Farees Enzymology


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Farees Enzymology

  2. 2. OBJECTIVES <ul><li>What are Enzymes </li></ul><ul><li>Hello to Regulatory enzymes </li></ul><ul><li>Types of Regulatory Enzymes </li></ul><ul><ul><ul><ul><li>Allosteric Regulatory Enzymes </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Covalently Modulated Regulatory Enzymes </li></ul></ul></ul></ul><ul><li>Overview the Role of Regulatory Enzymes </li></ul><ul><ul><ul><ul><li>Monoamine Oxidase A </li></ul></ul></ul></ul><ul><ul><ul><ul><li>ADP-Glucose Pyrophosphorylase </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Phosphofruktokinase </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Tyrosine Hydroxylase </li></ul></ul></ul></ul>
  3. 3. ENZYMES <ul><li>They are bio molecules acting as catalysts. </li></ul><ul><li>Protein in nature. </li></ul><ul><li>Accelerating the reactions of living processes. </li></ul><ul><li>Enzymes don’t consume themselves. </li></ul><ul><li>Do’nt change equilibrium but only enhance reaction rate. </li></ul><ul><li>They are highly specific and react with only one substrate to form one product and can enhance reaction rates by as much as 1017 times. </li></ul>
  4. 4. Regulatory Enzymes <ul><li>As the name indicate, it has regulatory function i.e. can undergo a change in catalytic activity. </li></ul><ul><li>OR </li></ul><ul><li>A regulatory enzyme is an enzyme in a biochmeical pathway which, through its responses to the presence of certain other biomolecules, regulates the pathway's activity. This is usually done for pathways whose products may be needed in different amounts at different times, such as hormone production. </li></ul><ul><li>Regulatory enzymes exist at high concentrations so its activity can be increased or decreased with changes in substrate concentrations. </li></ul>
  5. 5. Types <ul><li>Type 1) Allosteric Regulatory Enzymes </li></ul><ul><li>Having two binding sites on its surface. </li></ul><ul><li>The substrate binds to one site, whereas, a metabolite which can be a modulator, binds to the another site. </li></ul><ul><li>The binding of modulator is non covalent and is reversible. </li></ul><ul><li>When modulator binds to allosteric enzyme , enzyme undergoes a conformational change in its structure, because of which enzymes cannot produce its substrate and enzyme activity gets regulated. </li></ul><ul><li>Example: Aspartate transcarbamoylase, an enzyme in pyrimidine synthesis. </li></ul>
  6. 6. Allosteric enzymes undergo conformational changes in response to modulator binding based on its kinetics properties. Based on modulation, allosteric enzymes can be sub-grouped into two categories: <ul><li>Homotropic allosteric enzyme </li></ul><ul><li>In which both the substrate and the effector plays part in the modulation of the enzyme, which in turn affects the enzyme catalytic activity. </li></ul><ul><li>Heterotropic allosteric enzymes </li></ul><ul><li>In which only the effector performs role of modulation. </li></ul><ul><li>At this junction the allosteric site of the enzyme can be one(monovalent) or two and more (polyvalent). </li></ul>
  7. 7. <ul><li>Type 2) Covalently Modulated Regulatory Enzymes </li></ul><ul><li>This type of regulatory enzyme has covalent bond that can interconvert the enzyme in two forms. </li></ul><ul><li>One of the form has more activity and other form has less / negligible activity. </li></ul><ul><li>This interconversion is carried out by another enzyme that can regulate the enzyme activity. </li></ul><ul><li>Example: Glycogen phosphorylase . </li></ul><ul><li>This enzyme has phosphorylase A as active form and phosphorylase B as inactive form. </li></ul><ul><li>Phosphorylase phosphatase and phosphoryl kinase are the enzymes that carryout the inter conversion between these A (active) and B (inactive) forms. </li></ul>
