L5 Regulation of Enzyme Action PDF

Regulation of enzyme action By the end of this lecture, the students should be able to: 1. Summarize enzyme regulation by allosteric regulation. 2. Identify causes of changing enzyme amount and activity. 3. Discuss enzyme: induction, repression and degradation. 4. Explain feedback regulation...

Regulation of enzyme action By the end of this lecture, the students should be able to: 1. Summarize enzyme regulation by allosteric regulation. 2. Identify causes of changing enzyme amount and activity. 3. Discuss enzyme: induction, repression and degradation. 4. Explain feedback regulation, covalent modification and regulation by cleavage Regulation of enzyme action I. Control of enzyme quantity 1. Induction 2. Repression II. Altering the enzyme catalytic efficiency 1. Allosteric regulation 2. Feedback inhibition 3. Covalent modification. 4. Proenzyme (zymogen). 5. Protein-protein interaction. Protein kinases are enzymes that control the activity of other enzymes by adding phosphates groups (phosphorylation). When the enzyme is phosphorylated, it changes its activity (it becomes more or less active, depending on the enzyme). 1. What is the name of the regulatory mechanism in which protein kinase enzyme is involved in? 2. List the other mechanism regulating the catalytic activity of the enzyme. 3. Why regulation of enzyme activity is importance?  Regulation of enzyme activity Regulation of enzyme action Control of enzyme quantity Altering the enzyme catalytic efficiency 5.Protein- 1.Allosteric 2.Feedback 3.Covalent 4.Proenzyme 1.Induction 2.Repression. protein regulation. inhibition. modification (zymogen interaction Control of enzyme quantity 1. Induction 2. Repression  I. Control of enzyme quantity ✓ Change in Enzyme amount (Increase or decrease the amount) ✓ Long term regulation (at the level of gene expression) ✓ Slow (hrs., days) ✓ It work by controlling the rate of Enzyme synthesis by either: Induction or Repression 1- Induction 2- Repression ↑ rate of enzyme synthesis by substances ↓ rate of enzyme synthesis by substances called inducers called repressors Inducers Repressors substances that increase the rate of enzyme substances that decrease the rate of enzyme synthesis at the level of gene expression synthesis at the level of gene expression are usually end products the reaction, so repression is sometimes called feedback regulation. Inducible enzymes: the conc. of these De-repression: removal of the repressor→ enzymes depends on the presence of inducers enzyme synthesis retains its normal rate. Control of enzyme catalytic efficacy 1. Allosteric regulation 2. Feedback inhibition 3. Covalent modification. 4. Proenzyme (zymogen). 5. Protein-protein interaction.  II. Control of enzyme catalytic efficacy ✓ Change in Enzyme activity (by increase or decreasing the activity) ✓ Short term regulation ✓ Rapid (secs, mins) ✓ It work through : 1. Allosteric regulation 2. Feedback inhibition 3. Covalent modification. 4. Proenzyme (zymogen). 5. Protein-protein interaction. 1. Allosteric regulation ✓ Some Enzyme has two sites; 1- Active site for substrate binding and catalysis 2- Allosteric site (another site) for effector (regulator) binding → for regulation of the E activity ✓ Binding of the allosteric effector to the regulatory site → conformational changes in the catalytic site→ becomes either 1. More fit for substrate binding→ ↑ Enz. activity → so called +Ve effector (allosteric activator). 2. Unfit for substrate binding → ↓ Enz. activity → so called -Ve effector (allosteric inhibitor) Effector as an inhibitor Effector as an activator 2. Feedback Inhibition ✓ In biosynthetic pathways, an end product may directly inhibit an enzyme early in the pathway. ✓ This inhibited enzyme usually catalyzes the early functionally irreversible step in the pathway A: Initial reactant B, C : Intermediates D: End (Final) product Accumulation of end product (D)→ back signal (-Ve feedback) → ↓↓ of Enzyme1→ slow the pathway  3. Pro-enzymes (Zymogens) ✓ Some Enz. initially produced in inactive form called zymogen or proenzyme as it contains a polypeptide segment that blocks the active site. ✓ Removal of this polypeptide segment→ activation of zymogen ✓ This activation is an irreversible process ✓ Examples for zymogens include: proteolytic digestive enzyme: that digest protein like: 1. Pepsinogen, 2. Trypsinogen, 3. Chymotrypsinogen, ✓ This inactive form → protect the tissues of origin from auto digestion (ie. from digesting itself). 4- Protein-protein interaction ✓ Some enzymes are, formed of inactive form, consists of catalytic and regulatory subunits. ✓ Activation of the enzyme occurs by separation of the catalytic subunits from the regulatory subunits. ✓ Eg Protein Kinas A (PKA) enzyme : Formed of 4 subunits, 2 regulatory (2R) and 2 catalytic (2C) subunits. The whole enzyme (2R2C) is inactive cAMP activates the enzyme by binding to the 2 regulatory (2R) subunits → releasing the 2 catalytic (2C) (active) subunits. 5- Covalent modification ✓ It means modification of enzyme activity through formation of covalent bonds e.g., Phosphorylation, Acetylation , Methylation ✓ Phosphorylation/ dephosphorylation the most covalent modification used to regulate enzyme activity It involve transfer of phosphate (of ATP) to & from OH group of: Serine ,Threonine or Tyrosine AA of the enzyme. Two enzymes involved For phosphorylation: Protein Kinases → add P For dephosphorylation: Phosphatases → remove P Some enzymes activated by phosphorylation other activated by dephosphorylation Protein kinases are enzymes that control the activity of other enzymes by adding phosphates groups (phosphorylation). When the enzyme is phosphorylated, it changes its activity (it becomes more active or less active, depending on the enzyme). 1. What is the name of the regulatory mechanism in which protein kinase enzyme is involved in? Phosphorylation is the most common type of Covalent modification that regulate the enzyme activity. 2. List the other mechanism regulating the catalytic activity of the enzyme. 3. Why regulation of enzyme activity is importance? ✓ To coordinate the different metabolic processes inside the body ✓ To maintain the internal environment of the body constant ( homeostasis)  REFERENCES ❑ Chatterjea’s Textbook of Medical Biochemistry, 8th edition. ❑ Vasudevan's Textbook of Biochemistry For Medical Students, 6th Edition. ❑ Lippincott’s Illustrated Reviews: Biochemistry, 8th edition ❑ https://www.youtube.com/watch?v=wvTv8TqWC48 ❑ https://www.youtube.com/watch?v=PPJ7C3hcnPw ❑ https://www.vedantu.com/biology/mcqs-on-enzymes