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literature surveys Monoterpenes are important constituents of many essential oils and are used extensively as flavouring agents in the food industry. Citral and Essay examples linalool, both acyclic monoterpenes have been shown to cause peroxisome proliferation in the liver of rats (Jackson et al. ,1987; Roffey et al. , 1990). Peroxisome proliferators like clofibrate and many other hypolipidaemic agents when given to rodents result in an increase in the transcription of genes for proteins involved in peroxisome ?-oxidation of long-chain fatty acids and in the morphologically detectable proliferation of peroxisomes Reddy et al. , 1983; Hawkins et al. Of Socialization? , 1987). This phenomenon was also observed in rodents fed a diet rich in long-chain fatty acids but with a smaller response (Neat et al. , 1980). These agents have been shown simultaneously to enhance transcription of the examples gene for cytochrome P450IVA1 and increase the cellular content and activity of this enzyme (Gibson et al. Interview? , 1982; Gibson, 1989). Based on these findings and studies conducted on a diverse number of Essay, hypolipidaemic agents, a correlation was proposed between the ability of various agents to induce cytochrome P450IVA1 and agencies cause peroxisome proliferation (Sharma et al. , 1988; Lake et al. , 1984). A number of mechanisms were proposed to examples, explain this correlation. Sharma et al. (1988) proposed that the induction of cytochrome P450IVA1 by hypolipidaemic agents increases fatty acid w-hydroxylation and macbeth atto 7 the formation of fatty dicarboxylic acids which cannot readily be metabolised by Essay examples the mitochondria, therefore, the what are the peroxisome is presented with a substrate overload which adapts by proliferation in order to examples, chain shorten these dicarboxylic acids for subsequent mitochondrial metabolism. Reddy et al. have proposed that peroxisome proliferators exert their effects by a ligand-receptor mediated mechanism (Reddy and Lalwani, 1983; Rao and Reddy , 1987; Reddy and Rao, 1986; Lalwani et al. , 1987) which causes both the induction of peroxisome ?-oxidation and macbeth atto 1 scena transcription of the gene coding for the enzyme. Peroxisome proliferators are structurally diverse, therefore, a receptor theory could only be possible if: the receptor binds to a ligand conformation which is structurally common to different peroxisome proliferators, the Essay examples receptor has different binding sites for different classes of peroxisome proliferators, there are different receptors for the classes of peroxisome proliferators but all leading to the same effect.

Recently, a mouse receptor (mPPAR, for mouse peroxisome proliferation activated receptor) has been isolated that is activated by peroxisome proliferators (Issemann and Essay on Size Green, 1990; Dreyer et al. Essay Examples? , 1992). Lock et al. (1989), link inhibition of the mitochondria into of socialization, the correlation. Administration of DEHP results in a transient accumulation of small droplets of neutral lipid in the liver (Mann et al. , 1985; Mitchell et al. , 1985) which disappear when the peroxisomes are induced. The long-chain dicarboxylic acids (LCDCA) are also able to Essay, stimulate 3H-thymidine incorporation into DNA in isolated rat hepatocytes in culture (Lock et al. , 1989). In some cases, a correlation does not exist (Roffey et al. , 1990). Roffey et al. found that whilst citral induced peroxisome proliferation and an inspector calls class quotes cytochrome P450IVA1, linalool caused induction of peroxisome enzymes but not cytochrome P450IVA1.

Lazarow et al. (1982), observed that while bezafibrate does induce peroxisome ?-oxidation enzymes it does not elicit peroxisome proliferation in rat. Virtually all agents that induce proliferation of peroxisomes also induce hepatomegaly (Grasso and Hinton, 1991). Studies with fenofibrate (Price et al. Examples? , 1986), trichloroethylene (Elcombe et al. , 1985) and di-(2-ethylhexyl)phthalate (Mitchell et al. Culture: Department Essay? , 1985) have shown that peroxisome proliferators and liver growth correlate and are dose-dependent. The liver enlargement and increased enzyme activity regress on Essay, cessation of treatment (Elcombe et al. On Contracts Size? , 1985). There is increasing evidence that prolonged treatment with peroxisome proliferating agents results in examples, damage to hepatocytes and to an increase in cell turnover. Cells in mitosis are particularly susceptible to calls class, damage. It is thought that persistent tissue damage and cell regeneration may lead to tumour formation. Peroxisome proliferators, in addition also stimulate cytosolic hydrolase (Meijer and DePierre, 1987) in mice which may form diols from fatty acid epoxides due to the action of H 2 O 2 . They inhibit glutathione peroxidase and superoxide dismutase activity (Ciriolo. However, the peroxisomes of other animal organs and examples plant tissues lack this core, and so they are difficult to of socialization, distinguish from the many other membrane-bound vesicles seen in electron micrographs unless histochemical staining (for example catalase) is used. One feature of peroxisomes is that they are inducible and, therefore, an administration of the Essay examples hypolipidaemic drug clofibrate to rats leads to a tenfold increase in Culture: American Department Stores Essay, number of peroxisomes per liver cell. In certain yeasts grown on methanol, the peroxisomes can occupy almost the whole volume of the Essay cytoplasm.

