Equitable doctrine of promissory estoppel

Introduction Under the equitable doctrine of promissory estoppels, promises that are made in bad faith in an agreement can be prosecuted in the court of law. Specifically, promissory estoppel allows other parties in the agreement to seek justice when the initial promises made were done in bad faith. Thus, this reflective treatise attempts to explicitly explain how the equitable doctrine of promissory estoppel is unjustifiable.Advertising We will write a custom essay sample on Equitable doctrine of promissory estoppel specifically for you for only $16.05 $11/page Learn More Why the equitable doctrine of Promissory Estoppel is Unjustifiable In the famous ruling in the case Waltons Stores (interstate) Ltd v Maher, the verdict gave the applicant a relief based on the defendant’s promise in the business contract. Reflectively, â€Å"the essence of the principle is that it requires a defendant to make fair and just compensation derived at the expense o f a claimant† (Doctrine of Promissory Estoppel 2012). This is brought out in the case of Pavey Mathews Pty Ltd v Paul. The principle can form the basis for which a claimant can seek relief. However, action based upon unjust enrichment is not based on the contract but independent of it (Turner 2005). As opined by Turner (2005), â€Å"restrictive covenants may, if certain conditions are satisfied, run with the land and bind purchasers of it to observe the covenants for the benefits of adjoining owners† (Tuner 2005, p. 43). An example is the Tulk v Moxhay 1848. In this particular case, the claimant had a listing of several real estate properties in Leicester square which he sold to the defendant based on an unwritten promise of safety standard guarantee. The defendant Elms pledged as a good will to the claimant, he would ensure that the railings and the gardens of the said properties would be maintained in their present condition and he will allow individuals tenants to t ill the gardens. The fact of the agreement was that the defendant had a prior knowledge of restrictions stipulated in the agreement with the claimant. Unfortunately, the defendant did not honor the said agreement made in form of a promise. The â€Å"defendant announced that he was going to build on the land, and the claimant; who still owned several adjacent houses, sought an injunction to restrain him from doing so from the court. It was held that the covenant would be enforced in equity against all subsequent purchasers with notice† (Doctrine of Promissory Estoppel 2012, par. 15). State laws expressly grant exceptions. This is though the various acts. For example, the Insurance Contract Act 1985, Bills of Exchange Act 1909, Cheques Act 1986, and Motor vehicle (Third party Insurance) Act 1942. For instance, â€Å"under the law of insurance, the exception to the principle of equitable doctrine of promissory estoppel has been applied to insurance policies are effected for the benefit of an upset party.Advertising Looking for essay on common law? Let's see if we can help you! Get your first paper with 15% OFF Learn More Where a policy of insurance is affected by the assured for his own life, and the policy is expressed to be for the benefit of his wife† (Doctrine of Promissory Estoppel 2012, par. 15). However, she cannot sue the insurance company on the policy unless it is assigned in writing or a trust has been declared by assured (Stone 2008). Therefore, a stranger to the contact cannot sue even if the contract is avowedly made for his benefit. Thus, â€Å"a stranger to the consideration cannot enforce an action on the promise made between two persons unless has in some way intervened in the agreement† (Doctrine of Promissory Estoppel 2012, par. 17). In the case, the person making the claims was due to get married to G’s daughter. The two parties allegedly made a written agreement in form of a promise note. The parties to the contract agreed to pay the claimant some money. Upon failing to honor the agreement, G was sued by the claimant. Though the sole object of the contract was to secure benefit to the claimant, he was not allowed to sue (Doctrine of Promissory Estoppel 2012). This is because the contract existed with the father and not with him. Besides, businesses often get into informal agreements with other businesses. The aim of these agreements is to facilitate smooth flow of work. Transactions resulting from such agreements need to be recorded in the books accounts in accordance with the accounting principle despite being informal. Therefore, an extension of liability ruling will frustrate informal agreements that determine success of the formal business contracts (Keenan Riches 2002). Aiders and abettors are parties to an offense. They share crime intent with the person who commits the crime. They may be liable as a principal, an accessory before or after the fact. Aiders and accomplice s are liable for fraudulent misrepresentation when they execute some overt act, or give advice or encouragement to commit a crime. The claimant bears the burden of proof. He must prove that there is a material misstatement or deceptive conduct, wrongful state of mind, a connection with the purchase or sale of a security, reliance, economic loss, and loss causation. Unfortunately, the equitable doctrine of promissory estoppels is silent on the fate aiders and abettors in a contract. This implies that when a trader has material information that is not known to the other party and he carries out trade with it, then the gains from the trade are unfair prima facie. However, there is no blanket court rule that declares trading with material insider information as illegal. The court handles cases arising from unfair trade in isolation. Therefore, it emerges that trading with material nonpublic information is unethical but may not be essentially against the law (August 2008).Advertising We will write a custom essay sample on Equitable doctrine of promissory estoppel specifically for you for only $16.05 $11/page Learn More From the above reflection, it is apparent that the equitable doctrine of promissory estoppels may not be justifiable in the face of ethics in business contracts. References August, R. (2008). International Business Law: Text Cases and Readings. New York: Routledge. Keenan, D, Riches, S. (2002). Business Law. New York: Pearson/Longman. Doctrine of Promissory Estoppel. (2012). Web. Stone, R. (2008). The Modern Law of Contract. New York: Routledge. Turner, C. (2005). The Comprehensive Guide to all the facts Contract Law. Hodder: Oxon. This essay on Equitable doctrine of promissory estoppel was written and submitted by user Carolina Mullins to help you with your own studies. You are free to use it for research and reference purposes in order to write your own paper; however, you must cite it accordingly. You can donate your paper here.

