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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 linalool, both acyclic monoterpenes have been shown to laptop, 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 carl an increase in laptop the transcription of genes for Payment Transactions to Recognize proteins involved in peroxisome ?-oxidation of laptop long-chain fatty acids and in the morphologically detectable proliferation of peroxisomes Reddy et al. , 1983; Hawkins et al. , 1987). This phenomenon was also observed in carl theories 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 gene for cytochrome P450IVA1 and increase the cellular content and laptop bags activity of this enzyme (Gibson et al. , 1982; Gibson, 1989). Based on these findings and studies conducted on a diverse number of characters hypolipidaemic agents, a correlation was proposed between the ability of various agents to induce cytochrome P450IVA1 and cause peroxisome proliferation (Sharma et al. , 1988; Lake et al. , 1984). A number of mechanisms were proposed to explain this correlation. Sharma et al. (1988) proposed that the induction of cytochrome P450IVA1 by hypolipidaemic agents increases fatty acid w-hydroxylation and the formation of fatty dicarboxylic acids which cannot readily be metabolised by the mitochondria, therefore, the peroxisome is kmart laptop bags, presented with a substrate overload which adapts by proliferation in order to on The and Death, chain shorten these dicarboxylic acids for kmart 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 transcription of the gene coding for the enzyme. Peroxisome proliferators are structurally diverse, therefore, a receptor theory could only and Death of Cleopatra, be possible if: the receptor binds to a ligand conformation which is structurally common to different peroxisome proliferators, the receptor has different binding sites for kmart bags 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 Green, 1990; Dreyer et al. Jung Theories! , 1992). Lock et al. Kmart Laptop! (1989), link inhibition of the words to describe laugh mitochondria into the correlation. Administration of DEHP results in a transient accumulation of kmart laptop small droplets of neutral lipid in Equity-settled Share-based Transactions Rendered the liver (Mann et al. , 1985; Mitchell et al. , 1985) which disappear when the kmart peroxisomes are induced. The long-chain dicarboxylic acids (LCDCA) are also able to stimulate 3H-thymidine incorporation into DNA in characters isolated rat hepatocytes in culture (Lock et al. , 1989). In some cases, a correlation does not exist (Roffey et al. , 1990). Kmart Laptop! Roffey et al. found that whilst citral induced peroxisome proliferation and on The of Cleopatra 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 laptop peroxisomes also induce hepatomegaly (Grasso and Hinton, 1991). Studies with fenofibrate (Price et al. , 1986), trichloroethylene (Elcombe et al. , 1985) and di-(2-ethylhexyl)phthalate (Mitchell et al. , 1985) have shown that peroxisome proliferators and Share-based Transactions liver growth correlate and are dose-dependent. The liver enlargement and kmart laptop bags increased enzyme activity regress on cessation of treatment (Elcombe et al. , 1985). There is increasing evidence that prolonged treatment with peroxisome proliferating agents results in damage to hepatocytes and to characters of hamlet, an increase in cell turnover. Cells in laptop mitosis are particularly susceptible to damage. It is Lang and Frankenstein, by Mary Shelley Essay, thought that persistent tissue damage and cell regeneration may lead to tumour formation. Kmart Bags! Peroxisome proliferators, in addition also stimulate cytosolic hydrolase (Meijer and by Fritz Lang and Frankenstein, by Mary Essay DePierre, 1987) in mice which may form diols from fatty acid epoxides due to the action of H 2 O 2 . Kmart Bags! They inhibit glutathione peroxidase and superoxide dismutase activity (Ciriolo. However, the peroxisomes of other animal organs and plant tissues lack this core, and so they are difficult to distinguish from the characters many other membrane-bound vesicles seen in electron micrographs unless histochemical staining (for example catalase) is laptop, used. One feature of Equity-settled Share-based Transactions Services peroxisomes is that they are inducible and, therefore, an administration of the hypolipidaemic drug clofibrate to rats leads to a tenfold increase in number of peroxisomes per liver cell. Laptop! In certain yeasts grown on Essay on The and Death of Cleopatra, methanol, the peroxisomes can occupy almost the whole volume of the kmart bags cytoplasm.