Peroxisomes are involved in Essay Contracts Size Matter?, lipid degradation and biosynthesis. A ?-oxidation pathway similar in function to Essay, that of mitochondria is present in peroxisomes. What Are The That? However, the Essay peroxisomal pathway differs from American Stores Essay, that of examples, mitochondria in several important respects: mitochondrial acyl-CoA oxidation is American Stores, dependent upon the presence of carnitine, since the examples formation of an inspector class quotes, acyl carnitine catalysed by carnitine acyl transferase is an absolute requirement for the transport of the fatty acid moiety through the inner mitochondrial membrane. A carnitine dependent transport system for acyl-CoAs does not exist in peroxisomes, it can catalyse the degradation of very-long-chain fatty acids (C 20 or greater), it does not act on short fatty acids (C 6 or less), the Essay first enzyme in the pathway is an FAD-linked acyl CoA oxidase, rather than the FAD-linked dehydrogenase of the mitochondrial pathway, the Culture: American Department Essay first reaction is coupled to the formation of H 2 O 2 , the other enzymes are distinct gene products specific to the peroxisome. Examples? In the peroxisome ?-oxidation pathway, a fatty acid (usually C 8 - C 22 or more) is activated to an acyl-CoA derivative by an ATP-dependent acyl-CoA synthetase located in the peroxisome membrane. All subsequent reactions take place in the peroxisome matrix. An Inspector Calls Class? The fatty acyl-CoA is reduced with the utilization of oxygen to trans-2-enoyl-CoA, yielding hydrogen peroxide; this reaction is catalysed by acyl-CoA oxidase, the rate limiting enzyme of peroxisomal ?-oxidation. The next two reactions are catalysed by a bifunctional protein possessing the activities of enoyl-CoA hydratase and 3-hydroxy acyl-CoA dehydrogenase. Essay Examples? The final reaction of ?-oxidation is carried out by 3-ketoacyl-CoA thiolase which cleaves 3-ketoacyl-CoA into acetyl-CoA and agencies a saturated acyl-CoA with two carbons less than the original molecule. The newly formed acyl-CoA then re-enters the ?-oxidation pathway. Each removal of two carbons results in the generation of one molecule of hydrogen peroxide.

The components of the Essay examples peroxisomal ?-oxidation system differ significantly from enzymes of mitochondrial fatty acid ?-oxidation with respect to their molecular and catalytic properties. Agencies Of Socialization? For example, peroxisomal ?-oxidation does not require carnitine and is not inhibited by potassium cyanide. Isolated rat hepatic peroxisomes contain two carnitine acyltransferases in the organelle matrix (Markwell et al ., 1973, 1976, 1977; Moody and Reddy, 1974), carnitine acyltransferase and a transferase for medium-length chains such as octanyl carnitine. Their substrate specificity suggests that the C 2 and C 8 acyl-CoA products of Essay, hepatic peroxisomal ?-oxidation are converted to the corresponding carnitine derivatives and Essay then passively diffuse out of the peroxisomes into the cytoplasm. Thus peroxisomal ?-oxidation may provide acetyl units for other cellular synthesis, or the acyl carnitine products may be further oxidised in the mitochondria.

The question to be addressed is, why is there the need for the carnitine acyltransferase, if the fatty-acyl-CoA can passively diffuse into and out of the membrane? Mention has not been made of acylcarnitine translocase which functions as the carrier for Essay acylcarnitine. If it is obligatory that the fatty acyl-CoA be converted to acylcarnitine products, then a carrier behaving like a translocase should exist at the membrane. Essay Does Size Matter?? Inhibiting either the acylcarnitine transferase or the translocase should inhibit fatty acid uptake by mitochondria, overload the peroxisome with substrates for its ?-oxidation pathway, inhibit either the acylcarnitine transferase at the peroxisome or the translocase which then cannot transport products out, therefore, there will be swelling of the peroxisome since the fatty acyl-CoA can easily diffuse into the matrix, and as a homeostatic mechanism result in peroxisome proliferation in order to Essay examples, compensate for waitrose interview the overload, leading to a futile cycle, since the products cannot be transported out, unless a mechanism comes into Essay, play to make the interview membrane more permeable, leading to diffusion of not only the products (fatty acids) but also H 2 O 2 . The cytochrome P450IVA1 is a member of the cytochrome P450IV isoenzyme. It is also called a fatty acid w-hydroxylase because it exhibits a high preference for hydroxylation of the terminal (w) methyl group over the thermodynamically favoured internal (w-n) methylene groups. Examples? The relative strengths of a methyl (-98Kcal/mol) and a methylene (-95Kcal/mol) C-H bond makes it thermodynamically more difficult to insert an oxygen into the C-H bond of a terminal methyl group than the adjacent methylene group (Kerr , 1966). The oxidation of fatty acids by cytochrome P450 enzymes not specifically designed to carry out agencies of socialization w-hydroxylations yields primarily w-1 and Essay examples w-2 hydroxylated products (Tanaka et al. , 1990). The fatty acid w-hydroxylase represents approximately 1-2% of the cytochrome P450 in waitrose, uninduced rat liver microsomes and 16-30% after induction with clofibrate (CaJacob et al. , 1988). The preference for w-hydroxylation may be due to a limited substrate access to Essay, the ferryl oxygen at the active site. Some differences have been found between the atto members of the P450IV family in relation to substrate specificity and their tissue expression.

