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Unformatted text preview: 6-1Cell and Molecular Biology (Biol. Chem. 410A)Lecture #6Harry R. Matthews, Ph.D.October 2, 1996 11:00 a.m.Enzyme Activation and InhibitionClinical correlations:ethylene glycol poisoningpancreatitissurgical muscle relaxantmalathion poisoningmyasthenia gravisLearning objectives:effects of substrate concentrationcompetitive inhibitionallosteric effectorszymogensOptional reading:Stryer IV: Chapter 8he body produces many enzymes. Some are required almost all the time, just to keep us ticking over, such as the en-zymes for energy production. These enzymes, which are needed most of the time in most cells are sometimes termed housekeeping en-zymes. Although housekeeping enzymes are generally present, their activity is regulated up or down according to the needs of the mo-ment in order to keep the body's metabolism in balance. For example, enzymes involved with energy production will increase when en-ergy is required as for exercise and enzymes involved with energy storage will increase when energy is in excess as after a meal. The increase in enzyme activity may be called up-regulation. Conversely, a decrease in enzyme activity may be called down regulation. En-zymes whose activity is not regulated are constitutive.TOther enzymes are required only in specific situations. For example, the enzymes for DNA replication are required only when a cell be-gins its proliferation cycle. Such enzymes may be present at very low levels or be completely absent when they are not required and will be dramatically increased when they are re-quired. In such cases, the enzyme may be said to be switched on or switched off. The body has many ways in which enzyme activity may be regulated. One way is to change the amount of enzyme protein that is present by changing the rate of synthesis or degradation. In other cases, a covalent modi-fication to the enzyme protein will cause the activity to increase or decrease. Alternatively, other molecules may bind reversibly to the en-zyme to change its activity. We will discuss ex-amples of each of these types of enzyme regu-lation as they occur in the body. Some of the most important factors that af-fect enzyme activity are:Change of substrate concentrationChange of product concentrationInhibition by end-product of a pathway (negative feedback)Allosteric activationIrreversible inhibitionAssociation/dissociation of a repressor sub-unit or a specificity-modifier subunitCo-operativityChange of pHChange of ionic conditionsReversible covalent modification of enzymeIrreversible covalent modification of en-zymeChange of enzyme synthesis...
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