Free Essays on Automobile Pollution

I. Introduction In the past century, the automobile has come a far way from Henry Ford’s Model T. In the United States there has always been a high demand for cars, and with that demand comes the need for speed, and a need to have the best. And that is what major automobile industries have been giving our society because they know that they can profit greatly from it. These industries know what sells and they take advantage of it. In order to improve automobiles so that they meet these needs of our society, automobile industries turn to technology. Technology is what has turned the Ford Model T into a Ford Mustang 5.0. Of course with this technology comes flaws. The biggest and most obvious flaw is pollution. Because of pollution, we find ourselves asking the question of whether this technology has helped our society more than it has hurt it. And now that we have identified the problem, how can it be fixed, and how will fixing the problem of automobile pollution affect society also? II. Economic/Social Issue Pollution is becoming a big problem in today’s world. We are wrecking the earth day by day and automobiles are a very big part of that. As SUV’s get more and more popular, the pollution just increases. This world has become a very selfish place and people think only about themselves. They don't care that we are ruining the earth and soon enough, this world will not be livable. But as long as the earth is fine for right now, no one really cares. We like to put the blame on the business’ saying that it is their fault, but they make what we will buy. As long as the demand for SUV’s are so high, none of these car companies are gonna put much interest into the hybrid vehicles. It is up to the consumers to embrace this environmentally friendly way of living. Once the consumers allow change to take place, and put the value of life over their own possessions, we will be able to make the certain steps in cleaning ... Free Essays on Automobile Pollution Free Essays on Automobile Pollution I. Introduction In the past century, the automobile has come a far way from Henry Ford’s Model T. In the United States there has always been a high demand for cars, and with that demand comes the need for speed, and a need to have the best. And that is what major automobile industries have been giving our society because they know that they can profit greatly from it. These industries know what sells and they take advantage of it. In order to improve automobiles so that they meet these needs of our society, automobile industries turn to technology. Technology is what has turned the Ford Model T into a Ford Mustang 5.0. Of course with this technology comes flaws. The biggest and most obvious flaw is pollution. Because of pollution, we find ourselves asking the question of whether this technology has helped our society more than it has hurt it. And now that we have identified the problem, how can it be fixed, and how will fixing the problem of automobile pollution affect society also? II. Economic/Social Issue Pollution is becoming a big problem in today’s world. We are wrecking the earth day by day and automobiles are a very big part of that. As SUV’s get more and more popular, the pollution just increases. This world has become a very selfish place and people think only about themselves. They don't care that we are ruining the earth and soon enough, this world will not be livable. But as long as the earth is fine for right now, no one really cares. We like to put the blame on the business’ saying that it is their fault, but they make what we will buy. As long as the demand for SUV’s are so high, none of these car companies are gonna put much interest into the hybrid vehicles. It is up to the consumers to embrace this environmentally friendly way of living. Once the consumers allow change to take place, and put the value of life over their own possessions, we will be able to make the certain steps in cleaning ...