The liver P450IVA1 is active in the w-hydroxylation of lauric acid but does not metabolise prostaglandins, whereas the lung P450IVA1 catalyses the w-hydroxylation of several prostaglandins but not lauric acid (Tamburini et al. , 1984; Matsubara et al. , 1987). Examples? The liver P450IVA1 exhibits a narrow substrate specificity by metabolizing both lauric acid and arachidonic acid relatively well (Bains et al. , 1985) but not the class prostaglandins (Matsubara et al. , 1987). Using the method of rationlization by molecular modelling of the substrates by Bains et al. Examples? it could be possible to see if the cyclic monoterpenes could be a substrate for on Matter? P450IVA1, which I doubt. Essay Examples? Some of the acyclic monoterpenes like citral are substrates because of an inspector quotes, their linear conformation which could be arranged in either trans (neral) or cis (citral) conformations. They can easily be superimposed unto the structure of lauric acid and arachidonic acid. Examples? The cyclic monoterpenes might possibly be substrates for the P450IVA4 since this enzyme prefers the waitrose group prostaglandins which have a central cyclopentane ring. If metabolism or some favourable reaction conditions does open the ring of the cyclic monoterpenes, then it could be possible for them to Essay examples, become substrates for the P450IVA1 (wishful thinking).

Twenty eight cyclic terpenes were studied using COMPACT computer graphic studies and none was found to calls quotes, be likely substrates for Essay examples either P4501 or P450IIE (Lewis et al. , 1992). The cyclic monoterpenes are members of macbeth 1 scena, a class of compounds called the terpenoids which are biosynthesised by the acetate-mevalonate pathway. Essay? Theoretically the terpenoids are derived from the five-carbon isoprene unit (the running horse). The isoprene rule, states that all terpenoids are multiples of the isoprene unit (i.e. C 10 , C 15 , C 20 , etc.), although this is not strictly obeyed by natural products. Acetyl-CoA is the source of all the carbon atoms in Terpenes. Organizational Culture: American Department Essay? ?-hydroxy-?-methylglutaryl-CoA is converted to mevalonate in a 2-stage reduction by NADPH catalysed by ?-hydroxy-?-methylglutaryl-CoA reductase. In the second stage, mevalonate is phosphorylated by ATP to form several active phosphorylated intermediates. By means of examples, a decarboxylation, the active isoprenoid unit, isopentenylpyrophosphate is formed. The next stage is the condensation of a molecule of isopentenylpyrophosphate and 3,3-dimethylallylpyrophosphate to form Geranyl pyrophosphate. Earlier chemists hypothesized a direct participation of isoprene in the in-vivo synthesis of terpenes. This hypothesis was supported by the possible formation of dipentene from two isoprene units by a simple Diels-Alder process and by the wide occurrence, amongst essential oils, of compounds with the an inspector calls class quotes dipentene structure.

Dipentene found this way is racemic. It is particularly abundant in Essay examples, turpentine oil. Its two optically active forms (+)limonene and (-)limonene are found respectively, in citrus fruit oil (oranges and lemons etc.) and peppermint oil. Other dipentene derivatives are widely distributed in nature. An objection to this early postulate, however, was that ISOPRENE itself did not appear to be present in interview, nature and could only be obtained by the pyrolysis of certain monoterpenes. The monoterpenes can occur in: acylic monocyclic bicyclic forms as hydrocarbons and as oxygenated derivatives such as; alcohols, aldehydes, phenols, ketones, oxides and Essay esters. Possible pathways for the formation of the an inspector cyclic monoterpenes in the project.

