Regulatory Strategies for Enzymes

1
Lecture 13

• Regulatory Strategies for Enzymes

2
Feedback Inhibition
Product acts as an inhibitor of initial enzymatic
reaction.
Ile inhibits threonine dehydratase.
3
Sigmoidal Kinetics

• Often regulated enzymes with multiple subunits

4
Allosteric enzymes
5
Phosphofructokinase

• Allosterically inhibited by
• ATP
• Citrate
• PEP
• Allosterically stimulated by
• Fructose 2,6 bisphosphate
• AMP, ADP

6
Regulation by Covalent Modification

• Phosphorylation
• Tyr, Ser, Thr, His

7
Regulation by Reversible Covalent Modification

• Adenylylation
• Tyr

O
Adenine
O
Enz
P
ATP
O
O
Enz
OH
OH
8
Glycogen Phosphorylase
9
Glycogen Phosphorylase

• Regulatory cascade
• Hormonal signal
• Allosteric regulation
• Glucose and ATP are inhibitors
• AMP is activator

10
ZymogensRegulation by Proteolytic Cleavage

• Trypsinogen, chymotrypsinogen, and
  procarboxypeptidase are synthesized in pancreas
• Activated in intestine by trypsin
• Trypsin inhibited by pancreatic trypsin inhibitor

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Activation of Chymotrypsin

• In the intestine

12
Activation of Chymotrypsin
13
Another way to regulate enzymatic reactions
Regulate the production of the enzyme. Controlled
at the level of transcription or translation
Modification of mRNA
Protein
DNA
RNA
(positive or negative regulation) Controlled by
transcription factors.