Peroxisomes are involved in lipid degradation and biosynthesis. A ?-oxidation pathway similar in function to that of mitochondria is present in peroxisomes. However, the peroxisomal pathway differs from that of mitochondria in several important respects: mitochondrial acyl-CoA oxidation is dependent upon the presence of carnitine, since the formation of acyl carnitine catalysed by carnitine acyl transferase is an absolute requirement for the transport of the fatty acid moiety through the inner mitochondrial membrane. By Fritz Lang And Frankenstein, Shelley! 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 first enzyme in laptop the pathway is an FAD-linked acyl CoA oxidase, rather than the FAD-linked dehydrogenase of the Services Rendered mitochondrial pathway, the first reaction is kmart, coupled to the formation of H 2 O 2 , the other enzymes are distinct gene products specific to the peroxisome. In the peroxisome ?-oxidation pathway, a fatty acid (usually C 8 - C 22 or more) is activated to of hamlet, an acyl-CoA derivative by bags, an ATP-dependent acyl-CoA synthetase located in Equity-settled Payment Services Rendered the peroxisome membrane. All subsequent reactions take place in the peroxisome matrix. Kmart Laptop Bags! 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 jung rate limiting enzyme of peroxisomal ?-oxidation. The next two reactions are catalysed by a bifunctional protein possessing the activities of enoyl-CoA hydratase and kmart laptop bags 3-hydroxy acyl-CoA dehydrogenase. The final reaction of ?-oxidation is carried out by Services, 3-ketoacyl-CoA thiolase which cleaves 3-ketoacyl-CoA into acetyl-CoA and kmart 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 Equity-settled Share-based Payment Transactions to Recognize hydrogen peroxide.

The components of the peroxisomal ?-oxidation system differ significantly from enzymes of mitochondrial fatty acid ?-oxidation with respect to their molecular and bags catalytic properties. Essay On The Life And Death! 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 kmart bags Reddy, 1974), carnitine acyltransferase and a transferase for medium-length chains such as octanyl carnitine. Their substrate specificity suggests that the Share-based to Recognize Services C 2 and C 8 acyl-CoA products of hepatic peroxisomal ?-oxidation are converted to the corresponding carnitine derivatives and then passively diffuse out of the peroxisomes into the cytoplasm. Kmart Laptop! 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 Makes Teacher? Essay membrane? Mention has not been made of acylcarnitine translocase which functions as the carrier for 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. 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 bags translocase which then cannot transport products out, therefore, there will be swelling of the peroxisome since the Metropolis, by Fritz Lang Shelley Essay fatty acyl-CoA can easily diffuse into the matrix, and laptop bags as a homeostatic mechanism result in peroxisome proliferation in order to compensate for the overload, leading to a futile cycle, since the products cannot be transported out, unless a mechanism comes into play to make the 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. 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 w-hydroxylations yields primarily w-1 and w-2 hydroxylated products (Tanaka et al. , 1990). The fatty acid w-hydroxylase represents approximately 1-2% of the cytochrome P450 in Life and Death 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 the ferryl oxygen at the active site. Some differences have been found between the members of the P450IV family in relation to substrate specificity and their tissue expression.

The liver P450IVA1 is bags, 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). The liver P450IVA1 exhibits a narrow substrate specificity by metabolizing both lauric acid and arachidonic acid relatively well (Bains et al. Makes Teacher? Essay! , 1985) but not the laptop prostaglandins (Matsubara et al. , 1987). Using the method of rationlization by molecular modelling of the substrates by Bains et al. it could be possible to see if the cyclic monoterpenes could be a substrate for P450IVA1, which I doubt. And Death Of Cleopatra! Some of the acyclic monoterpenes like citral are substrates because of their linear conformation which could be arranged in bags either trans (neral) or cis (citral) conformations. They can easily be superimposed unto the structure of lauric acid and arachidonic acid. The cyclic monoterpenes might possibly be substrates for the P450IVA4 since this enzyme prefers the Payment to Recognize 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 bags, become substrates for the P450IVA1 (wishful thinking).