  8. 8. Role Of Regulatory Enzymes <ul><li>Role of regulatory enzyme (MONOAMINE OXIDASE) in Lungs and damage of Smoking </li></ul><ul><li>Most fascinating role of regulatory enzyme in lungs is of Monoamine oxidase (MAO) A which breaks down many compounds that affect blood pressure, and the lung is a major metabolic organ in degrading some of these compounds. </li></ul><ul><li>Cigarette smoking accounts for 440,000 deaths each year in the United States, or nearly one of every five deaths, according to the Centers for Disease Control and Prevention. </li></ul><ul><li>Smoking kills more Americans than AIDS, illegal drugs, alcohol, car accidents, suicides and murders combined and increases one's chances of developing lung, bladder, esophageal and throat cancers; chronic lung diseases; and coronary heart and cardiovascular diseases. </li></ul><ul><li>Smoking appears to reduce MAO A like key enzyme in the lungs. </li></ul>
  9. 9. <ul><li>During investigation of researcher who used positron emission tomography (PET) scanning and a tracer chemical that binds to the specific enzyme monoamine oxidase (MAO A ) to track MAO A levels in nine smokers and nine nonsmokers. </li></ul><ul><li>With whole-body PET imaging, researchers could measure the concentration and movement of the radiotracer and MAO A, a subtype of the enzyme crucial to mood regulation and one that breaks down chemical compounds that regulate blood pressure. </li></ul><ul><li>The scans revealed that MAO A was fairly well &quot;intact&quot; in all of the peripheral organs except in smokers' lungs, said researcher Miss. Fowler. </li></ul>
  10. 10. <ul><li>Smokers had MAO A levels that were 50 percent lower than in nonsmokers, she said, noting that a prior study had also shown a significant reduction of MAO A in smokers' brains. </li></ul><ul><li>So reduced levels of MAO A in smokers' lungs may be a significant factor contributing to some of the physiological effects of smoking, including changes in blood pressure and pulmonary function. </li></ul><ul><li>In conclusion she said that &quot;These studies showing for the first time that smokers have reduced levels of MAO (A) in lungs and MAO (B) in their brains and in certain peripheral organs shed mechanistic light on some of the more puzzling aspects of smoking, including a reduced rate of Parkinson's disease in smokers and a high rate of smoking among people with depression and those addicted to other substances,”. </li></ul>
  11. 11. <ul><li>Role of Regulatory enzyme (ADP-Glucose Pyrophosphorylase), in Bacterial Glycogen Synthesis </li></ul><ul><li>In bacteria and plants, the synthesis of glycogen and starch occurs by utilizing ADP-glucose as the glucosyl donor for elongation of the -1,4-glucosidic chain. </li></ul><ul><li>The main regulatory step takes place at the level of ADP-glucose synthesis, a reaction catalyzed by ADP-Glc pyrophosphorylase (PPase). </li></ul>
  12. 12. <ul><li>Role of regulatory Enzyme the PFK (Phosphofruktokinase)in neural activity maintenance </li></ul><ul><li>Regulatory enzyme the (PHOSPHOFRUKTOKINASE) helps in Glycolysis for maintenance of Synaptic activity (population spikes, PS) and on the level of high energy phosphates in the region of dentate gyrus (DG), CA3 and CA1 area of hippocampal in guinea pigs. </li></ul><ul><li>The sensitivity in maintaining synaptic activity to lowered glucose concentrations showed good parallels with the activity of PFK in these regions, indicating that non-oxidative glycolytic metabolism regulated by PFK is crucial for the maintenance of synaptic activity. </li></ul>
  13. 13. <ul><li>Role of Regulatory enzymes (TYROSINE HYDROXYLASE) in Parkinson’s disease </li></ul><ul><li>The major neuropathology of Parkinson's disease (PD) is the degeneration of nigrostriatal dopamine (DA), resulting in a deficiency of DA, and of the enzyme tyrosine hydroxylase (TH), which catalyzes the synthesis of L-dopa. </li></ul><ul><li>The symptomatic treatment of PD consists of replenishing DA by administering L-dopa, which is enzymatically converted to DA in the striatum. </li></ul><ul><li>The increase of TH activity by modification of the enzyme leads to an increased synthesis of striatal L-dopa, and thereby replenishes the missing DA more efficiently. </li></ul><ul><li>Thus, modification of TH results in an activated form of the enzyme, which might provide a basis for developing new strategies in the treatment of PD. </li></ul>
  14. 14. Thank you !