G adipose tissue

Figure 7.3 The action of lipoprotein lipase in the hydrolysis of triacylglycerol in the blood and the fate of the fatty adds produced. Lipoprotein Lipase is attached to the luminal surface of the capillaries in the tissues that are responsible for removal of triacylglycerol from the bloodstream (e.g. adipose tissue, muscle, lactating mammary gland).

Figure 3.9 The structure of mammalian skin (A) epidermis, (B) dermis, (C) sebaceous gland, (D) capillary, (E) nerve fibers, (F) sweat gland, (G) adipose tissue, (H) hair.

Some of the lactic acid formed in muscle and most of the lactate formed in less aerobic tissues (e.g., adipose tissue)1363 enters the bloodstream, which normally contains 1-2 mM lactate,136 and is carried to the liver where it is reoxidized to pyruvate. Part of the pyruvate is then oxidized via the citric acid cycle while a larger part is reconverted to glucose (Section J,5). 

Reconstructive exposure assessment uses biological monitoring data, in conjunction with pharmacokinetic data and models, to estimate the levels of absorbed dose (e.g., systemic levels in plasma or whole blood), and in some cases, external exposure to a chemical that resulted in the measured levels in biological tissues and/or fluids. Biological monitoring consists of the measurement of the concentration of a chemical and/or its biotransformation products in biological tissues or fluids (e.g., adipose tissue, blood, urine) or the measurement of the amount of chemical bound to a target molecule (e.g., DNA-bound chemical). 

After absorption many xenobiotics enter some kind of depot (e.g. adipose tissue, bone tissue, certain proteins or some other tissue components) and are thus excluded from playing a part in leveling the transport gradients. This means that further absorption will take place and the overall levels of the envirotoxicant in the organisms will increase. 

Not all stereoselectivity seen with enantiomers can be attributed tc differences In reactivity at the receptcr site. Differences In biological activity also can result frcm differences In the ability of each enanticmer tc reach the receptcr site. Because the biological system encountered by the drug Is asymmetric, each enantiomer may experience selective penetration of membranes, metabolism, and absorption at sites of loss (e.g., adipose tissue) or excretion. Figure 2.20 shows the selective phases that enantiomers may encounter before reaching the receptor. Not all of these processes may be encountered by a particular enantiomer, but such processes may... 

Distribution. Oganochlorines are found in the liver, kidney, and brain they rapidly accumulate in lipid depots (e.g., adipose tissue). 

Tissues which are more active in the synthesis of lipids than nucleotides require NADPH rather than ribose moieties. In such tissues, e.g. adipose tissue, the ribose 5-phosphate enters a series of sugar interconversion reactions which connect the pentose phosphate pathway with glycolysis and gluconeogenesis. These interconversion reactions constitute the non-oxidative phase of the pathway (Figure 11.14) and since oxidation is not involved, NADPH is not produced. Two enzymes catalyse the important reactions transketolase which contains thiamin diphosphate (Figure 12.3a) as its prosthetic group and transaldolase. Both enzymes function in the transfer of carbon units transketolase transfers two-carbon units and transaldolase transfers three-carbon units. The transfer always occurs from a ketose donor to an aldose acceptor. The interconversion sequence requires the oxidative phase to operate three times, i.e. three molecules of glucose 6-phosphate yield three molecules of ribulose 5-phosphate. 

Organs and tissues performing functions such as storage (e.g. adipose tissue), chemical processing (e.g. liver), mechanical work (e.g. muscle) and excretion (e.g. kidney) tend to have membranes in which the n-6 fatty acids... 

The GI absorption of the dmg after po adrninistration is slow and variable with estimates ranging from 20—55%. Once absorbed, 96% of the dmg is bound to plasma proteins and other tissues on the body. Whereas peak plasma concentrations may be achieved in 3—7 h, the onset of antiarrhythmic action may occur in 2—3 days or more. This may result, in part, from distribution to and concentration of the dmg in adipose tissue, Hver, spleen, and lungs. Therapeutic plasma concentrations are 1—2 p.g/mL, although there appears to be no correlation between plasma concentration and antiarrhythmic activity. The plasma half-life after discontinuation of the dmg varies from 13—103 days. The dmg is metabolized in the Hver and the principal metaboHte is desethylamiodarone. The primary route of elimination is through the bile. Less than 1% of the unchanged dmg is excreted in the urine. The dmg can also be eliminated in breast milk and through the skin (1,2). 

