Enzyme medical application

Enzymes may also be immobilized by microencapsulation. In this technique, which has medical applications, enzymes are enclosed by various types of semi-permeable membrane, e.g. polyamide, polyurethane, polyphenyl esters and phospholipids. Microcapsules of phospholipids are also called liposomes. The micro-encapsulated enzymes and proteins inside the micro-capsule cannot pass the membrane envelope, but low M, substrates can pass into it, and products can leave. Such encapsulated proteins do not elicit an antigenic response, and they are not attacked by proteases outside the microcapsule. They are therefore suitable for the delivery of enzymes for therapeutic purposes. This area of application is still at an early stage of development, but positive results have been reported from animal experiments and clinical studies, e.g. treatment of inherited catalase deficiency with encapsulated catalase. There are various methods of administration intramuscular, subcutaneous or intraperito-neal injection. However, their major area of application is outside the body. For example, microencapsulated urease can be employed as an artificial kidney in hemodiffusion (Rg.2). 

The enzyme urate oxidase has also found medical application for the treatment of acute hype-ruricaemia (elevated plasma uric acid levels), associated with various tumours, particularly during their treatment with chemotherapy. 

The high specificity of siderophore iron coordination has been extensively explored in iron-chelation therapy for various medical applications, including iron overload diseases, control of iron in specific brain tissues , arresting the growth and proliferation of malaria parasite within their host , as well as arresting the proliferation of cancer cells . Other directions for metal ligation involve enzyme inhibition, which have been demonstrated by the inhibition of urease by coordination of hydroxamate ligand to nickel ions and zinc coordination in matrix metalloprotease (MMP) inhibition by primary hydroxamates. ... 

Conventional ring-opening polymerization of cyclic anhydrides, carbonates, lactones, and lactides require extremely pure monomers and anhydrous conditions as well as metallic catalysts, which must be completely removed before use, particularly for medical applications. To avoid these difficult restrictions, an enzymatic polymerization may be one of the more feasible methods to obtain the polyesters. This method was first reported by two independent groups (Kobayashi [152] and Gutman [153]) who showed that lipases, enzymes capable of catalyzing the hydrolysis of fatty acid esters, can polymerize various medium-sized lactones. 

Rotheim, P. The Enzyme Industry Specialty and Medical Applications, Business Communications Company, Inc. Norwalk, CT, 1994. 

This chapter is divided into two sections. Section 6.1 is concerned with applications of Raman spectroscopy to biochemistry. Related topics to this section are found in Section 3.3.3 of Chapter 3 (SER spectra of dipeptides) and Section 4.1.2 of Chapter 4 (Raman (RR) spectra of peptides, proteins, porphyrins, enzymes and nucleic acids), Section 6.2 describes medical applications of Raman spectroscopy as analytical and diagnostic tools. In contrast to biochemical samples discussed in the former section, medical samples in the latter section contain a number of components such as proteins, nucleic acids, carbohydrates and lipids, etc. Thus, Raman spectra of medical samples are much more complex and must be interpreted with caution. 

Neurotransmitters are removed by translocation into vesicles or destroyed in enzyme-catalysed reactions. Acetylcholine must be removed from the synaptic cleft to permit repolarization and relaxation. A high affinity acetylcholinesterase (AChE) (the true or specific AChE) catalyses the hydrolysis of acetylcholine to acetate and choline. A plasma AChE (pseudo-AChE or non-specific AChE) also hydrolyses acetylcholine. A variety of plant-derived substances inhibit AChE and there is considerable interest in AChE inhibitors as potential therapies for cognition enhancement and for Alzheimer s disease. Organophosphorous compounds alkylate an active site serine on AChE and the AChE inhibition by this mechanism is the basis for the use of such compounds as insecticides (and unfortunately also as chemical warfare agents). Other synthetics with insecticidal and medical applications carbamoylate and thus inactivate AChE (Table 6.4). 

The most important and most studied applications of enzyme biosensors are to detect and monitor blood glucose, followed by lactate, because of the medical applications of such sensors. Thus, by initially detailing the development of glucose biosensors we can better understand and trace the general development of enzyme biosensors containing polymeric electron transfer systems. 

Gregoriadis, G., Medical applications of liposome-entrapped enzymes. Methods Enzymol. 44, 698-709 (1976). 

Enzyme electrodes for medical applications Biosensors Fundamentals, Technologies and Applications ed F Scheiler and R Schmid (VCH) pp 11-8... 

This concept has been extended. Thus the trione (696) rapidly and irreversibly inactivates human erythrocyte nucleoside phosphorylase (PNPase), which catalyzes the reversible phosphorylation of inosine and guanosine to the respective bases and ribose 1-phosphate. Inhibitors of this enzyme have several potential medical applications, for example, in the prevention of foreign tissue rejection, in the treatment of gout and malaria, and for the potentiation of antineoplastic nucleosides. Mechanistically the 5,8-dione (quinone) (696) enters the enzyme active site. An active-site nucleophilic residue subsequently converts the quinone moiety to a hydroquinone by reductive addition (701). The resulting hydroquinone affords an alkylating quinone methide species by elimination of HCl (702) and then traps a second nucleophilic enzyme residue by a Michael type reaction (703). Cross-linking of the active site rationalizes the observed potency <91B8480>. 

At the time of writing, the applications of biodegradable polymers are confined mostly to the field of agriculture, where they are used in products with limited lifetimes, such as mulch films and pellets for the controlled release of herbicides. The synthetic polyesters used in medical applications, principally polylactide and poly(lactide-co-glycolide), while claimed to be biodegradable, are degraded in the body mainly, if not entirely, by chemical hydrolysis. There is little evidence that the hydrolysis of these polyesters of a-hydroxyacids can be catalyzed by hydrolase or depolymerase enzymes. 

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