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Outline Change of enzyme quantity Major differences between change of enzyme quantity and change of enzyme quality Isoenzymes Synthesis and degradation of enzymes Change of enzyme quality Allosteric regulation Covalent modifcaiton Proteolytic activation Activation or inhibition by regulatory proteins Association and disassociation Regulation of enzyme levels requires either an increase in the synthesis of the enzyme, or a decrease in the rate of its degradation (or the rate of the degradation of the mRNA that encodes the enzyme). Increasing protein synthesis is an expensive proposition, it takes 4 ATPs just to form one peptide bond. That’s 1 200 ATPs for one 300 amino acid protein! Because regulation of enzyme activity does not usually involve protein synthesis, the amount of energy necessary is relatively small compared to other cellular functions. The notable exception to this general rule is regulation by protein inhibitors, which generally bind very tightly to their enzyme targets and must be digested to be removed. Isozymes are physically distinct forms of the same enzyme. Isozymes may differ from each other by differences in their amino acid sequences or by the presence of different posttranslational modifications in each isozyme. The relative abundance of different isozymes varies for different tissues. The ability to control which isozymes are expressed in a particular cell allows each cell to adjust the enzyme activity based on the specific conditions that exist in the cell. Isozymes: An automotive analogy Lactate Dehydrogenase (LDH) is composed of four monomers Each monomer can be either heart or muscle type Five different isozymes of LDH exist: H4, H3M, H2M2, HM3, and M4 All of the LDH isozymes catalyze the interconversion between lactate and pyruvate Each isozyme of LDH can be separated by chromatography Different tissues have different levels of each of the LDH isozymes During myocardial infarction, endothelial cells rupture, releasing their
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