The method of choice for the determination of a- and P-endosulfan in blood, urine, liver, kidney, brain, and adipose tissue is gas chromatography equipped with an electron capture detector (GC/ECD) (Coutselinis et al. 1976 Demeter and Heyndrickx 1979 Demeter et al. 1977 Le Bel and Williams 1986). This is because GC/ECD is relatively inexpensive, simple to operate, and offers a high sensitivity for halogens (Griffith and Blanke 1974). After fractionation of adipose tissue extracts using gel permeation chromatography, detection limits of low-ppb (1.2 ng/g) were achieved for endosulfan and other chlorinated pesticides using GC/ECD (Le Bel and Williams 1986). 

Figure 22.1 A. Schema for a physiologically based pharmacokinetic model incorporating absorption in the stomach and intestines and distribntion to various tissues. B. Each organ or tissue type includes representation of perfusion (Q) and drug concentrations entering and leaving the tissue. Fluxes are computed by the product of an appropriate rate law, and permeable surface area accounts for the affinity (e.g., lipophilic drugs absorbing more readily into adipose tissue). Clearance is computed for each tissue based on physiology and is often assumed to be zero for tissues other than the gut, the liver, and the kidneys.

Intravenous lipid emulsion particles are hydrolyzed in the bloodstream by the enzyme lipoprotein lipase to release free fatty acids and glycerol. Free fatty acids then are be taken up into adipose tissue for storage (triglycerides), oxidized to energy in various tissues (e.g., skeletal muscle), or recycled in the liver to make lipoproteins. 

A triaryl phosphate ester, tributoxyethyl phosphate, was detected at a mean concentration of 11.3 ng/g in 41 of 115 human adipose tissue samples taken from cadavers from Kingston and Ottawa, Canada (LeBel and Williams 1986). Because triaryl phosphate esters have been found in Canadian drinking water and... 

Human adipose tissue Homogenization solvent extraction GPC and Florisil column clean-up Capillary GC/NPD confirmation by GC/MS Low ng/g 69-104% LeBel and Williams 1983... 

Hardell L, Carlberg M, Hardell K, Bjomfoth H, Wickbom G, Ionescu M, van-Bavel B, Lindstrom G (2007) Decreased survival in pancreatic cancer patients with high concentrations of organochlorines in adipose tissue. Biomed Pharmacother 61 (10) 659-664. doi 10.1016/j.biopha.2007.04.006... 

A wet-ashing procedure for analysis of fatty animal tissue was modified by using Teflon-lined bombs rated for use at 340 bar instead of open crucibles. Bombs cooled to well below 0°C were charged with fuming nitric and fuming sulfuric acids (1 ml of each) and adipose tissue (0.5 g), removed from the cooling bath and sealed. After 10 min delay, the bombs exploded, probably owing to development of... 

Beta-1, beta-2, and beta-3 adrenergic receptors are G-protein-coupled receptors. Beta-1 and beta-2 receptors mediate the positive inotropic, chronotropic, and dro-motropic effects of the endogenous catecholamines epinephrine and norepinephrine. The beta-3 subtype seems to play a role in regulating thermogenesis and lipid mobilization in brown and white adipose tissue. Several coding and promoter polymorphisms of these receptors have been identified. Clinical studies in asthma... 

A1 adenosine receptors are inhibitory in the central nervous system. A receptors were originally characterized on the basis of their ability to inhibit adenylyl cyclase in adipose tissue. A number of other G-protein-mediated effectors of A receptors have subsequently been discovered these include activation of K+ channels, extensively characterized in striatal neurons [13], and inhibition of Ca2+ channels, extensively characterized in dorsal root ganglion cells [14]. Activation of A receptors has been shown to produce a species-dependent stimulation or inhibition of the phosphatidylinositol pathway in cerebral cortex. In other tissues, activation of A receptors results in synergistic activation of the phosphatidylinositol pathway in concert with Ca2+-mobilizing hormones or neurotransmitters [15]. The effectors of A adenosine receptors and other purinergic receptor subtypes are summarized in Table 17-2. 

---