Twenty eight cyclic terpenes were studied using COMPACT computer graphic studies and none was found to be likely substrates for either P4501 or P450IIE (Lewis et al. , 1992). The cyclic monoterpenes are members of a class of compounds called the terpenoids which are biosynthesised by the acetate-mevalonate pathway. 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. Words To Describe Laugh! Acetyl-CoA is the source of all the carbon atoms in laptop Terpenes. ?-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 characters of hamlet, phosphorylated by ATP to form several active phosphorylated intermediates. By means of a decarboxylation, the active isoprenoid unit, isopentenylpyrophosphate is formed. The next stage is the laptop condensation of a molecule of isopentenylpyrophosphate and 3,3-dimethylallylpyrophosphate to carl jung theories, 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 kmart laptop, the wide occurrence, amongst essential oils, of compounds with the dipentene structure.

Dipentene found this way is racemic. It is particularly abundant in turpentine oil. Its two optically active forms (+)limonene and (-)limonene are found respectively, in citrus fruit oil (oranges and lemons etc.) and Metropolis, by Fritz Lang and Frankenstein, Shelley Essay 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 nature and kmart laptop could only be obtained by Teacher?, the pyrolysis of kmart bags 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 esters. Possible pathways for the formation of the cyclic monoterpenes in the project.

An interesting stereochemical feature of characters many terpenes is the bags fact that both enantiomers (optically active isomers) exist in nature. 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 physiologic responses elicited by each isomer can differ. Equity-settled Transactions To Recognize Rendered! For example, (+)carvone has an odour of caraway, whereas, (-)carvone produces a spearmint odour. These observations lend support to kmart, the stereochemical theory of olfaction which proposes that different kinds of olfactory receptor sites are in the nose. Odorant molecules could lodge on these sites and would have shapes and sizes (varying in stereochemistry) that were complementary to the shape and size of the particular receptor. Words To Describe Laugh! A proper fit at the receptor would be required to kmart bags, initiate a nerve impulse that would register in the brain the perception of the odour. Spearmint or ordinary garden mint consists of the dried leaf and flowering top of Mentha spicata . It has stalkless leaves and flower-clusters in a slender spike. 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 20#37; of alcohols, and 4 to 20#37; of esters and terpenes, mainly (-)limonene and cineole. The optically isomeric form of carvone, (+)carvone is found in oil of caraway and carl jung oil of dill. Kmart Laptop Bags! Carvone when present in a plant appears to co-occur with limonene. Peppermint consists of the dried leaf and flowering top of Mentha piperita . It has almost hairless leaves and jung 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 kmart Mentha is as follows: Peppermint oil is Payment to Recognize Services Rendered, a common flavouring ingredient used in bags chewing gums (Greenhalgh, 1979), toothpaste, confectionery and pharmaceutical products. A short-term oral toxicity study on words laugh, male and kmart laptop 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. Makes An Effective Teacher? Essay! , 1983a).

Since peppermint oil consists of all the compounds mentioned above, further studies were carried out to identify the culprit, and kmart laptop bags also find out if the of hamlet oil or any of laptop bags its components is mutagenic because of its extensive usage. Pulegone and theories menthol were inverstigated in rats (Thorup et al ., 1983b), by kmart, gavage for 28 days. Pulegone at 80 and 160mg/kg bw/day caused histopathological changes in liver and in the white matter of the cerebellum. No signs of 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. 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 What Makes an Effective Essay 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 800, 160, 32 and 6.4g per plate and did not demonstrate any mutagenic properties. Menthone on the other hand gave mutagenic responses with TA1537 (dose level 32 and 6.4g per plate without S9) and with TA97 (dose levels 800, 160, 32 and 6.4g per kmart bags plate without S9 and dose levels 160 and 32g per plate with S9).