American Airlines Flight 1420 Research Paper Example | Topics and Well Written Essays - 1000 words

American Airlines Flight 1420 - Research Paper Example , underscore several key human factor failures and investigate how each of them generated some other failures by that creating a chain of errors that finally materialized to the accident. We shall address safety recommendations that would prove useful in the air travel industry. The findings regarding the accident of the McDonnell Douglas DC-9-82 (MD-82), N215AA reveal a situation that featured 2 flight crew members. It involved four flight attendants and 139 passengers (Aircraft accident report, 2001). The death toll hit 11, a tally that featured the captain and ten passengers. There were serious and minor injuries featuring 105 passengers, the first officer, and flight attendants. 24 passengers sustained no injuries (Aircraft accident report, 2001). The plane suffered destruction from impact forces plus post-crash fire (Aircraft accident report, 2001). Details regarding the crew operating American Airlines flight 1420 affirm that the captain and first officer were certified and qualified under the federal and company requirements. They were medically fit to conduct the flight with no tangible evidence of pre-existing conditions that would have adversely altered their performance. They were placed in charge of an equipped, certified and well-maintained aircraft with no evidence to suggest pre-existing failures of the engine and the entire system (Aircraft accident report, 2001). All decisions and outcomes were thus dependent on the flight crew soon after the departure. The accident was prompted partly by human mishap.The findings suggest that the initial decision to descend into the terminal area was marred by an approaching thunderstorm. However, the crew were rational enough to imagine that they would reach that particular area before the thunderstorm (Aircraft accident report, 2001). The weather factor poses a potential threat to the safety of the entire flight. But decisions regarding a last minute change of course of action would only happen when there is

Effective Business Planning Case Study Example | Topics and Well Written Essays - 1250 words - 2

Effective Business Planning - Case Study Example The organization has engaged effective organizational strategies by differentiating, developing effective marketing plans and penetrating the market through effective management of both people and resources. Mattel is a global toy manufacturing company that has numerous branches across the world. The company initially started with the goal of becoming a global leader in the toy manufacturing industry and to remain in this position indefinitely. However, the market environment is composed of many unpredictable limiting forces that act as barriers to market entrants and expose the organization to severe business forces that threaten survival in this market (Dressler, 2004). Mattel’s experience environmental threats, competition, ethical challenges and market fluctuations that became big threats to its survival in the market. The ability of the organization to maintain its current position today can be attributed to its ability to overcome its challenges and take advantage of the opportunities in the market while still remaining innovative in a world of changing technology. Mattel was founded back in 1945 when its main product was picture frames on a retail basis. The company later turned to the toy industries after recognizing this as a better market with higher profits and more customers. In 1960, the company became a publicly owned company and its sales remained high making it maintains its position as the world’s largest toy company. The company now has its roots in design, manufacture, and marketing of family products. The company owns more than 8 company brands and has differentiated to over 36 countries and now markets its products to over 150 nations. One of the strategies that Mattel has employed in surviving in the competitive market is the use resource and people management strategies. The company has remained strong in acquiring the right employees and leaders within the organization.

Exercise metabolism Research Paper Example | Topics and Well Written Essays - 1000 words

Exercise metabolism - Research Paper Example These studies give an insight on how nutrition affects exercise performance and metabolism. They have different results and findings. However, all of them are geared towards understanding the connection between nutrition and exercise. Nutrients included in these studies include both artificial and natural nutrients. The paper also ensures gender balance because exercise metabolism and performance is different between men and women. Hence, it looks at findings of research done on women. Human beings have different capabilities to exercise. The capability of a human being to exercise is dependent on the biological ability of his or her body to change chemical energy in the skeletal muscle to mechanical energy. Adenosine triphosphate is the chief chemical energy source in skeletal muscles. During exercise, it is characteristic of ATP storage to be depleted fast if it is not quickly replenished. This is mainly caused by the increased demand for ATP resulting from exercise. In many scenarios, when exercising, ATP need and availability are exactly balanced. AT storage is also upheld. Hence, ATP providers in contracting skeletal muscles which are known as metabolic pathways quickly react to the high demand for ATP. What determines ATP demand? ATP demand is determined by the contraction rate of skeletal muscles and the power yield during exercise. Metabolic pathways are described by the enzymes that digest ATP in an exercise session. These enzymes include ATPase, potassiu m transport, and calcium transport ATPase, and actomyosin ATPase. These enzymes are related to the contraction – relaxation cycle (Hargreaves & Lawarence, 1). Homeostasis is key for the proper functioning of the human body, be it during exercise or at rest. Thus, ATP consumption must equal ATP use for homeostasis to be maintained. Diet is a paramount manipulator of the skeletal muscle utilization of ATP when exercising and recovering