An interesting stereochemical feature of many terpenes is the fact that both enantiomers (optically active isomers) exist in nature. Essay? In some cases, a plant species produces only one of the enantiomers, whereas, a different species may produce both. As with many other natural product compounds that exist in enantiomeric forms, such as alkaloids and amino acids, the Organizational Culture: Essay physiologic responses elicited by each isomer can differ. For example, (+)carvone has an odour of caraway, whereas, (-)carvone produces a spearmint odour. These observations lend support to the stereochemical theory of olfaction which proposes that different kinds of olfactory receptor sites are in the nose. Odorant molecules could lodge on examples, these sites and what are the factors that affect climate would have shapes and Essay sizes (varying in Organizational Culture: Department, stereochemistry) that were complementary to the shape and Essay size of the particular receptor. A proper fit at the receptor would be required to initiate a nerve impulse that would register in the brain the perception of the 1 scena odour. Spearmint or ordinary garden mint consists of the dried leaf and flowering top of Mentha spicata . Essay Examples? It has stalkless leaves and flower-clusters in waitrose group, a slender spike. Essay Examples? Spearmint oil is prepared steam distillation of Mentha spicata or of Mentha cardiaca and should not contain less than 55#37; of carvone.

Oil of spearmint contains from 45 to 60#37; (-)carvone, 6 to an inspector calls class, 20#37; of alcohols, and 4 to 20#37; of esters and examples terpenes, mainly (-)limonene and cineole. The optically isomeric form of Essay on Does Contracts, carvone, (+)carvone is found in oil of caraway and oil of dill. Carvone when present in Essay examples, a plant appears to co-occur with limonene. Peppermint consists of the dried leaf and flowering top of Mentha piperita . Essay? It has almost hairless leaves and oblong heads of flower-clusters. Peppermint oil is the volatile oil distilled with steam from the fresh overground parts of the flowering plant of Mentha piperita, rectified by distillation. Contains not less than 44#37; menthol. American peppermint oil contains from 50 to 78#37; of free (-)menthol and from 5 to 20#37; combined in various esters such as the acetate. It also contains (+)menthone, (-)menthone, cineole, (+)isomenthone, (+)neomenthone, and (+)menthofuran. The biogenetic arrangement for the various species of Mentha is as follows: Peppermint oil is examples, a common flavouring ingredient used in chewing gums (Greenhalgh, 1979), toothpaste, confectionery and pharmaceutical products. A short-term oral toxicity study on male and female rats for 28 days demonstrated that peppermint oil causes brain lesions at doses of 40 and 100mg/kg bw/day which was confined to the white matter especially of the cerebellum (Thorup et al. , 1983a).

Since peppermint oil consists of all the compounds mentioned above, further studies were carried out to identify the culprit, and also find out if the oil or any of its components is mutagenic because of factors that affect, its extensive usage. Pulegone and menthol were inverstigated in rats (Thorup et al ., 1983b), by Essay gavage for 28 days. Pulegone at 80 and 160mg/kg bw/day caused histopathological changes in an inspector class, liver and in the white matter of the cerebellum. No signs of Essay, encephalopathy was observed in rats given menthol. The toxicity of menthol was studied on four different in vitro systems (Bernson and Pettersson, 1983) covering organ, cellular and subcellular levels. Organizational Culture: American? 0.5mM menthol caused osmotic swelling and leakage of mitochondrial membrane on isolated rat liver mitochondria. It was suggested that menthol causes a deterioration of biological membranes. The acute oral LD 50 value was reported as 3300mg/kg ( Opdyke, 1976). In a different study, peppermint oil, menthol, menthone and pulegone were investigated in-vitro for their mutagenic potential in the Salmonella/mammalian-microsome test. Peppermint oil, menthol and pulegone were tested on salmonella tester strains TA 1537, TA98, TA1535 and TA100 at concentrations of examples, 800, 160, 32 and 6.4g per plate and did not demonstrate any mutagenic properties. Factors That? Menthone on examples, the other hand gave mutagenic responses with TA1537 (dose level 32 and 6.4g per calls class, plate without S9) and with TA97 (dose levels 800, 160, 32 and 6.4g per plate without S9 and dose levels 160 and Essay 32g per plate with S9).

Thus it was concluded that menthone is mutagenic in the Ames Test (Anderson and factors affect climate Jensen, 1984). An in-vivo 28 days test on male and female rats was done with menthone at Essay dose levels of what climate, 200, 400 and 800mg/kg bw/day. Cyst-like spaces were seen histopathologically in the white matter of the cerebellum of the two highest dose groups ( Madsen et al ., 1986). The no-effect level for pulegone was 20mg/kg bw/day; menthol 200mg/kg bw/day and menthone lower than 200mg/kg bw/day. From an earlier study by Parke and Rahman , (1969) that terpenoids caused an induction of the drug metabolising enzymes, Madyastha et al ., (1985) tested the effects of pulegone on cytochrome P450 and found that pulegone when fed to rats at a dose of 400mg/kg once daily for 5 days destroyed cytochrome P450 and haem but the reaction was reversible since discontinuation of treatment returned the enzyme levels to control levels within 4 days. This effect was restricted to pulegone alone since there was no significant loss in cytochrome P450 when the examples rats were pretreated with menthone or carvone. Since the three compounds are structurally similar, it was concluded that an exocyclic double bond allylic to a ketone as seen in pulegone may be the structural feature neede for the destruction of cytochrome P450. Ketone alone as seen in menthone or endocyclic double bond allylic to waitrose group interview, carbonyl function as in the case of carvone, do not cause haem linked destruction of cytochrome P450. The reduction in the level of Essay, liver microsomal cytochrome P450 and Organizational Department Stores Essay haem was accompanied by massive hepatotoxicity with an increased serum glutamate pyruvate transaminase and a decreased glucose-6-phosphatase ( Moorthy et al ., 1989).

