EROL activity

Keywords Ab initio computations AhR-mediated toxicity Algebraic norm Carcinogenity Chemical hardness Conceptual DPT Electronegativity EROL activity Logistic enzyme kinetics Pimephales promelas QSAR Rats Toxicity... 

No unequivocal unique function for vitamin E has been defined. However, it does act as a hpid-soluble antioxidant in cell membranes, where many of its functions can be provided by synthetic antioxidants. Vitamin E is the generic descriptor for two famihes of compounds, the tocopherols and the tocotrienols (Figure 45—5). The different vitamers (compounds having similar vitamin activity) have different biologic potencies the most active is D-a-tocopherol, and it is usual to express vitamin E intake in milhgrams of D-a-tocoph-erol equivalents. Synthetic DL-a-tocopherol does not have the same biologic potency as the namrally occurring compound. 

H linked intracellular messengers. Activated H receptors are known to activate a pertussis-toxin-insensitive G protein, Gq, that stimulates phosphoinositide-specific phospholipase C (PI-PLC), with the subsequent generation of inositol 1,4,5-trisphosphate (IP3) and diacylglyc-erol (DAG). These two mediators are known to elevate intracellular Ca2+ concentrations and to activate PKC,... 

All muscarinic receptors are members of the seven transmembrane domain, G protein-coupled receptors, and they are structurally and functionally unrelated to nicotinic ACh receptors. Activation of muscarinic receptors by an agonist triggers the release of an intracellular G-protein complex that can specifically activate one or more signal transduction pathways. Fortunately, the cellular responses elicited by odd- versus even-numbered receptor subtypes can be conveniently distinguished. Activation of Ml, M3, and M5 receptors produces an inosine triphosphate (IP3) mediated release of intracellular calcium, the release of diacylglyc-erol (which can activate protein kinase C), and stimulation of adenylyl cyclase. These receptors are primarily responsible for activating calcium-dependent responses, such as secretion by glands and the contraction of smooth muscle. 

The plasma lipoproteins include chylomicrons, very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). They function to keep lipids (primarily triacylglyc-erol and cholesteryl esters) soluble as they transport them between tissues. Lipoproteins are composed of a neutral lipid core (containing triacylglycerol, cholesteryl esters, or both) surrounded by a shell of amphipathic apolipoproteins, phospholipid, and nonesterified cholesterol. Chylomicrons are assembled in intestinal mucosal cells from dietary lipids (primarily, triacylglycerol) plus additional lipids synthesized in these cells. Each nascent chylomicron particle has one molecule of apolipoprotein B-48 (apo B-48). They are released from the cells into the lymphatic system and travel to the blood, where they receive apo C-ll and apo E from HDLs, thus making the chylomicrons functional. Apo C-ll activates lipoprotein lipase, which degrades the... 

Most membrane receptors generate a diffusible intracellular signal called a second messenger. Five intracellular messengers are currently known Cyclic AMP, cyclic GMP, inositol triphosphate, diacylglyc-erol, and calcium. Second messengers usually activate or inhibit the action of one or more enzymes. 

Hyperlipidemia (mainly hypercholesterolemia) is a regular part of nephrotic syndrome (K13, W6). Serum levels of cholesterol are often markedly elevated, usually above 10 mmol/L. However, in severely malnourished patients, normal or even decreased serum cholesterol level can be found. Serum levels of triacylglyc-erols fluctuate, from normal values to markedly elevated values (mainly in patients with proteinuria higher than 10 g/24 hr). There is a variable increase in plasma concentrations of very low density lipoproteins (VLDL, they correlate negatively with serum albumin level), intermediate-density lipoproteins (IDL), andLDL however, plasma concentrations of HDL are usually normal (J3). Levels of lipoprotein(a) [Lp(a)j are also increased (W4). Remission of nephrotic syndrome or decrease of proteinuria may result in the decrease of plasma concentrations of Lp(a) (G2). Concentration of free fatty acids in serum is commonly decreased because they are normally bound to albumin and albumin is lost into the urine. The activity of lecithin cholesterol acyltransferase (LCAT) is usually decreased. 

Leucetta leptorhapsis, the Antarctic rubber sponge, so called due to its stretched appearance, produces the acetogenin rhapsamine (Structure 7.22), which bears the unusual bis(l,3-diaminoglyc-erol) group.39 Rhapsamine has antipredatory and cytotoxic activity and is structurally related to the coriacenins, which are produced by the Mediterranean sponge Clathria coriacea.104... 

