Sphingomyelinase Essay Example | Topics and Well Written Essays - 1250 words

Sphingomyelinase - Essay Example These enzymes have been categorized into six different classes namely Mg+ dependant neutral SMase, Mg+ independent neutral SMase, acid SMase, secretory SMase, and alkaline SMase and bacterial SMase (Goni and Alonso 38). This paper mainly discusses the mode of action and medical importance of neutral SMase. Two neutral SMase have been determined in mammals. Mg+ dependant nSMase 1 is concentrated in kidneys while Mg+ independent nSMase 2 is mostly present in golgi bodies of brain (Mizutani et al. 3727). In mammals, nSMase acts as an integral membrane protein whereas in bacteria they are soluble proteins. They play an important role in the human body by catalyzing the production of ceramide and regulate a number of metabolic events such as cellular differentiation, arrest of cell cycle and apoptosis (Mizutani et al. 3727; Gallardo et al. 1305). The mechanism of nSMase has mostly been studied on the enzyme obtained from Bacillus Cereus. Their working has been described as a divalent meta l-ion dependant manner (Ago et al. 16157). The enzyme obtained from the bacteria is quite similar to the mammalian nSMase in its action and function. The active site of nSMase is comprised of a glutamic acid (Glu) residue and histidine (His) residue, both of which are bound to either one or two metal cations, usually Co+ or Mg+. These cations support the action of SMase by recruiting sphingomyelin towards the active site. The cation at the Glu residue acts on the region between C1 and the phosphate group of sphingomyelin by interacting with amido-oxygen and ester-oxygen. On the other hand the cation at the His residue combines with the oxygen atom of the phosphate group of sphingomyelin resulting in a stabilized phosphate group. Furthermore this interaction activates a water molecule by lowering the value of acid dissociation constant of one of the bridged water molecules. This activation allows water molecule to attack the phosphate group of sphingomyelin as a nucleophile. Later th e reformation of phosphate group in its tetrahedral shape results in the formation of the two products; ceramide and phosphorylcholine. One of the commonest of disease associated with sphingomyelinases is Niemann-Pick disease. An autosomal recessive lysosomal storage disease, it is caused due to mutation in either SMPD1 gene or NPC1 gene and is classified into three types; A, B and C. Symptoms are characterized according to the organ of accumulation. This disorder occurs when there is deficiency of sphingomyelinases leading to a stop in the degradation pathway of lipids and resulting in accumulation of sphingomyelin within the lysosomes of affected cell causing them to become enlarged. This along with many small vacuoles renders a foamy appearance to the affected cell. Pharmacologically, there are no reported drugs which are synergistic in action to sphingomyelinases, although a number of researches have now appeared which discuss the inhibitors of sphingomyelinases (Canals, Perry, Jenkins and Hannun 694). Scyphostatin, which is attained from the mycelia extracts of Trichopezia mollissima has emerged as a neutral sphingomyelinase inhibitor (Czarny and Schnitzer 1344). As ceramide is understood to be a second messenger molecule working like inflammatory mediators (TNF?, IL-1, IL-6 and LPS) it is believed that scyphostatin

A 2,500 3,000 word individual report Essay Example | Topics and Well Written Essays - 1750 words

A 2,500 3,000 word individual report - Essay Example Finally, we look into how we can implement Performance Management to improve the company to better achieving its long term goals. The purpose of this section is to define Performance Appraisal and Performance Management, as well as to distinguish between the two. Both Performance Appraisal and Performance Management lead to increase in organisational productivity (Thomson 2003). Performance Appraisal is one of the tools used for implementing Performance Management. Performance Appraisal is the process of setting job standards, measuring and evaluating employee performance, and giving relevant feedback to the employees (Thomson 2003). Performance appraisals are an important part of performance management, particularly in the Feedback Stage of Performance Management (Farrington 2007). Currently, our company is relying on Performance Appraisal in order to improve employee performance. However, Performance Appraisal is not enough to maximize and maintain good employee performance for the following reasons. Performance Appraisal, when used alone, is demotivating, it takes a lot of time to implement and get results back, it creates a legal liability, and it flies in the face of team rewards and accountability (Brull 1997). Furthermore, Cook discusses that the focus of Performance Appraisal is too much on the individual, instead of developing the employee. Appraisal is inconsistent and only useful in the extremes of performance (1993). In itself, it is therefore not enough to maximize organisational productivity. This section defines Performance Management, its two foci which are development and reward driven, and details the process of performance management. This section then explains how and why Performance Management improves organisational productivity. Performance Management is the process used by managers to enable the employees to perform effectively and efficiently