. For example, testosterone, a lipid-soluble substance, enters the cell and is enzymatically reduced to dihydrotestosterone by 5-a reductase. Dihydrotestosterone then becomes bound to a specific androgen receptor site located in the cytoplasm. This complex becomes activated and is then translocated to the nucleus, where it binds to the chromatin acceptor site consisting of DNA and nonhistone chromosomal proteins. This interaction results in the transcription of a specific messenger RNA that is then relocated to the cytoplasm and translated on the cytoplasmic ribosomes, resulting in the synthesis of a new protein that sponsors the androgenic functions (Figure 61.6). 

In general, the more lipid soluble a barbiturate derivative is, the greater is its plasma and tissuebinding capacity, the extent of its metabolism, and its storage in adipose tissues. In addition, very lipid-soluble substances have a faster onset of action and a shorter duration of action. 

The higher the molecular mass, the slower a substance is absorbed from the gastrointestinal tract. Assuming sufficient aqueous and lipid solubility, substances with molecular mass less than 300 daltons are typically well absorbed. Those with molecular mass ranging from 300 to 500 daltons are not as readily absorbed, and substances with molecular mass in the thousands are poorly absorbed, if at all (D Souza, 1990). 

Anthocyanins are generally more stable at an acidic pH. Therefore, anthocyanins are commonly extracted under cold conditions using either acidic methanol or ethanol to avoid degradation1 5169 (Table 3.4). In comparison, acetone allows more reproducible extraction and avoids problems with pectins. However, it is limited by the coextraction of proanthocyanins.39 In general, ethanol is preferable as an extraction solvent, although it can require an additional step for the removal of lipid-soluble substances. SPE using Ci8, polyamide, HLB (hydrophilic lipophilic balanced stationary phases), or Amberlite has been employed for the purification of anthocyanidins prior to HPLC analysis.39-51 66 69... 

Bilirubin is a lipid-soluble substance and for it to give a direct van den Bergh reaction it must be converted into a water-soluble state. This can be achieved in alkaline solution or by the use of solvents, such as ethanol, which are soluble in both water and chloroform (Cl). Conjugation with glucuronic acid also causes the solubilization of bilirubin and in view of the well-known versatility of the liver s detoxifying systems, the possibility that bilirubin may be conjugated with other substances has been considered. 

The permeability of the skin to a toxic substance is a function of both the substance and the skin. The permeability of the skin varies with both the location and the species that penetrates it. In order to penetrate the skin significantly, a substance must be a liquid or gas or significantly soluble in water or organic solvents. In general, nonpolar, lipid-soluble substances traverse skin more readily than do ionic species. Substances that penetrate skin easily include lipid-soluble endogenous substances (hormones, vitamins D and K) and a number of xenobiotic compounds. Common examples of these are phenol, nicotine, and strychnine. Some military poisons, such as the nerve gas sarin (see Section 18.8), permeate the skin very readily, which greatly adds to then-hazards. In addition to the rate of transport through the skin, an additional factor that influences toxicity via the percutaneous route is the blood flow at the site of exposure. 

This is the movement of substances across membranes by mechanisms which apparently follow the simple laws of diffusion, i.e. the rate of movement of a given substance is proportional to the concentration difference across the membrane. In the intestine, this appears to be the uptake mechanism of relatively few materials, among which are water-soluble vitamins, some nucleic acid derivatives and many lipid-soluble substances. 

Passive diffusion readily allows the transport of such lipid-soluble substances as oxygen and carbon dioxide, nicotine and heroin across the BBB, whereas none of the water-soluble nutrients and messenger molecules used by the brain can gain access via this route. Their access to the CNS is achieved by specialist transport systems, which selectively carry substances across the barrier. 

Figure 18.44. Uncoupler of Oxidative Phosphorylation. 2,4-Dinitrophenol, a lipid-soluble substance, can cany protons across the inner mitochondrial membrane. The dissociable proton is shown in red.

So-called standard papers are commercially available filter papers,t which tend to give the most reproducible results. Other papers are made for special purposes. For example, less dense papers are made for higher flow rates, and thicker papers for preparative purposes. Some are washed in add to remove traces of metals, and others are free of lipid-soluble substances. The cellulose may be modified chemically (esterification, hydroxylation) for specific purposes or impregnated with silicone oil (for reversed-phase chromatography). 

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