Chapter 9 Enzyme Specificity and Regulation Metabolie regulation is achteved throgh an exguisitely balonced interplay among enzymes
9
9.1.Specificity Is the Result of Molecular Recognition "Induced Fit"and the Transition- State Intermediate
9.1 • Specificity Is the Result of Molecular Recognition “Induced Fit” and the TransitionState Intermediate
Active ste (a)Lock-and-key mocel Active site Transition state conformation (b)nduced俄moce
Substrate Active Key and lock site b ES complex Enzyme Substrate Induce fit ES complex Enzyme
Key and lock Induce fit
The induced conformational change in hexokinase M11.8 D-glucose (a)Before glucose binding (b)After glucose binding Induced fit is the main model for changes in the enzyme to fit the transition state and to bring functional side groups of the enzyme to the right location to help the catalysis
The induced conformational change in hexokinase M11.8 Induced fit is the main model for changes in the enzyme to fit the transition state and to bring functional side groups of the enzyme to the right location to help the catalysis
8.2.Controls Over Enzymatic Activity- General Considerations
8.2 • Controls Over Enzymatic Activity— General Considerations
Regulatory strategies .Product accumulates (The enzymatic rate"slows down"as product accumulates and equilibrium is approached); .Substrates and cofactors(The availability of substrates and cofactors will determine the enzymatic reaction rate); .Allosteric control (aspartate transcarbamoylase, hemoglobin); Multiple forms of enzymes (lactate dehydrogenase); Reversible covalent modification (e.g. phosphorylation/dephosphorylation,protein kinase A);
Regulatory strategies •Product accumulates (The enzymatic rate “slows down” as product accumulates and equilibrium is approached); •Substrates and cofactors (The availability of substrates and cofactors will determine the enzymatic reaction rate); •Allosteric control (aspartate transcarbamoylase, hemoglobin); • Multiple forms of enzymes (lactate dehydrogenase); • Reversible covalent modification (e.g. phosphorylation/dephosphorylation, protein kinase A);
Proteolytic activation(proteases involved in digestion,blood clotting). Regulation at protein level often allows a faster response to changes in cellular conditions (substrate concentrations,hormone action,etc.) than regulation of gene expression. Changes of 3D-structures of proteins are pivotal in many mechanisms of regulation at protein level. Changes in structure regulate binding of substrates(e.g.formation of active sites in enzymes)or interactions with other proteins (e.g. covalent modifications like phosphorylation in signal transduction)
• Proteolytic activation (proteases involved in digestion, blood clotting). • Regulation at protein level often allows a faster response to changes in cellular conditions (substrate concentrations, hormone action, etc.) than regulation of gene expression. • Changes of 3D-structures of proteins are pivotal in many mechanisms of regulation at protein level. Changes in structure regulate binding of substrates (e.g. formation of active sites in enzymes) or interactions with other proteins (e.g. covalent modifications like phosphorylation in signal transduction)
Specialized controls:Enzyme regulation is an important matter to cells,and evolution has provided a variety of additional options, including zymogens,isozymes,and modulator proteins
Specialized controls: Enzyme regulation is an important matter to cells, and evolution has provided a variety of additional options, including zymogens, isozymes, and modulator proteins
zymogens Most proteins become fully active as their synthesis is completed and they spontaneously fold into their native,three- dimensional conformations.Some proteins, however,are synthesized as inactive precursors,called zymogens or proenzymes,that only acquire full activity upon specific proteolytic cleavage of one or several of their peptide bonds
zymogens Most proteins become fully active as their synthesis is completed and they spontaneously fold into their native, threedimensional conformations. Some proteins, however, are synthesized as inactive precursors, called zymogens or proenzymes, that only acquire full activity upon specific proteolytic cleavage of one or several of their peptide bonds