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Unformatted text preview: 9-1Cell and Molecular Biology (Biol. Chem. 410A)Lecture #9Harry R. Matthews, Ph.D.October 8, 1996Properties of Enzymes IIClinical correlations:leukemiaenzyme assay in the clinical labLearning objectives:initial velocityMichaelis-Menten equationKM, Kcat2-substrate reactionsenzyme assayOptional reading:Stryer IV: Chapter 8eukemia is a deadly cancer of white blood cells. Leukemia cells are more de-pendent on asparagine in the blood stream than other blood cells are. Hence, re-ducing the asparagine levels in the blood is a good treatment for leukemia. The pharmacolo-gical approach is to degrade free asparagine in the blood by the use of the enzyme aspar-aginase. Asparaginase can be isolated from many different bacterial sources and initial results with asparaginase treatment of leuk-emia were very variable. More careful analys-is showed that the variation was due to the kinetic characteristics of the different aspar-aginase preparations used and that the effic-acy of any particular preparation could be ac-curately predicted from a simple kinetic ana-lysis of the asparaginase activity in the labor-atory.LWe have seen that the body is constantly adjusting the rates of the reactions it cata-lyzes. We have looked at the methods used to control the key regulatory enzymes in particu-lar pathways. In this lecture we move on to consider the regulation of the majority of en-zymes, the ones that are not subject to allos-teric regulation. While such enzymes may not be the targets of regulation in the normal body, they are very often the targets of clinical therapy. For example, the enzymes that are inhibited by the chemotherapy drugs, fluor-ouracil or methotrexate, in the pathway to the formation of TTP are not the major rate limit-ing steps in the normal synthesis of TTP. The rate limiting enzyme under normal conditions is the allosteric enzyme ribonucleotide re-ductase. How, then, can pharmacological in-hibitors of thymidine kinase or dihydrofolate reductase affect the rate of production of TTP? To answer this question, and to understand some important parameters of clinical enzyme assays, we need to look at the kinetics of en-zyme reactions.Kinetics are concerned with the rates of re-actions. This is a very important matter for the body which maintains its steady state by adjusting reaction rates in response to the en-vironment and to hormonal controls. We will start by considering the rates of chemical re-actions in isolated systems and then consider how we use this understanding to work with enzymes in the body....
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This document was uploaded on 06/17/2011.
- Spring '03