生物化學原理課件（英文）：Chapter12 Regulation of enzyme activity

1、Chapter 12 Regulation of Enzyme Activity Outline Change of enzyme quantity 1.Major differences between change of enzyme quantity and change of enzyme quality 2.Isoenzymes 3.Synthesis and degradation of enzymes Change of enzyme quality 1.Allosteric regulation 2.Covalent modifcaiton 3.Proteolytic acti

2、vation 4.Activation or inhibition by regulatory proteins 5.Association and disassociation Enzymes need to be active in the right place at the right time N Inappropriate expression can lead to uncontrolled growth or cell (and organism) death How do cells control specific biochemical reactions? Contro

3、l of enzyme activity Control of enzyme levels Control of enzyme location Control of substrate availability Removal or conversion of reaction products slow response time energetically expensive maximum activity limited only by relative rates for protein synthesis and degradation generally used for lo

4、ng term changes in enzyme activity Change of enzyme quantity - Regulation of enzyme levels Change of enzyme quantity - Regulation of enzyme levels Change of enzyme quality - Regulation of enzyme activity Jrapid, allows immediate response to stimuli Jlow energy expenditure required Jmaximum activity

5、is limited by amount of enzyme available Change of enzyme quality - Regulation of enzyme activity 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 modification

6、s 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. What is an isozyme? Isozymes:

7、 An automotive analogy H HH H M HH H M MH H M MM M MH Heart typeMuscle type M MM H 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 interconve

8、rsion 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 contents into the bloodstream. This increases the serum levels for LD

9、H isozymes 1 and 2 and can be used as a diagnostic tool. M4 M3H M2H2 MH3 H4 Quality control can be achieved by five different mechanisms 1.Allosteric control 2.Covalent modification 3.Proteolytic activation 4.Stimulation or inhibition by control proteins 5.Monomer Multimer Allosteric = “other site”

10、other than active site Regulatory molecules called, effectors, modulators,regulatory molecules Homotropic regulation: regulation by substrate at active site Heterotropic regulation: regulation by molecule NOT substrate ( end products), at allosteric site Few enzymes are allosteric D partially inhibi

11、ts A - B Cooperative enzymes can be allosterically regulated Reaction rate Allosteric regulators do not bind to the active site of the enzyme Activation or inhibition of an enzymes activity due to binding of an activator or inhibitor at a site that is distinct from the active site of the enzyme. All

12、osteric activators stabilize the high affinity state of the enzyme Allosteric inhibitors stabilize the low affinity state of the enzyme Allosteric regulators shift the substrate dependence curve In the above plot, the allosteric activator decreases the Km of the enzyme, while the allosteric inhibito

13、r increases the Km of the enzyme. Reaction rate Noncooperative enzymes can also be allosterically regulated Reaction rate Covalent modification regulates the catalytic activity of some enzymes Inactive Active Phosphorylation - an example of regulation by reversible covalent modification of the enzym

14、e Protein kinases catalyze the phosphorylation of proteins Protein phosphatases remove phosphate groups from phosphorylated proteins Reversible Phosphorylation of Proteins Some enzymes are activated by proteolytic cleavage of a peptide bond Activation of chymotrypsinogen exemplifies proteolytic acti

15、vation -Chymotrypsin (active) p p-Chymotrypsinogen (inactive) p p-Chymotrypsin (inactive) S SS S S SS S S SS S Regulation of digestive enzymes Pepsinogen is converted to pepsin by autocatalytic proteolysis at pH 2 Zymogen Pepsinogen Chymotrypsinogen Trypsinogen Procarboxypeptidase Proelastase Prothr

16、ombin Fibrinogen Factor VII Factor X Proinsulin Procollagen Procollagenase Active Enzyme Pepsin Chymotrypsin Trypsin Carboxypeptidase Elastase Thrombin Fibrin Factor VIIa Factor Xa Insulin Collagen Collagenase Function protein digestion protein digestion protein digestion protein digestion protein d

17、igestion blood clot formation blood clot formation blood clot formation blood clot formation plasma glucose homeostasis component of skin and bone remodeling processes during metamorphosis, etc. Enzymes involved in protein digestion, blood clotting, and tissue and bone remodeling are synthesized in an inactive conformation, then activated by proteolytic cleavage Stimulation and inhibition by control proteins Serpins - An example of inhibition by control proteins Elastase is inhibited by 1-antitrypsin Cigarette smoking oxidizes Met 358 of 1-antit