Activation of phospholipase Cp (Figure 8.2c). This enzyme is associated with the iimer surface of the plasma membrane and splits the phospholipid phosphatidylinositol4,5-bisphosphate into diacylglyc-erol (DAG) and inositol-1,4,5-triphosphate (IP3). Dia-cylglycerol is hydrophobic and remains associated with the membrane, where it will activate protein kinase C, which in turn will activate a broad and cell-dependent spectrum of target proteins. IP3 is water-soluble and... 

Ergocalciferol is derived from ergosterol in the diet. Colecalciferol is derived from endogenous cholesterol. Both are also synthesized in the skin. Colecalciferol and ergocalciferol are converted in the liver by hydroxylation to calcifediol, which is weakly active. Calcifediol is activated in the kidneys by further hydroxylation to alfacalcidol, which is highly active, and calcitriol, which is weakly active. Calcitriol is deactivated by further hydroxylation in the kidney to 1 a,24,25-trihydroxycolecalcif erol. 

A cholesterol precursor may be converted to 1,25-dihydroxycholecalcif-erol, the active form of vitamin D3. 

C. Reduction of HMG CoA to mevalonic acid is an early step in cholesterol synthesis. Inhibition of this step would lead to an increase in cellular levels of HMG CoA and a decrease in squalene, an intermediate beyond this step, and cholesterol. The decreased cholesterol levels in cells cause ACAT activity to decrease and synthesis of LDL receptors to increase. Because the receptors function (but at a less than normal rate), more receptors cause more LDL to be taken up from the blood. Consequently, blood cholesterol levels decrease, but blood triacylglyc-erol levels do not change much, since LDL does not contain much triacylglycerol. 

The 25-hydroxylated product is then transported to the kidney where it is hydroxylated a second time by 25(OH)D-l a-hydroxylase, forming the active 1,25-dihydroxycholecalcif-erol [1,25(0H)2D3]. The latter is transported to the intestinal tract, where it attaches to a nuclear receptor that signals the mucosa cell... 

The efficient formation of disulfide bonds In the lumen of the ER depends on the enzyme protein disulfide isomerase (PDI), which Is present In all eukaryotic cells. This enzyme Is especially abundant In the ER of secretory cells In such organs as the liver and pancreas, where large quantities of proteins that contain disulfide bonds are produced. As shown in Figure 16-19a, the disulfide bond in the active site of PDI can be readily transferred to a protein by two sequential thiol-disulfide transfer reactions. The reduced PDI generated by this reaction is returned to an oxidized form by the action of an ER-resident protein, called Erol, which carries a disulfide bond that can be transferred to PDI. It is not yet understood how Erol itself becomes oxidized. Figure 16-20 depicts the organization of the pathway for protein disulfide-bond formation In the ER lumen and the analogous pathway In bacteria. 

Tocopherol. 3,4.Dihy,H-tritn thyt-2-(4,8,12.trimethyitridecyl)-2II-l-benzopyran-0-ol-, 2,5,8-tri-methy/-2-(4,8.12-trimethyltridecyl i-6-chro manol 5.8-di-methyltocol cumotocopherol neotocopherol p-xylotocoph-erol. CjjHjjOji mol wt 416.66. C 80.71%, H 11-61%,. O 7.68%. Accompanies vitamin E (-copherol from natural sources. Is biologically less active than a-tocopherol. May be separated by fractional crystn of the allophanates Emerson er aL, Science 83, 421 (1936) J. Biol. Chem. 113, 319 (1936) Baxter et aL, J, Am, Chem. Soc. 65, 918 (1943). 

Regulation in bone uses exon 1.6 (ref. [1303]). The study of regulation in bone is less extensive than in other sites, and 1,25-dihydroxycholecalcif-erol, interleukins, TNFa, and TGF-p, have had stimulatory activity. 

Hopia, A.I., Hnang, S.W., Schwarz, K., German, B., and Frankel E.N., Effect of different hpid systems on antioxidant activity of rosemary constituents. Camosol and camosoic acid with and without a-tocoph-erol, J. Agric. Food Chem., 44, 2030, 1996. 

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