Introduction to Enzymology - University of...
Transcript of Introduction to Enzymology - University of...
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Introduction to Enzymology
• Functional Properties
• Nomenclature
• Enzyme specificity
• Enzyme regulation
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Introduction to Enzymology
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Enzymes - Biological catalysts
• By definition a Catalyst :- Accelerates the rate of chemical reactions - Capable of performing multiple reactions (recycled)- Final distribution of reactants and products governed by
equilibrium properties• Enzymes are biological catalysts
- Proteins, (a few RNA exceptions)- Orders of magnitude faster than chemical catalysts- Act under mild conditions (temperature and pressure)- Highly Specific- Tightly Regulated
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Enzymes are critical for every aspect of cellular life
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Enzyme Properties• Vital for chemical reactions to occur in the cell
(the breaking, forming and rearranging of bonds on a substrate (reactant))
• Modified substrate (now a product) often performs a different task
• Consequence:Transformation of energy and matter in the cellCell-cell and intracellular communicationAllows for cellular homeostasis to persist
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Enzyme Nomenclature
• Transferases– Transfer functional groups between molecules
• Oxidoreductases– Transfer electrons (RedOx reactions)
• Hydrolases– Break bonds by adding H2O
• Lyases– Elimination reactions to form double bonds
• Isomerases– Intramolecular rearangements
• Ligases– Join molecules with new bonds
Superfamilies: EC 1.1.3.4
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Enzymes can be classified using a numbering system defined by the Enzyme Commission.
This system consists of a four digit number which classifies based on the type of reaction the enzyme catalyzes
Enzyme Nomenclature
EC 3.2.1.1
Type of general reaction
(eg. hydrolase)
Subclass of enzyme reaction
(eg. glycosidase)
Sub-Subclass of enzyme reaction
(eg. hydrolyze O-glycosyl groups)
Indicates specific enzyme
(eg. alpha Amylase)
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Enzyme Specificity
• The active site of an enzyme dictates specificity- Tend to be specific for one type of chemical group- Substrates have to interact in stereospecific manner (fit)- Substrates have to bind relatively well (affinity)
• H-bonds, electrostatics, hydrophobicity- Substrates have to react
• bonds to be broken or formed have to have proper reactivity• Substances that fit and bind but don’t react are inhibitors
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Stereospecificity of Enzymes
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Enzyme Specificity
• The active site of an enzyme dictates specificity- Tend to be specific for one type of chemical group- Substrates have to interact in stereospecific manner (fit) - Substrates have to bind relatively well (affinity)
• H-bonds, electrostatics, hydrophobicity- Substrates have to react
• bonds to be broken or formed have to have proper reactivity• Substances that fit and bind but don’t react are inhibitors
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Enzyme Active Sites
Lysozyme active site: Green shows substrate contacts and orange are catalytic residues
Active site complements structure of substrate
Contain amino acids that function in substrate binding, chemical catalysis, and product release
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Enzyme Three Dimensional Structure
X-ray crystallography (also NMR); physical methods to solve structure of enzymes
Conformation with or without substrate provides functional/biological information
Used to identify amino acids involved in catalysis
Example: Prostaglandin Synthase I with arachidonic acid
PGHS (COX) target of aspirin
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Enzyme Three Dimensional Structure
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Enzyme Regulation
• Enzymes are tightly regulated light switches• Unregulated enzymes become constitutively
active or inactive (light is always on or off)• Unregulated enzyme activity disrupts cell
homeostasis and often lead to disease states.
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SummaryEnzymes are biological catalysts vital for cellular life
Their activities are carefully orchestrated and highly specific
A multitude of different families of enzymes exist allowing for a diverse array of chemical catalysis to occur in the cell
Next class:Chemical catalysis:
Transition state theory
Hammond’s Postulate
Principles of catalysis