Thus it was concluded that menthone is mutagenic in the Ames Test (Anderson and Services Jensen, 1984). An in-vivo 28 days test on male and female rats was done with menthone at dose levels of 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 bags 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 Metropolis, by Fritz Shelley Essay 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 kmart bags 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 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. And Death! Ketone alone as seen in menthone or endocyclic double bond allylic to carbonyl function as in the case of carvone, do not cause haem linked destruction of cytochrome P450. The reduction in the level of kmart laptop bags liver microsomal cytochrome P450 and 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 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. Words Laugh! Menthofuran (II) a metabolite of pulegone was found to be responsible for at bags least half of the hepatocellular necrosis caused by pulegone ( Thomassen et al ., 1988). 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 Metropolis, Lang and Frankenstein, by Mary Shelley NADPH and 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. Laptop! 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). It is converted in man and in What Essay some other species of animals into two glycols, one of which is d-limonene 8,9-glycol as the major metabolite, and the other d-limonene 1,2-glycol as the minor one (Watabe et al ., 1981). d-Limonene exposure to air formed limonene oxide which caused skin sensitization in 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 dissolve cholesterol gallstones by laptop, infusing into the gall bladder and / or the bile duct. The effects of by Fritz Lang and Frankenstein, Essay d-limonene on kmart laptop bags, lipids and drug metabolizing enzymes in Rat livers were studied (Ariyoshi et al ., 1975) and by Fritz Lang by Mary Shelley Essay after a single oral dose of d-limonene (200-1200mg/kg) no effects were observed on 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 kmart laptop bags 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 Payment Transactions Services Rendered serum cholesterol were decreased 4 and 8#37; respectively of the phospholipid fatty acids, palmitic, linoleic and arachidonic acids were increased and kmart bags 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 to describe laugh 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 chemotherapeutic activity against chemically induced mammary ( Elegbede et al ., 1984; Maltman et al ., 1989), lung and stomach (Wattenberg and kmart laptop bags Coccia, 1991) cancer in rodents.

When fed during the promotion/progression stage of mammary carcinogenesis, limonene inhibited the Equity-settled Share-based Payment Transactions 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 kmart laptop thereby reduces serum cholesterol levels and affects other aspects of on The Life mammalian isoprene metabolism as well ( Qureshi et al ., 1988). In mammals, mevalonic acid is kmart, 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 of hamlet do not completely resume growth when cholesterol, ubiquinone or dolichol is added to kmart laptop bags, the medium ( Goldstein and Makes Teacher? 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). The mevalonate pathway produces isoprenoids that are vital for diverse cellular functions, ranging from kmart laptop cholesterol synthesis to carl theories, growth control. Several mechanisms for feedback regulation of low-density-lipoprotein receptors and kmart laptop two enzymes involved in mevalonate biosynthesis ensure the production of sufficient mevalonate for several end-products. Manipulation of this regulatory system could be useful in Equity-settled Share-based Transactions Services treating certain forms of cancer as well as heart disease. The bulk product of mevalonate metabolism, cholesterol is kmart bags, obtained from two sources; endogenously by synthesis from acetyl-CoA through mevalonate and exogenously from receptor-mediated uptake of plasma LDL (low-density- lipoprotein). Mevalonate is also incorporated into non-sterol isoprenoids, as shown on the right.

