Lipid primary

Bile acids The major metabolites of cholesterol, which are synthesized in the liver and stored in the gallbladder for use as emulsifiers in the digestion of lipids. Primary bile acids are those synthesized directly from cholesterol in the liver Secondary bile acids are metabolites of primary bile acids produced by the action of intestinal bacteria. 

The interest in vesicles as models for cell biomembranes has led to much work on the interactions within and between lipid layers. The primary contributions to vesicle stability and curvature include those familiar to us already, the electrostatic interactions between charged head groups (Chapter V) and the van der Waals interaction between layers (Chapter VI). An additional force due to thermal fluctuations in membranes produces a steric repulsion between membranes known as the Helfrich or undulation interaction. This force has been quantified by Sackmann and co-workers using reflection interference contrast microscopy to monitor vesicles weakly adhering to a solid substrate [78]. Membrane fluctuation forces may influence the interactions between proteins embedded in them [79]. Finally, in balance with these forces, bending elasticity helps determine shape transitions [80], interactions between inclusions [81], aggregation of membrane junctions [82], and unbinding of pinched membranes [83]. Specific interactions between membrane embedded receptors add an additional complication to biomembrane behavior. These have been stud-... 

Similar techniques have been used for simulating lipids in a membrane and other systems. The primary limitation of this method is developing interaction potentials accurately. 

Water solubility (polarity) is essential for excretion. Even though lipid-soluble compounds may also be excreted to primary urine, they are usually at least partially reabsorbed. The metabolites formed in the liver and extrahe-patic tissues remain free (i.e., not bound to proteins) and are, therefore, readily excreted. 

Accumulation of lipids in the liver (steatosis) is one possible mechanism for liver toxicity. Several compounds causing necrosis of hepatocytes also cause steatosis. There are, however, some doubts that steatosis would be the primary cause of liver injury. Several compounds cause steatosis (e.g., puro-mycin, cycloheximide) without causing liver injury. Most of the accumulated lipids are triglycerides. In steatosis, the balance between the synthesis and excretion of these lipids has been disturbed (see Table 5.13). 

Primary ( ) amines e.g. alkyl amines [1—3] lipid amines [4] a, co-diamines [5, 6] polyamines [6] alkanol amines [7] subst. anilines [8] aminoglycoside antibiotics [9, 10] biogenic amines [11] hydrazines... 

HDL and VLDL are assembled primarily in the endoplasmic reticulum of the liver (with smaller amounts produced in the intestine), whereas chylomicrons form in the intestine. LDL is not synthesized directly, but is made from VLDL. LDL appears to be the major circulatory complex for cholesterol and cholesterol esters. The primary task of chylomicrons is to transport triacylglycerols. Despite all this, it is extremely important to note that each of these lipoprotein classes contains some of each type of lipid. The relative amounts of HDL and LDL are important in the disposition of cholesterol in the body and in the development of arterial plaques (Figure 25.36). The structures of the various... 

The livers and intestines of animals are the primary sources of circulating lipids. Chylomicrons carry triacylglycerol and cholesterol esters from the intestines to other tissues, and VLDLs carry lipid from liver, as shown in Figure 25.38. At... 

Because skin exhibits many of the properties of a lipid membrane, dermal penetration can often be enhanced by increasing a molecule s lipophilicity. Preparation of an ester of an alcohol is often used for this purpose since this stratagem simultaneously time covers a hydrophilic group and provides a hydrophobic moiety the ready cleavage of this function by the ubiquitous esterase enzymes assures availability of the parent drug molecule. Thus acylation of the primary alcohol in flucinolone (65) with propionyl chloride affords procinonide (66) the same transform... 

FATP5 KO mice have been characterized in two studies focusing on the role of FATP5 in hepatic lipid and bile metabolism. LCFA uptake in primary hepato-cytes isolated from FATP5 KO mice was reduced by 50% and hepatic lipid content in the KO mice was significantly reduced despite an increased fatty acid de novo biosynthesis. Detailed analysis of the hepatic lipidome of FATP5 KO mice revealed significant... 