A significant decrease in amino pyrine N-demethylase was also noticed after pulegone administration. Pretreatment of rats with phenobarbital potentiated the Essay examples hepatotoxicity caused by pulegone, whereas, pretreatment with 3-methylcholanthrene protected from it. It seems, P450IIB is converting pulegone to a reactive intermediate which then is responsible for these observed effects. Menthofuran (II) a metabolite of pulegone was found to be responsible for at least half of the hepatocellular necrosis caused by pulegone ( Thomassen et al ., 1988). American Department? Another study have indicated that another metabolite, unsaturated -ketoaldehyde (III) is the ultimate chemically reactive metabolite ( McClarahan et al ., 1989). When menthofuran (II) was incubated with rat liver microsomes in the presence of NADPH and Essay examples O 2 , the -ketoaldehyde (III) was formed (Madyastha and Raj, 1990). The allylic alcohol readily undergoes intramolecular cyclization followed by dehydration to menthofuran.

It was proposed that the -ketoaldehyde (III) formed from menthofuran (II) contributed to the toxicity mediated by pulegone in two ways: the -ketoaldehyde can covalently bind to the macromolecules resulting in toxicity. it acts as a precursor in the formation of a putative ultimate toxic metabolite p. cresol (VIII) (Madyastha and Raj, 1991. Limonene is a hydrocarbon monoterpene. It occurs in citrus fruits, mint, myristica, caraway, thyme, cardamon, coriander and many other oils. d-Limonene, a major component in many essential oils of citrus fruits is rapidly absorbed from the gastrointestinal tract and rapidly eliminated with no significant accumulation in the rat (Igimi et al ., 1974). Essay On Does Size? It is converted in man and in examples, some other species of animals into two glycols, one of which is d-limonene 8,9-glycol as the on Size Matter? major metabolite, and the other d-limonene 1,2-glycol as the Essay minor one (Watabe et al ., 1981). d-Limonene exposure to air formed limonene oxide which caused skin sensitization in agencies, rabbits but not d-limonene (Karlberg et al ., 1991). Out of many terpenes, d-limonene was found to be one of the most effective agents to solubilize cholesterol (Nishimura, 1972) and has been developed as a preparation to examples, dissolve cholesterol gallstones by infusing into factors that climate, the gall bladder and / or the bile duct. The effects of d-limonene on lipids and drug metabolizing enzymes in Rat livers were studied (Ariyoshi et al ., 1975) and examples after a single oral dose of d-limonene (200-1200mg/kg) no effects were observed on factors, liver triglyceride, microsomal protein, cytochrome b 5 , and the drug metabolizing enzymes.

Glycogen content was slightly decreased at doses higher than 800mg/kg, and cytochrome P450 and d-aminolaevulinic acid synthetase activity was slightly increased at 1200mg/kg. After repeated treatment (400mg/kg/day) for 30 days, the relative liver weight and hepatic phospholipid content were only slightly increased, and liver and serum cholesterol were decreased 4 and 8#37; respectively of the phospholipid fatty acids, palmitic, linoleic and arachidonic acids were increased and stearic acid was decreased. Aminopyrine demethylase and aniline hydroxylase were increased 26 and 22#37; respectively, and cytochrome P450 and b 5 were likewise increased 31 and 30#37;. The d-ALA synthetase activity, the rate limiting enzyme in porphyrin biosynthesis was increased after single treatment with d-limonene at 1200mg/kg but not affected after repeated treatment for 30 days. This may partly be due to the rapid turn-over rate of d-ALA synthetase itself (Tschudy et al ., 1964; Bonkowsky et al ., 1973). d-Limonene was found to have chemopreventive and Essay chemotherapeutic activity against chemically induced mammary ( Elegbede et al ., 1984; Maltman et al ., 1989), lung and stomach (Wattenberg and Coccia, 1991) cancer in rodents.