Microbiological transformation of steroids

Microbiological transformation of steroids 1. Introduction 1.1. Microbiological transformation of steroids. Steroids are small organic molecules that are synthesized in steroidogenic tissues and act on target sites to regulate a cascade of physiological functions [1]. Examples of natural occurring steroids include: sterols, steroidal saponins, cardioactive glycosides, bile acids, corticosteroids and mammalian sex hormones [2]. They are based on the steran skeleton which is composed of three six-carbon ring units and one five-carbon ring unit. The rings are labelled A, B, C, and D beginning from the far left (see fig. 1). In naturally occurring steroids, all four rings are in the chair conformation [3] with rings B, C, and D in trans- configuration with respect to each other. For rings A and B the position of the C-19 methyl group attached to C-10 and the hydrogen attached to C-5 determines the structure and their cis-/trans- configuration. Overall, neighbouring substituent are trans- if they are diaxial or diequatorial like in fig. 1a, and are cis- if they are axial-equatorial (fig. 1b). However, the two methyl groups attached to C-10 and C-13 are always axial in relative to rings B and D, with C-10 substituent being the conformational reference point [3]. Hence, the 5ÃŽ ±- steroid skeleton (see fig. 1a) is in the trans-trans-tans- configuration, and thus is broadly planar. The knowledge of the stereochemistry of steroid molecules is highly significant in understanding its biotransformation reactions which is the basis of this study. Steroids represent a class of natural products with diverse therapeutic properties. It has been observed that minor changes in the molecular structure of steroids can affect their biological activity [4,5]. Hence numerous research have been conducted to improve the activity of existing steroid compounds and to synthesize novel steroidal compounds with pharmacological activity, and thus the most significant area of these research is the transformation of steroids using biocatalysts. Biotransformation could be defined as the modification of an organic compound into a recoverable product by chemical reactions catalysed by enzymes originating from a biological system [6]. It should be noted that the organic compound which is the substrate is not involved in the primary or secondary metabolism of the biological system concerned, and thus distinguishes this process from biosynthesis. The biotransformation of steroids is one of the most important microbial processes that are highly regio- and stereospecific, involving chemical modifications (e.g. oxidation, reduction, hydrolysis, isomerisation, epoxidation, etc.) to the parent steroid which are catalysed by the microbial enzymes. In addition, the features which govern their regiospecificity differ from those controlling chemical specificity, and so it is possible to obtain biotransformation at centres that are chemically unreactive [6]. For example, in the study conducted by Peterson and Murray using Rhizopus arrhizu s, it was observed that progesterone was hydroxylated at C-11 which is an ureactive site in this steroid molecule [7]. Therefore, these characteristics alongside the rapid growth and high metabolic rates of microorganisms give biotransformation reactions an advantage over conventional chemical processes as a tool in the production of therapeutic agents (e.g. anti-inflammatory, diuretics, anabolic, contraceptive, anti-cancer, anti-androgenic, postgestational etc.) in the pharmaceutical industry. The ever growing research into the study of microbial transformation of steroids have led to newer technology in this area of science such as: genetically modification of microorganisms to improve their steroid transforming capabilities, the immobilization of whole cells or isolated enzymes in a suitable matrix for repetitive economic utilization of the enzymes, manipulation of culture media to improve product yields by the use of enhancers e.g. cyclodextrin, and the improvement of the solubi lity of substrates are insoluble (or sparingly soluble) in water [8]. Furthermore, the advances in microbial steroid biotransformation have led to the discovery of new microbial reactions and novel metabolites which may be of interest within academia and clinical medicine. 