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Enzymes Lec-IV (1).pdf

  1. ENZYMES REGULATION A B C D Product • One enzyme regulates the rate of overall metabolic sequence as per the cell demands. • Such regulatory enzymes are capable of increasing or decreasing their catalytic activity in response to certain signals. • Usually the first enzyme of the sequence is the regulatory enzyme. • Four major classes of enzymes: - Allosteric or noncovalently regulated - Covalently regulated - Regulation by induction and repression of enzyme synthesis. - Regulation by proteolytic cleavage
  2. Allosteric Enzymes • Allosteric enzymes have one or more allosteric sites • Allosteric sites are binding sites distinct from an enzyme’s active site or substrate-binding site • Molecules that bind to allosteric sites are called effectors or modulators • Binding to allosteric sites alters the activity of the enzyme. This is called cooperative binding. • Effectors may be positive or negative • Effectors may be homotropic or heterotropic • Regulatory enzymes of metabolic pathways are allosteric enzymes (eg: feedback inhibition)
  3. Allosteric Enzymes  Allosteric enzymes tend to be multi-sub unit proteins.  The reversible binding of an allosteric modulator (here a positive modulator M) affects the substrate binding site.
  4. Allosteric regulation
  5. Feedback allosteric inhibition Glycine + Succinyl-CoA δ- Aminolevulenic acid synthase δ- Aminolevulenic acid A B Haem Homotropic effectors: Substrate itself acts as an effector Heterotopic effectors : Metabolites other than substrate acts as modulator
  6. covalent modifications
  7. Covalently regulated enzymes Phosphorylation or Dephosphorylation from specific serine, threonine or tyrosine residues of enzyme . Protein OH Ser Thr Tyr (His) Kinase phosphorylation Dephosphorylation Phosphatase Conformational Change P Glycogen phosphorylase b Glycogen phosphorylase a Inactive Active
  8. Enzymes regulated by induction and repression of Enzyme Synthesis • Induction and repression leads to alteration in the total population of active sites. Enzymes regulated by specific proteolytic cleavage Pepsinogen Pepsin Chymotripsinogen Chymotrypsin Trypsinogen Trypsin Procarboxypeptidases Carboxypeptidases Proelastase Elastase Cascade regulatory mechanism Blood Coagulation