Enzyme inhibition, therapy

Keywords Bioorganic chemistry, Cellular signal transduction, Enzyme-Inhibition, Ras-farne-syltransferase, Tumor-therapy... 

Bjorck JE. (1999) Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension The Captopril Prevention Project (CAPPP) randomised trial. Lancet 353 611-616. 

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. ... 

Vitamin K antagonists, such as dicoumarol (8.61, a natural product) and warfarin (8.62), are used as anticoagulants in human therapy (thrombosis, atherosclerosis) and as rat poisons that lead to internal bleeding and death in rodents. Heparin, a polysaccharide consisting of 2-0-sulfonated glucuronic acid and 2-N,6-0-disulfonated glucosamine, is also a widely used anticoagulant, but its effect is connected not with Vitamin K but with enzyme inhibition. 

Standard therapy of OP poisoning consists of the administration of a combination of atropine, oxime, and diazepam with other supportive measures when necessary. However, the possibility of addition of purified enzymes such as AChE, ChE, CarbE, and A-esterases to this therapeutic scheme has been considered and preliminary experiments in animals have shown much better protective effect after addition of exogenous enzymes. In this respect, protective effects of AChE, ChE, and CarbE are based on formation of covalent conjugates or phosphory-lated enzymes in the stoichiometric ratio 1 1. Capacity for binding of these enzymes is limited by the number of active sites on the enzyme to which OP molecules can be bound. This means that more enzymes have to be administered in order to achieve better detoxification of OPs which may not always be possible due to adverse effects. This can also be infiuenced by differences in the extent of spontaneous reactivation of these enzymes inhibited by OP. 

Hansson L, Lindhohn LH, Niskanen L, Lanke J, Hedner T, Niklason A, Luomanmaki K, Dahlof B, de Faire U, Morhn C, Karlberg BE, Wester PO, Bjorck JE. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension the CaptoprU Prevention Project (CAPPP) randomised trial. Lancet 1999 353(9153) 611-16. 

Navis GJ, de Jong PE, de Zeeuw D. Volume homeostasis, angiotensin converting enzyme inhibition, and lithium therapy. Am J Med 1989 86 621. 

Fleeg JE,de Jong PE, de Zeeuw D. Additive antiproteinuric effect ofangiotensin converting enzyme inhibition and non-steroidal anti-inflammatory drug therapy a clue to the mechanism of action. Clin Science 1991 81 367-372. 

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