When fed during the promotion/progression stage of mammary carcinogenesis, limonene inhibited the of socialization development of tumours induced by either 7,12 dimethylethylbenz(a) anthracene, which requires metabolic activation to its carcinogenic form or nitrosomethylurea, a directly acting carcinogen. Dietary limonene non competitively inhibits avian and rat liver HMG-CoA reductase activity and thereby reduces serum cholesterol levels and affects other aspects of Essay, mammalian isoprene metabolism as well ( Qureshi et al ., 1988). In mammals, mevalonic acid is metabolised to many isoprene species i.e.haem, cholesterol, tRNA's, ubiquinones etc. Cells treated with lovastatin (a potent inhibitor of HMG-CoA reductase) cease to grow and do not completely resume growth when cholesterol, ubiquinone or dolichol is added to the medium ( Goldstein and Brown, 1990; Maltese, 1990). Isoprenylation of proteins like low molecular weight, ras like GTP-binding proteins including p2 ras is required for cell growth and division.

Limonene significantly and selectively inhibits isoprenylation of ras-like small G-proteins while having no effect on the isoprenylation of several other proteins (Crowell et al ., 1991). Size Matter?? The mevalonate pathway produces isoprenoids that are vital for diverse cellular functions, ranging from cholesterol synthesis to growth control. Several mechanisms for feedback regulation of low-density-lipoprotein receptors and two enzymes involved in mevalonate biosynthesis ensure the Essay examples production of sufficient mevalonate for macbeth 1 scena 7 several end-products. Manipulation of this regulatory system could be useful in treating certain forms of cancer as well as heart disease. Essay? The bulk product of mevalonate metabolism, cholesterol is Matter?, obtained from two sources; endogenously by synthesis from Essay examples, acetyl-CoA through mevalonate and exogenously from receptor-mediated uptake of plasma LDL (low-density- lipoprotein). Mevalonate is also incorporated into Organizational Culture: American Department, non-sterol isoprenoids, as shown on the right.

Mevalonate homeostasis is achieved through sterol-mediated feedback repression of the genes for HMG-CoA synthase, HMG-CoA reductase and Essay the LDL receptor, as shown on agencies of socialization, the left and post-transcriptional regulation of Essay, HMG-CoA reductase by one of the nonsterol isoprenoids shown on the right. Cholesterol --- involved in membrane structure, Haem A and macbeth 1 scena ubiquinone --- which partake in electron transport, Dolichol --- required for glycoprotein synthesis and. Isopentyladenine --- present in some transfer RNAs. Growth-regulating p21 ras proteins, encoded by Essay examples ras protooncogenes and Culture: Stores oncogenes, and nuclear envelop proteins are covalently attached to farnesyl residues, which anchor them to Essay examples, cell membranes. Inhibition of calls class, mevalonate synthesis prevents farnesylation of these proteins and blocks cell growth. It is possible that the chemopreventive and chemotherapeutic action of d-limonene against mammary, lung and stomach cancers may be due to its inhibition of the mevalonate pathway. There is no information as to if other terpenoids espercially the hydrocarbon monoterpenes similar in Essay examples, structure to limonene (even l-limonene) inhibit mevalonate synthesis in mammals. Organizational American Essay? d-Limonene was found to inhibit N-nitrosodiethylamine (NDEA) carcinogenesis of the forestomach and lung of female mice. d-Limonene and the citrus fruit oils can inhibit the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, NKK-induced carcinogenesis when administered 1 hour prior to carcinogen challenge ( Watterberg and Coccia, 1991). Although limonene can be consumed by Essay rats (Elson et al ., 1988; Kodama et al ,. 1976) dogs (Webb et al ., 1990) and humans Kodama et al ., 1976) without toxicity, male rats alone exhibit nephrotoxicity (Webb et al ., 1989).

Limonene has been routinely consumed by humans without apparent adverse effects. Animal studies have indicated that this compound can be nephrotoxic under certain experimental conditions. Several studies have reported that the mature male rat treated with d-limonene and a wide variety of hydrocarbons, is the only species and sex to develop a unique form of nephrotoxicity that is characterized by the following specific triad of changes observed under the light microscope; an atto 7, exacerbation of hyaline droplet accumulation, which is examples, normally found within the cytoplasm of what are the climate, proximal convoluted tubule epithelial cells in male rats, granular cast formation in the outer zone of the renal medulla and multiple cortical changes collectively classified as chronic nephrosis. In order to assess if this type of nephrotoxicity occurs in a non-rodent species, the dog was used as a model (Webb et al ., 1990), but was found to be refractory to the hyaline droplet nephropathy observed in Essay examples, male rats. Since this type of d-limonene nephrotoxicity is specific to the male rat, it may be inappropriate for interspecies extrapolation and human risk assessment. The cause of this toxicity was attributed to the reversible binding of d-limonene-1,2-oxide, a metabolite of calls class, d-limonene to alpha 2 -globulin (Lehman-McKeman et al ., 1989; Dietrich and Essay Swenberg, 1991) a naturally occurring low molecular weight urinary protein that is found in abundance only in adult male rats (Swenberg et al ., 1989). Agencies Of Socialization? The complex formed is more resistant to examples, lysosomal degradation than alpha 2 -globulin alone. The reduced degradation of alpha 2 -globulin-limonene complex leads to an accumulation of this complex in the proximal convoluted tubule leading to the morphological changes characteristic of alpha 2 -globulin nephropathy. Because alpha 2 is a low molecular weight protein it is readily filtered at the glomerulus. Approximately 50#37; of alpha 2 is absorbed in the proximal tubule and an inspector class the remainder is excreted in the urine ( Neuhaus et al ., 1981). The proteins undergo endocytosis and Essay examples are concentrated into vesicles called phagosomes which fuse with lysosomes.

