Th1L07 Regulation of enzyme activity

Th1L07 Regulation of enzyme activity

1. Allosteric regulation

   • regulation of a protein by binding an effector molecule at a site other than the protein's active site
     • that site is the allosteric site
     • allow effectors to bind to the protein, often resulting in a conformational change involving protein dynamics
   • Sigmoid curve (compared to hyperbolic curve of M-M kinetics)
   • Allosteric activator
     • Opens up active site, making it more open to substrate
       • more or less effective active site
     • Negative allosteric effectors
       • Eg. ATP and citrate on phosphofructokinase (metabolism)
         • ATP can act as positive regulator during glycolysis if there is not enough ATP and citrate
     • Positive allosteric effectors
       • Eg. - "phosphoenolpyruvate (PEP) and fructose 1,6 bis phosphate on pyruvate kinase
         • PFK acts as a positive allosteric regulator of phosphenyolpyruvate to pyruvate (a later step in glycolysis); good example of co-ordinated regulation

2. Pharmacological altering of enzyme activity

3. Covalent modification by other enzymes

   • Most common form is the addition or removal of phosphate from Ser, Thr, Tyr, His residues
     • Dephosphorylation of serine 14
       • by phosphorylase phosphatase
     • Glycogen synthase kinase 3
       • phosphorylates at several serine resides; inactivates the enzyme entirely
   • Glucose metabolism
     • Coordinated regulation of synthesis and breakdown of glycogen via adrenaline and glucagon
     • Shows how protein phosphorylation may be increasing or decreasing activity of even catalysis of a different reaction
   • Phosphorylation (regulation of glucose metabolism)
     • Single cascade system
     • Increases activity of glycogen phosphorylase, which is responsible for degrading glycogen
     • occurs by phosphorylase kinase serine 14 and requires ATP; ALSO reduces activity of glycogen synthase (synthesises glycogen)
   • Other
     • Adenylylation or AMPylation (Tyr residues, ATP to PPi)
     • Uridylylation (Tyr residues, UTP to PPi)"

4. Induction or repression of enzyme synthesis

   • e.g. High blood glucose levels lead to an increase in insulin production
     • Insulin increases rate of synthesis of key enzymes involved in glucose metabolism
       • Glucokinase, phosphofructokinase, pyruvate kinase

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