Phloretin inhibits FATP-mediated traversing of fatty acids across lipid bilayers. Phloretin is the aglycon of phlorizin and has been used to terminate the uptake of LCFAs and VLCFAs in timed in vitro uptake assays with cultured cells or in ex vivo uptake assays with isolated primary cells. 

Sometimes a paradoxical elevation of blood lipid levels occurs Should this happen, the primary health care provider is notified because the primary health care provider may prescribe a different antihyperiipidemic drug. 

Because the maximum effects of these drugs are usually seen within 4 weeks, periodic lipid profiles are performed to determine the therapeutic effect of the drag regimen. The primary health care provider may increase... 

The diversity in primary, secondary, tertiary, and quaternary stmctures of proteins means that few generalisations can be made concerning their chemical properties. Some fulfil stmctural roles, such as the collagens (found in bone) and keratin (found in claws and beaks), and are insoluble in all solvents. Others, such as albumins or globulins of plasma, are very soluble in water. Still others, which form part of membranes of cells, are partly hydrophilic ( water-loving , hence water-soluble) and partly lipophilic ( lipid-loving , hence fat-soluble). 

Fatty acids are synthesized by an extramitochondrial system, which is responsible for the complete synthesis of palmitate from acetyl-CoA in the cytosol. In the rat, the pathway is well represented in adipose tissue and liver, whereas in humans adipose tissue may not be an important site, and liver has only low activity. In birds, lipogenesis is confined to the liver, where it is particularly important in providing lipids for egg formation. In most mammals, glucose is the primary substrate for lipogenesis, but in ruminants it is acetate, the main fuel molecule produced by the diet. Critical diseases of the pathway have not been reported in humans. However, inhibition of lipogenesis occurs in type 1 (insulin-de-pendent) diabetes mellitus, and variations in its activity may affect the nature and extent of obesity. 

The ion channel receptors are relatively simple in functional terms because the primary response to receptor activation is generated by the ion channel which is an integral part of the protein. Therefore, no accessory proteins are needed to observe the response to nicotinic AChR activation and the full functioning of the receptor can be observed by isolating and purifying the protein biochemically and reconstituting the protein in an artificial lipid membrane. In contrast, the G-protein-coupled receptors require both G-proteins and those elements such as phospholipase-C illustrated in Fig. 3.1, in order to observe the response to receptor activation (in this case a rise in intracellular calcium concentration resulting from the action of IP3 on intracellular calcium stores). 

Fig. 16.1 Progression of oxidation in a food system from formation of radicals through primary and secondary lipid oxidation products to protein damage.

Lipid hydroperoxides are either formed in an autocatalytic process initiated by hydroxyl radicals or they are formed photochemically. Lipid hydroperoxides, known as the primary lipid oxidation products, are tasteless and odourless, but may be cleaved into the so-called secondary lipid oxidation products by heat or by metal ion catalysis. This transformation of hydroperoxides to secondary lipid oxidation products can thus be seen during chill storage of pork (Nielsen et al, 1997). The secondary lipid oxidation products, like hexanal from linoleic acid, are volatile and provide precooked meats, dried milk products and used frying oil with characteristic off-flavours (Shahidi and Pegg, 1994). They may further react with proteins forming fluorescent protein derivatives derived from initially formed Schiff bases (Tappel, 1956). 

A number of methods are available for following the oxidative behaviour of food samples. The consumption of oxygen and the ESR detection of radicals, either directly or indirectly by spin trapping, can be used to follow the initial steps during oxidation (Andersen and Skibsted, 2002). The formation of primary oxidation products, such as hydroperoxides and conjugated dienes, and secondary oxidation products (carbohydrides, carbonyl compounds and acids) in the case of lipid oxidation, can be quantified by several standard chemical and physical analytical methods (Armstrong, 1998 Horwitz, 2000). 

Interaction of lipid oxidation products and amino compounds. Amino acids and primary amines may be involved in other reactions which could lead to the formation of compounds having the potential to undergo N-nitrosation. Malonaldehyde, produced as a result of oxidation of lipids, particularly polyunsaturated fatty acids, has been shown to react with amino acids to produce... 

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