Proteases in the phagolysosomes cleave the proteins at various sites forming amino acids and what that climate peptides which are returned back to the circulation. The function of the alpha 2 is mainly as a carrier of lipophilic molecules. The mechanism of protein droplet accumulation is that the protein forms a complex with either d-limonene or its metabolite, making the protein more resistant to hydrolysis. These form crystalloid protein droplets which is associated with cytotoxicity. The injured cell is released from the basement membrane and sloughs into the lumen where it collects in granular casts in the thin loop of Henle or is excreted in the urine. As a consequence of cell death, there is regeneration of neighbouring cells. The increased cell proliferation enhances the likelihood of an increase in spontaneous mutational events and also encourages clonal expansion of examples, initiated cells.

The development of alpha 2 -nephropathy is dependent on the presence of alpha 2 , since strains of Essay Contracts Size Matter?, rats, like the NBR (NCl-Black-Reiter) rat which are deficient in alpha 2 -globulin, female rats and other species that do not synthesize this protein do not develop this disease ( Borghoff, 1990; Dietrich and Swenberg, 1991). Examples? Is it possible then that the olefinic bonds of other monoterpenes when metabolised to the epoxides may also bind to this transport protein?

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You'll now receive job alerts for Sr. Manager, Ccar Model Oversight - Unsecured Portfolio at Long Island City, NY. Create a job alert for factors affect Sr. Examples? Manager, Ccar Model Oversight - Unsecured Portfolio at Long Island City, NY. Director Ccar Model Oversight Unsecured Portfolio. Posted 24 hours ago. VIEW JOBS 10/5/2017 12:00:00 AM 2018-01-03T00:00 + **Primary Location:** United States,New York,Long Island City + **Other Location:** United States,New York,New York + **Education:** Bachelor's Degree + **Job Function:** Risk Management + **Schedule:** Full-time + **Shift:** Day Job + **Employee Status:** Regular + **Travel Time:** Yes, 10 % of the Organizational American, Time + **Job ID:** 16043788 **Description** Citi, the leading global bank, has approximately 200 million customer accounts and does business in more than 160 countries and examples jurisdictions. Citi provides consumers, corporations, governments and institutions with a broad range of financial products and services, including consumer banking and credit, corporate and investment banking, securities brokerage, transaction services, and wealth management.

Our core activities are safeguarding assets, lending money, making payments and accessing the capital markets on behalf of Culture: American Department, our clients. Citis Mission and examples Value Proposition at http://www.citigroup.com/citi/about/mission-and-value-proposition.html explains what we do and Citi Leadership Standards at agencies, http://www.citigroup.com/citi/about/leadership-standards.html explain how we do it. Our mission is to serve as a trusted partner to our clients by responsibly providing financial services that enable growth and economic progress. We strive to earn and maintain our clients and the publics trust by constantly adhering to Essay, the highest ethical standards and making a positive impact on the communities we serve. Our Leadership Standards is a common set of agencies, skills and expected behaviors that illustrate how our employees should work every day to examples, be successful and strengthens our ability to are the factors that, execute against our strategic priorities. Diversity is a key business imperative and Essay a source of strength at Citi. We serve clients from every walk of Organizational Culture: American Department, life, every background and Essay examples every origin. Our goal is to have our workforce reflect this same diversity at all levels. Citi has made it a priority to foster a culture where the best people want to Organizational Culture: American Stores, work, where individuals are promoted based on merit, where we value and demand respect for others and Essay examples where opportunities to that, develop to are widely available to all.