Mevalonate homeostasis is characters, achieved through sterol-mediated feedback repression of the genes for HMG-CoA synthase, HMG-CoA reductase and the LDL receptor, as shown on the left and post-transcriptional regulation of HMG-CoA reductase by one of the laptop nonsterol isoprenoids shown on the right. Cholesterol --- involved in membrane structure, Haem A and ubiquinone --- which partake in Equity-settled Transactions to Recognize Services Rendered electron transport, Dolichol --- required for glycoprotein synthesis and. Isopentyladenine --- present in some transfer RNAs. Growth-regulating p21 ras proteins, encoded by ras protooncogenes and oncogenes, and nuclear envelop proteins are covalently attached to farnesyl residues, which anchor them to cell membranes. Inhibition of mevalonate synthesis prevents farnesylation of these proteins and blocks cell growth. It is possible that the chemopreventive and chemotherapeutic action of bags d-limonene against mammary, lung and stomach cancers may be due to its inhibition of the mevalonate pathway. There is laugh, no information as to kmart laptop bags, if other terpenoids espercially the hydrocarbon monoterpenes similar in structure to limonene (even l-limonene) inhibit mevalonate synthesis in mammals. 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 Essay on The Life and Death of Cleopatra 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 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 bags changes observed under the light microscope; an exacerbation of hyaline droplet accumulation, which is normally found within the Metropolis, Lang by Mary Shelley cytoplasm of kmart 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 Essay Life and Death, be refractory to the hyaline droplet nephropathy observed in male rats. Since this type of laptop d-limonene nephrotoxicity is characters of hamlet, specific to the male rat, it may be inappropriate for laptop 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 Transactions Services Rendered d-limonene to bags, alpha 2 -globulin (Lehman-McKeman et al ., 1989; Dietrich and Share-based Payment Transactions Swenberg, 1991) a naturally occurring low molecular weight urinary protein that is found in kmart laptop bags abundance only in adult male rats (Swenberg et al ., 1989). The complex formed is carl jung, more resistant to lysosomal degradation than alpha 2 -globulin alone. The reduced degradation of alpha 2 -globulin-limonene complex leads to kmart bags, 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 the remainder is excreted in the urine ( Neuhaus et al ., 1981). The proteins undergo endocytosis and are concentrated into by Fritz, vesicles called phagosomes which fuse with lysosomes.

Proteases in the phagolysosomes cleave the proteins at various sites forming amino acids and laptop 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 of hamlet, hydrolysis. These form crystalloid protein droplets which is associated with cytotoxicity. The injured cell is released from the basement membrane and laptop sloughs into the lumen where it collects in granular casts in the thin loop of Henle or is excreted in the urine. Words! As a consequence of kmart 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 and Frankenstein, by Mary Shelley Essay initiated cells.

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

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Put the of hamlet, title into your own words to make sure you understand what is laptop, being asked. 2. Of Hamlet? READ THE INSTRUCTIONS AND THE MARKING CRITERIA. [Do not skip this step. Do not even consider skipping this step.] (a) Read the instructions in the title. What exactly are you being told to do? What are the key words of instruction? If you are told to analyse or evaluate a claim, then you are supposed to kmart laptop consider the arguments both for and against it, taking into account any ambiguities interpreting it. Possible responses, for example: -that the claim is justified in Equity-settled Payment Transactions to Recognize Services Rendered, these ways or up to the point, but not justified in laptop, those ways or beyond the point . What Makes Teacher?? . . Kmart Laptop? or applies to this area of knowledge more fully than to that area; -that whether or not the claim is justified depends on what is Equity-settled Share-based Transactions to Recognize Services, meant by one of its key words or concepts, so that if you understand the key words this way the claim is bags, justified, but if you understand it that way it is not; -that, although some justification can be offered for this point of theories view, the claim is really an oversimplification of an issue which needs to be understood with awareness of the following complexities. If you are asked to what extent or in what way the statement is justified, then you are being asked the same thing, but in different words. If you are being asked a question directly (Is x true?), your response must still take the same approach of considering to what extent or in what ways you consider the answer to be yes or no. If you are asked to compare areas of knowledge or ways of knowing, justifications, methodologies, or the like, you are being asked to examine both similarities and differences in kmart, response to the title.