1.2. The mechanism of Hydroxylation The hydroxylation of a compound is a very important metabolic process, in humans; this process is catalysed by cytochrome P450 enzymes and results in products with a higher polarity than the parent compound, and thus aiding its excretion from the body [1,3]. The process of hydroxylation, involves the conversion of a carbon-hydrogen to a carbon-hydroxyl bond, and when catalysed by the enzyme hydroxylase, the reaction is more regio- and stereospecific in contrast to the conventional chemical process [8-12]. As a result, microbial hydroxylation is rather used for the synthesis of hydroxysteroid. Fungal hydroxylation of steroids continues to be the focus of attention at different levels of research and product development. In spite of its popularity this process is not fully understood because few studies have been conducted on the hydroxylase enzyme due to the difficulty in isolating this enzyme [10,11]. However, most studies have shown that the cytochrome P450 enzyme is also responsible for steroid hydroxylation in filamentous fungi [9-11,13,22]. Cytochrome P450 (CYP 450) enzyme is an iron-haem system which carries out a wide range of biocatalytical transformation. These enzymes are also known as monooxygenases because they transfer one atom of molecular oxygen to an organic substrate. The catalytic mechanism for this reaction involves the binding of the substrate to the active site of the enzyme and then the displacement of a water molecule (see fig.2). This is followed by a reduction of the iron in the CYP 450-haem complex to its ferrous state (Iron II) by an electron transfer. The ferrous state then binds to molecular oxygen to form a ferrous-dioxy (Iron (III)-OOH) species. This species then loses a hydroxyl anion to form an iron (IV)-oxygen radical. This radical may withdraw a hydrogen atom from the substrate to generate a carbon radical and an iron (IV)-hydroxyl species. The carbon radical then accepts a hydroxyl radical from the iron (IV)-hydroxyl species to form a hydroxylated product and iron (III). A simple general reaction equation for this process is summarised below: (where R represents the substrate and NADPH is the electron transferring species). RH + NADPH + H+ + O2 → ROH + NADP+ + H2O In other to fully understand the mechanism of fungal hydroxylation of steroids, the relationship between the structure of the CYP 450 hydroxylase enzyme and its regio- and stereoselective characteristic has to be defined. However, as mentioned earlier not much studies have been conducted on the structural features of this enzyme, and so active site models was developed to grasp the concept of the regio- and stereoselective outcome of microbial hydroxylation reactions. The first model, postulated by Brannon et al suggested the possibility for a steroidal substrate to be bound by a single steroid hydroxylase in more than one orientation due to two- sites binding, which could result in hydroxylation taking place at more than one position given the appropriate geometrical relationship between the active site of the enzyme and the carbon atom of the substrate undergoing the reaction [9,14]. These four orientations are represented as normal, reverse, inverted and reverse inverted (see fig. 3) and has been observed in the metabolic handling of 3ÃŽ ²-hydroxy-17a-oxa-D-homo-5ÃŽ ±-androstan-17-one by a filamentous fungus; Aspergillus tamarii [15]. The other model, Jones model takes into account only the normal and reverse binding orientations [6]. It requires the existence of three active centres on the steroid hydroxylase enzyme. These active centres have dual roles and could act both as a binding site or a hydroxylating site [16]. However, these roles are mutually exclusive, and so hydroxylation would occur at the closest nuclear centre to the steroid. Hence the enzyme-substrate interaction proposed by Jones would suggest a triangular location with an approximate spatial correspondence to C-3, C-11 and C-16 atoms of the steroid nucleus [6] (fig. 4). This model could not explain the hydroxylation reactions by some microorganisms. Therefore another theory was developed by McCrindle et al using both models above and taking into account the 3- D nature of the steroid compound and hydroxylase enzyme [17]. In this model, the steroid ring acts as a planar reference point (fig. 5). Binding site A favours oxygen atoms below the plane of the ring and hydroxylation is alpha. Binding site B is similar to A but can also hyroxylate alpha (axial or equatorial) or beta (equatorial) atoms. Whereas, binding site C binds preferentially to oxygen atoms above the plane of the steroid ring and hydroxylate with -beta orientation. Overall, this model tends to fit the hydroxylation pattern of most microorganisms. The hydroxylation outcome of some steroids can be predicted based on the oxygen functions or directing groups on the steroid skeleton. As a rule of thumb mono- oxygenated substrates are dihydroxylated and their transformation products are often in low yields [16]. This is as result of the presence of one oxygen function on the steroid compound making it less polar and thus decreasing its solubility which hinders its permeation into the microbial cell. In addition to this, the presence of only one oxygen function allows the steroid to bind to the enzyme at only one centre, thereby increasing its rotation and oscillation about the active site which makes it more likely to be dihydroxylated. Whereas, di- oxygenated substrates are monohydroxylated because the presence of two oxygen functions reduces the chance of multiple hydroxylations due to the reduction in the possible number of binding orientations [16]. Furthermore, the presence of two binding oxygen groups increases the rate of r eactivity of microbiological transformation as the increased substrate polarity improves