Enzyme regulation

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Enzyme regulation

  1. 1. Enzyme Regulation
  2. 2. REGULATION OF ENZYME ACTIVITY Enzyme quantity – regulation of gene expression (Response time = minutes to hours) a) Transcription b) Translation c) Enzyme turnover
  3. 3. Enzyme activity (rapid response time = fraction of seconds) Allosteric regulation Covalent modification Association-disassociation’ Proteolytic cleavage of proenzyme
  4. 4. ALLOSTERIC REGULATION End products are often inhibitors Allosteric modulators bind to site other than the active site Allosteric enzymes usually have 4 o structure Vo vs [S] plots give sigmoidal curve for at least one substrate Can remove allosteric site without effecting enzymatic action
  5. 5. REGULATION OF ENZYME ACTIVITY (BIOCHEMICAL REGULATION) 1 st committed step of a biosynthetic pathway or enzymes at pathway branch points often regulated by feedback inhibition. 1 A 2 C B X H 4” I 3” 3’X E 4’ F 5” 5’ J G Efficient use of biosynthetic precursors and energy
  6. 6. PHOSPHOFRUCTOKINASE( PFK) Fructose-6-P+ATP ---> Fructose-1,6-bisphosphate + ADP •PFK catalyzes 1st committed step in glycolysis (10 steps total) (Glucose + 2ADP + 2 NAD+ + 2Pi  2pyruvate + 2ATP + 2NADH) •Phosphoenolpyruvate is an allosteric inhibitor of PFK •ADP is an allosteric activator of PFK
  7. 7. ALLOSTERIC MODULATORS BIND TO SITE OTHER THAN THE ACTIVE SITE AND ALLOSTERIC ENZYMES HAVE 4 O STRUCTURE Fructose-6-P + ATP -----> Fructose-1,6-bisphosphate + ADP ADP Allosteric Activator (ADP) binds distal to active site
  8. 8. VO VS [S] PLOTS GIVE SIGMOIDAL CURVE FOR AT LEAST ONE SUBSTRATE Binding of this allosteric inhibitor or this activator does not effect Vmax, but does alter Km Allosteric enzyme do not follow M-M kinetics
  9. 9. ALLOSTERIC T TO R TRANSITION I ET-I I S ET Concerted model ER Sequential model S ER-S
  10. 10. COVALENT MODIFICATION •Regulation by covalent modification is slower than allosteric regulation •Reversible •Require one enzyme for activation and one enzyme for inactivation •Covalent modification freezes enzyme T or R conformation
  11. 11. PHOSPHORYLATION /DEPHOSPHORYLATION •Most common covalent modification • Involve protein kinases/phosphatase •PDK inactivated by phosphorylation •Amino acids with –OH groups are targets for phosphorylation •Phosphates are bulky (-) charged groups which effect conformation
  12. 12. ENZYME REGULATION BY ASSOCIATION/DISASSOCIAT ION Carboxylase •Acetyl-CoA •acetyl-CoA + CO2 + ATP  malonyl-CoA + ADP + Pi •1St committed step in fatty acid biosynthesis •In presence of citrate activated •In presence of fatty acyl-CoA inactivated citrate polymerized unpolymerized Fatty acyl-CoA
  13. 13. PROTEOLYTIC CLEAVAGE OF PROENZYME(ZYMOGEN)
  14. 14. PROINSULIN TO INSULIN
  15. 15. BLOOD CLOTTING •Clotting involves series of zymogen activations •Seven clotting factors are serine proteases involved in clotting cascade rxns
  16. 16. X X X X X X

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