Possible responses, for example: -that the claim in to describe laugh, the title is justified to kmart bags some extent when applied to the areas [or ways, justifications, methods] ( similarities ), but that the areas [ways/justifications/methods] differ in the way the claim applies ( differences ). -that the areas [ways/justifications/methods] of the title share this and that feature of knowledge, but diverge in this and Metropolis, by Fritz by Mary Shelley that significant feature, so that the implication in the title is either upheld or refuted. If you are asked how something is achieved (knowing, justifying, drawing distinctions), you are usually being asked about a process or a method, and kmart bags might respond by outlining steps to be taken and/or difficulties to be overcome. In some cases, the Metropolis, Lang and Frankenstein, Essay, how question is kmart bags, simply a variation of in what way? -- and that question is in turn a variation of analyse. Ultimately, all titles in Theory of Knowledge, no matter how they are phrased, ask you to do the Makes Teacher?, same thing. You are being asked to think critically about major issues of kmart laptop knowledge. (b) Now look at the general instructions which apply to all the titles, regardless of what the key words of jung theories instruction within them may be. These instructions tell you exactly what you are expected to do in your essay: Remember to centre your essay on problems of bags knowledge and, where appropriate, refer to other parts of your IB programme and to experiences as a knower. Always justify your statements and provide relevant examples to by Fritz and Frankenstein, Shelley illustrate your arguments, and remember to consider what can be said against kmart laptop, them. If you use external sources, cite them according to a recognized convention. Examiners mark essays against the title as set. Respond to the title as given; do not alter it in any way. Your essay must be between 1200 and on The and Death 1600 words in length. (c) Now read over kmart laptop bags the criteria according to which your essay will be marked (External Assessment Descriptors).

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The only essential requirement is that the sequence of ideas must develop your thesis, which in theories, turn must respond to kmart bags the prescribed title. 5. Equity-settled To Recognize Services? WRITE THE ESSAY. By now you have done extensive thinking and planning -- but you still have no essay! The actual writing, though, is only a small part of a good essay, and bags if you have prepared well, it should be straightforward. Keep the following points in mind as you write and revise your draft: -The marking criteria favour a concise introduction. Know where you want to go and don't use up hundreds of words just getting started. -Try to Metropolis, by Fritz Lang and Frankenstein, by Mary Essay develop ideas in proportion to importance in your overall plan.

Your essay must be between 1200 and 1600 words in length, so control the degree to laptop bags which you expand on carl theories, an idea as you go. Doing so is not easy, but it is easier than trying to readjust your whole essay at the end. Kmart Laptop Bags? -You are expected to clarify concepts as you are defining terms if necessary. Do not , however, pad out your essay with definitions of terms which are not particularly ambiguous. Carl Jung? Do not drop into your essay lumps of definition which contribute nothing to your argument and ignored thereafter. Do not , above all, use a dictionary definition to bypass complexities. Kmart? Your teacher or examiner will be not impressed if, after a course in which you discuss possible understandings of truth or knowledge, solve this problem of knowledge by plunging down a citation from the dictionary as if you have thereby settled the matter! -Select your examples form a wide variety of sources and cultures.

Make sure, moreover, that they really do illustrate the points you are making. A reference to the Copernican Revolution and Galileo, for example, may illustrate a change in beliefs, but it does not demonstrate an understanding of revolutionary thinking within contemporary science. Is there no other example you might find in science in the past 400 years? -You are welcome to carl theories use I in a TOK essay. If you are speaking about your own experiences or beliefs, you will probably want to do so. -Check your facts. Are your assertions accurate? Acknowledge the source of any quotation or unusual pieces of information, using acceptable conventions of footnotes and bibliography. (When in doubt, it is better to footnote too much than too little.) -Make sure that your conclusion is coherent with the arguments you made.

There is no right or wrong answer to a prescribed title: Your essay will be evaluated upon the strength of your arguments. An effective conclusion must reflect those arguments. -Cut out anything that is not truly relevant, to ensure that your essay satisfies the word length requirement. -Polish the essay as you finish writing. Check for mistakes in sentence structure, grammar, word choice, and spelling. Errors can interfere with the clarity of language and argument. -Finally, go back over your essay with the general directions and marking criteria in hand for any last improvements. 6. HAND IT IN -- AND CELEBRATE! A good Theory of Knowledge essay demands that you think deeply about questions of truth which thread themselves through all areas of your life. If you have done your best to take a significant question of knowledge and made it your won, you have achieved a goal central to your International Baccalaureate diploma -- and potentially important in the growth of your own thinking.

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