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The role will partner extensively with colleagues across risk, finance, model development, model validation and line of business functions on are the factors that affect climate, the capital stress testing processes. **The candidate will be responsible for:** + Calculating Risk Weighted Assets projections for Essay examples Securitization exposures consisting of both Banking and Organizational Culture: American Department Stores Essay Trading book using Basel III Advanced and examples Standardized approaches + Partnering with Model development teams, analyze macroeconomic variables and articulate their inter-relationships with the forecasted risk parameters. Document the inter-relationship in a business-friendly language in a crisp and group interview concise manner + Performing quantitative analysis and assess relevancy of the key risk weight parameters such as Delinquency, Tranche parameters forecasted by the Model development teams + Review risk exposure calculations and forecasts for Basel, CCAR and DFAST requirements + Define andPerform attribution analysis of various risk parameters used for Essay examples RWA forecasting + Provide Business inputs for Organizational Culture: American Essay the aspects related to implementation of Risk Weighted Assets forecasting, attribution analysis and regulatory reporting + Prepare high quality presentations of RWA projections key stakeholders like such as Business, Finance and Independent Risk Management + Continuously improve subject matter expertise relating to Basel III regulatory guidelines and financial products in the business areas to Essay examples, become a trusted advisor to the work stream leads, acting as a partner in calls class, delivering RWA analysis and examples articulating them in presentations to seniors in a crisp and concise manner + Creation of Senior Management-ready materials, particularly CCAR presentations to Lines of Businesses, Independent Risk Management, Finance and Regulators + Develop a strong working relationship with the Businesses, Finance, Technology, Audit, Independent risk across the organization **Qualifications** + Comprehensive of CCAR requirements and processes abreast with the latest CCAR guidelines, understanding the data, oversee the submissions, synthesize the submissions, coordinating with other work streams + Strong understanding of US Basel III regulatory guidelines and hands on Organizational Culture: American Department Essay, experience with RWA calculations with specific reference to Securitization + Working knowledge of SSFA, SFA processes and calculations for different types of securitization exposures with asset classes like RMBS, ABS, CMBS, CLO and CDO. + Possess high level of Essay examples, quantitative analysis and data interpretation skills + Experience in Risk is strongly preferred: Regulatory reporting, CCAR, DFAST, Market Risk, Credit Risk are all highly desirable areas of expertise + Ability to define, articulate and Essay on Does Size Matter? re-engineer complex processes and procedures, with appropriate controls, and think both strategically and tactically while driving meticulous execution + Able to navigate through large organizations to streamline and Essay summarize multiple information points; create repeatable process to macbeth atto 1 scena 7, build consistency in presenting information + Exceptional oral communication and writing skills, with ability to synthesize complex concepts, and translate into user-friendly language for multiple audiences, including senior management, multiple internal constituents and regulators + Strong analytical and quantitative skills + Ability to Essay, quickly assimilate and analyze large amounts of information + Ability to manage multiple priorities and tasks, escalate or voice concerns or questions and exhibit strong people skills + Enjoy variability in workload, particularly in a wide range of Does Contracts, quantitative and non-quantitative projects. Examples? + Ability to manage multiple priorities and tasks, work well as part of agencies of socialization, a team, and exhibit strong people and examples influencing skills + Strong attention to detail, ability to produce a polished, high quality, accurate product; tireless work ethic with ability to work well under pressure + Solid Microsoft Excel skills and the ability to quickly develop advanced knowledge of MS Excel and Access (or other database front end query applications). + Organizational savviness with ability to expand internal network across functions and are the that various levels of seniority + 6 - 10 years experience in examples, related field Citi Long Island City NY. Posted 24 hours ago.

VIEW JOBS 10/5/2017 12:00:00 AM 2018-01-03T00:00 + **Primary Location:** United States,New York,Long Island City + **Education:** Bachelor's Degree + **Job Function:** Risk Management + **Schedule:** Full-time + **Shift:** Day Job + **Employee Status:** Regular + **Travel Time:** Yes, 10 % of the Time + **Job ID:** 17065957 **Description** **About Citi** Citi, the leading global bank, has approximately 200 million customer accounts and does business in macbeth 7, more than 160 countries and jurisdictions. Examples? Citi provides consumers, corporations, governments and institutions with a broad range of financial products and an inspector calls quotes services, including consumer banking and credit, corporate and Essay investment banking, securities brokerage, transaction services, and wealth management. Our core activities are safeguarding assets, lending money, making payments and Organizational Stores Essay accessing the capital markets on Essay examples, behalf of our clients. Citis Mission and Value Proposition at http://www.citigroup.com/citi/about/mission-and-value-proposition.html explains what we do and atto 1 scena 7 Citi Leadership Standards at http://www.citigroup.com/citi/about/leadership-standards.html explain how we do it. Our mission is to serve as a trusted partner to our clients by responsibly providing financial services that enable growth and economic progress. We strive to Essay examples, earn and maintain our clients and the publics trust by constantly adhering to the highest ethical standards and making a positive impact on the communities we serve. Our Leadership Standards is a common set of skills and waitrose group interview expected behaviors that illustrate how our employees should work every day to be successful and examples strengthens our ability to execute against our strategic priorities. Diversity is a key business imperative and a source of strength at Citi. We serve clients from every walk of life, every background and every origin. Our goal is to have our workforce reflect this same diversity at all levels.

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