solubility and thus permeation into the cell membrane of the microorganism is very likely. A wide variety of organisms have shown this pattern of hydroxylation with a wide range of substrates [15,16]. Hydroxylated steroids possess useful pharmacological activities, for example, C-11 hydroxylation is regarded as essential for anti- inflammatory action, and 16ÃŽ ±- hydroxylated steroids have increased glucocorticoid activity [8,12]. Hence the steroid industry exploits the use of 11ÃŽ ±-, 11ÃŽ ²-, 15ÃŽ ±- and 16ÃŽ ±- hydroxylation mainly for the production of adrenal cortex hormones and their analogues [8]. A range of microorganisms have been observed to affect this type of hydroxylations. For example, 11ÃŽ ±- hydroxylation is performed using Rhizopus sp. Or Aspergillus sp., Cuvularia sp. or Cunninghamella sp. and Streptomyces sp. generates 11ÃŽ ²- and 16ÃŽ ±- hydroxylations respectively [8,18]. Further research has shown other hydroxylations (e.g. 7ÃŽ ±-, 9ÃŽ ±- and 14ÃŽ ±- hydroxylations) of having the potential for industrial exploitation [18]. 1.3. The mechanism of Baeyer- Villiger Oxidation Baeyer- Villiger oxidation is the oxidative cleavage of a carbon-carbon bond adjacent to a carbonyl, which converts ketones to esters and cyclic ketones to lactones [19,20]. The mechanism of this chemical process was originally proposed by Criegee [19]. It involves a two step process: a nucleophillic attack of a carbonyl by a peroxo species resulting in the formation of a Criegee intermediate, which then undergoes rearrangement to the corresponding ester. Commonly used peracids or oxidants include: m-chloroperoxybenzoic acid, hydrogen peroxide, peroxyacetic acid and trifluoroperoxy acetic acid. This chemical process is highly significant, because the products generated are compounds which are intermediates in the synthesis of natural products or bioactive compounds. However, the oxidants used in chemical Baeyer- Villiger oxidation (BVO) are expensive and hazardous and also the reaction generates a large amount of waste products [4]. Hence biological (or enzymatic) BVO offers a green er approach for the production of chiral lactones. Biological Baeyer- Villiger oxidations are mediated by flavin- dependent monooxygenase enzymes i.e. Baeyer- Villiger monooxygenases (BVMOs) [19,21,22]. As a result of the versatile nature of flavoproteins [19], BVMOs have been shown to perform a variety of catalytic reactions including BVO of steroidal systems. The mechanism of microbial Baeyer- Villigers oxidation (fig. 6) is based on results obtained with cyclohexanone monooxygenase (CHMO) isolated from Acinetobacter calcoaceticus [19,22]. This enzyme was shown to possess flavin adenine dinucleotide (FAD) as a prosthetic group and was also found to be dependent on NADPH and oxygen. The enzymatic process is initiated by the reduction of the tightly bound FAD by NADPH followed by rapid oxidation by molecular oxygen to produce flavin 4a- peroxide anion, which acts as the oxygenating species. Nucleophillic attack of the substrate carbonyl group by the flavin 4a- peroxide anion results in the Criegee intermediate. This intermediate then undergoes rearrangement to form the product lactone and 4a- hydroxy- flavin. The catalytic cycle is terminated by elimination of water to form FAD and the release of the product and co-factor. It should be noted that the mechanism for microbial BVO based on CHMO serves as a model for other BVMOs. However, ther e are some differences such as the co-factor NADPH can be replaced by NADH and the prosthetic group FAD can be replaced by FMN [19]. Overall, there are no significant changes to the mechanism. Microbial Baeyer- Villigers oxidation is highly regio- and stereoselective [4,19-22] and as result it is commonly utilized for the biotransformation of steroidal compounds. It has also been shown in various studies, the ability of microbial BVMOs to attack the different ring systems of the steroid skeleton. Glomerella fusarioides was observed to biotransform eburicoic acid through an attack on the ring- A system by way of BVO to form a lactone, followed by a ring- cleavage to produce carboxylic acid [19]. In addition, 3-ketosteroids were observed to undergo Baeyer- Villigers oxidation with an isolated Baeyer- Villiger monooxygenase enzyme from Pseudomonas sp. attacking the C-3 ketone group on ring- A [4]. Ring- B lactone formation has also been observed in the steroid system using tomato cell suspension cultures to produce 24- epibassinolide [19]. Ring- D lactonization is very common and has been demonstrated by quite a few fungal species such as Pencillium sp., Cylindrocarim sp., M ucor sp. and Aspergillus sp. These fungi were able to biotransform progesterone to testololactone by way of Baeyer- Villigers oxidation via the intermediate steroid androst-4-ene-3,17-dione [19]. So far, ring- C lactonization has not been observed, although studies have been conducted to view this ring attack but none have proven its possibility [4]. Overall, several research have been undertaken and are still been conducted to explore the catalytic repertoire of Baeyer- Villiger monooxygenase enzymes, and these studies have shown the ability of this enzyme to catalyse the oxidation of 3- keto and 17- keto steroids with full control of the regiochemistry of the produced lactone thus allowing its application as an alternative to the conventional chemical process. 1.4. The mechanism of alcohol oxidation Alcohol oxidation is an important reaction in organic chemistry. It leads to the production of aldehydes or carboxylic acids from primary alcohol and ketones from secondary alcohol. Tertiary alcohols are resistant to oxidation because it is impossible to remove a hydrogen ion or add an oxygen atom to the compound without breaking the C-C bond. The commonly used reagents for the oxidation of alcohol are Jones reagent, potassium permanganate and chromium- based reagents. However, the oxidation of primary alcohols to aldehydes creates a problem for the organic chemist because aldehydes are not stable when produced in the conventional chemical oxidation process thus the use of microbial cells is preferred to overcome this problem [22]. The enzymes used in the oxidation of alcohol by microorganisms are alcohol dehydrogenases (ADH) which are dependent on the co-factors NAD+ or NADP+. The mechanism of this reaction consists of a series of equilibrium where the hydride from the alcohol subs trate is transferred to NAD(P)+ in the ternary complex enzyme- NAD+- alcohol complex [22]. In humans, this process is carried in the same fashion and is extremely important for several endogenous as well as drug metabolism. Therefore, microorganisms could serve as models for human metabolism using this process. An unprecedented level of regioselctivity of microbial oxidation of the alcoholic group in bile acids has been observed [23]. Some fungal species are known to have the ability to oxidise the C-3 and C-17 hydroxyl groups of steroidal compounds. Aspergillus tamarii has been shown to possess the enzyme 3ÃŽ ²- hydroxy- steroid- dehydrogenases which catalyses the 3ÃŽ ²- hydroxyl group to a C-3 ketone [5]. Oxidation of the 17ÃŽ ²- hydroxyl group has also been observed in a number of fungal species e.g. Penicillium sp., Aspergillus sp. and Mucor sp [24,25]. In general, a number of microorganisms have shown the ability to oxidise the alcohol groups on a steroid compound to generate t he ketone analogue, which could serve as an intermediate in the synthesis of lactones. 1.5. The mechanism of carbonyl reduction The reverse reaction of oxidation is reduction. It involves the transfer of one hydride ion to the carbonyl group. In conventional chemical reaction, the catalysts commonly used are sodium borohydride (NaBH4) and Lithium aluminium hydride (LiAlH4), aldehydes are easily reduced to primary alcohols using these catalysts. However, the high stereoselective reduction of ketones to chiral secondary alcohols is better performed with microbial enzymes [20,22]. This process is catalyzed by alcohol dehydrogenases (ADHs), requiring the co-enzymes NADH or NADPH which transfers the hydride ion to the Si- or Re- face of the carbonyl group resulting in the formation of the corresponding (S)- or (R)- alcohol [22,25]. Microbial reduction of ketones to secondary alcohols normally proceeds in accordance with Prelogs rule to give secondary alcohols in the main (S)- enantiomer [25,26]. However, only a very limited number of microbial enzyme (ADHs) is available to allow anti- Prelog activity and have bee n demonstrated in the fungus Myceliophthora thermophila [27]. The ability of microorganisms to reduce the carbonyl groups on steroid compounds was reported in 1937 by Mamoli and Vercelloni who described the reduction of the 17- keto group in androst-4-ene-3,17-dione to testosterone by Saccharomyces cerevisiae [25]. Since then this process has been demonstrated for a wide variety of substrates and microorganisms of different species. Carbonyl reduction often accompanies other reactions in steroid biotransformation, and thus acts as one of the processes in the production of hydroxysteroids. 1.6. The microorganism: Myceliophthora thermophila Thermophilic fungi are among the few fungal species of eukaryotic organism that are able to survive at temperatures as high as 60 62oC [28]. However, Cooney and Emersons definition of thermophilic fungi is: fungi that have a growth temperature minimum at or above 20oC and a growth temperature maximum at or above 50oC [29]. These fungi have a widespread distribution in both tropical and temperate regions, inhabiting various types of soil and places where decomposition of plant material and organic matter occur thus providing the warm, humid and aerobic environment which are the basic conditions for their development [28,29]. The enzymes of thermophilic fungi have been studied to explore their contribution in biotechnology, and these studies have identified a remarkable range of extracellular enzymes (e.g. proteases, lipases, ÃŽ ±-amylases, glucoamylases, cellulases, cellobiose dehydrogenases, xylanases, ÃŽ ±- D-glucuronidase, polygalacturonase, laccases, phytase and D-glucosyltransf erase) and intracellular enzymes (e.g. trehalases, invertases, ÃŽ ²-glycosidases, lipoamide dehydrogenases, ATP sulfurylases and protein disulfide isomerases) [28]. The majority of these enzymes are appreciably thermostable which have resulted in its application in sugar and paper industries [30]. So far only two studies to date have been conducted to investigate the steroid biotransformation abilities of thermophilic fungi. The first study used the thermophilic filamentous fungus, Rhizomucor tauricus and it was observed that all transformations were oxidative producing mono- and dihydroxylated products with allylic hydroxylation been the predominant route of attack on the steroid compounds [30]. The second study was conducted using Myceliophthora thermophila [27] on which this present study is based. Myceliophthora thermophla is a thermophilic filamentous fungus classed as an ascomycete within the phyla of fungi [28]. It has another name which is sometimes used, Sporotrichum (Chrysosporium) thermophile [28,29]. However, M. thermophila is the sexual (telomorph) stage of the fungi, while Sporotrichum (Chrysosporium) thermophile is the asexual (anamorph) stage [28]. Its main habitat is in the soil and it is found in the following countries: USA, Canada, India, UK, Japan and Australia [29]. But this fungus can grow on simple media containing carbon, nitrogen and essential mineral salts such as Czapek- dox agar (CDA). The optimum growth temperature for M. thermophila is within the range 45 50oC [28]. It grows rapidly on CDA at 45oC, producing colonies that vary in surface texture from cottony to granular and its colour changes from white to cinnamon brown [29]. This fungus has also been observed to generate extracellular enzymes such as laccases, xylanases, cellulases and phytase wh ich have been exploited for use in the food industry and as biocatalyst in biotechnological processes [27]. This present study is a continuation of the research into steroid biotransformation by M. thermophila. Previously, a series of steroids (progesterone, testosterone acetate, 17ÃŽ ²-acetoxy-5ÃŽ ±-androstan-3-one, testosterone and androst-4-ene-3,17-dione) were incubated with this fungus, and a wide range of biocatalytical activity was observed with enzymatic attack at all four rings of the steroid nucleus and the C-17ÃŽ ² side- chain. This fungus demonstrated an unusual ring- A opening following incubation of the steroid 17ÃŽ ²-acetoxy-5ÃŽ ±-androstan-3-one, and thus generating 4-hydroxy-3,4-seco-pregn-20-one-3-oic acid. It was also identified to be the first thermophilic fungus to cleave the side- chain of progesterone. M. thermophila also demonstrated reversible acetylation and oxidation of the 17ÃŽ ²- alcohol of testosterone [27] (fig. 8). Further investigation into the diverse biocatalytical activity of this organism has led to the incubation of six saturated steroids namely: 17ÃŽ ²-hydroxy-5ÃŽ ±-androstan-3-one, 5ÃŽ ±-prgnane-3,20-dione, 3ÃŽ ²-hydroxy-5ÃŽ ±-androstan-17-one, 3ÃŽ ±-hydroxy-5ÃŽ ±-androstan-17-one, 5ÃŽ ±-androstan-3,6,17-trione and 5ÃŽ ±-androstan-3,17-dione with M. thermophila 1.7. Hypothesis The proposed hypothesis from previous study is outlined as follows: * Presumed lactonohydrolase activity evident from the isolation of an open lactone ring. * Enzymes responsible for the reduction of C3 ketone to a 3ÃŽ ±- alcohol and hydrogenation of the C-4-C-5 alkene are induced by progesterone. * Organisms ability for reverse metabolism, which is evident from the acetylation of testosterone to generate testosterone acetate and the reduction of the C-17 ketone of androst-4-ene-3,17-dione to produce testosterone which further undergoes acetylation. * Preference for stereochemistry of hydroxylation with attack at axial protons (6ÃŽ ², 7ÃŽ ±, 11ÃŽ ², 14ÃŽ ±). Therefore, the main aim of this study is to observe the effect of saturated steroids on the biocatalytical activity of Myceliophthora thermophila CBS 117.65 and to prove the hypothesis from the previous study.

Year without Oil :: essays papers

Year without Oil OPEC Oil Embargo There are several things that come to mind when presented with the picture and topic, but the one that stands out most is shortage. However, shortage is an ironic word to use for it. It wasnÕt really a shortage in the fact that the world is out of oil, which being a non-renewable resource will be one day, but it was an incredible 130% increase in price by OPEC, Organization of Petroleum Exporting Countries. This forced the petroleum market to head into a tailspin. OPEC, started by the major oil producing countries in the Middle East, was designed to give price control to the oil producers, instead of the oil manufacturers. Formed in 1960, OPEC was only a middleman for 10 years, but in the 1970Õs, they found the right time to drive up the price of gas. One viewpoint can say it was about time that we started paying these countries for what they were up to that point, "giving us," but from the other standpoint, OPEC is no more than a cartel and monopoly. A cartel is two or more parties, the oil producing countries, hurting an innocent third party, oil consumers. OPEC was created to hurt the oil manufacturers who were taking advantage of the oil producers, but unfortunately the one that got hurt from the agreement are the oil selling stations and us, the consumer. There are several reasons why it isnÕt the manufacturers didnÕt get affected by any of the price raises. First of all, no matter how high the price of crude oil goes, the world still has to keep buying oil products. In fact, the world is using more petroleum products now than it ever has before, and can only get it from a few manufacturers, which means a monopoly is feeding an oligopoly. Monopolies are when the economy relies on one source for all of a product, also called a trust. Monopolies are banned in the United States by Anti-Trust Laws. Oligopolies are products, that the economy relies on, that are only available from a few sources. In a large market, the oil market, these companies can raise prices for consumers and receive massive increases in their profits. "To really understand the hardships that happened in the 1970Õs, and not being around in that time, we can look at the situation we are experiencing today.