Download Lecture 12: Enzyme Catalysis Topics: Catalytic Strategies Steps in a

Lecture 12: Enzyme Catalysis
Topics:
Catalytic Strategies
Steps in a Reaction
Summary:
The chemical reactions catalyzed by most enzymes can be classified into one of 6 general types
of reactions.
A few catalytic strategies are used by most enzymes regardless of the particular chemistry they
perform.
Enzyme-catalyzed reactions proceed in an organized series of steps each of which can be
considered separately.
Key Concepts:
Covalent catalysis
Nucleophile
Acid-Base Catalysis
Metal-ion Catalysis
Catalysis by Approximation
Electrostatic Effects, Desolvation, Induced Fit
Displacement reactions
Lecture 13:Mechanism of Chymotrypsin
Topics:
Chemical Mechanism of Chymotrypsin
Summary:
Chymotrypsin is a protease and its activity is regulated by controlled cleavage of its backbone.
Its chemical mechanism proceeds in two stages:
1. Nucleophilic attack on substrate by Ser 195 to form acyl-enzyme complex followed by
2. Deacylation though nucleophilic attack by water on the acyl intermediate.
Key Concepts:
Meaning of burst phase and labelling of Serine 195
Catalytic triad: Roles of His 57, Asp 102, and Ser 195 in mechanism
Occurrences of acid-base catalysis and covalent catalysis in mechanism
Lecture 14: Regulation of Proteins 1: Allosteric Control of ATCase
Topics:
Overview of Regulatory Mechanisms
Description of ATCase
Allosteric Properties of ATCase
Summary:
Aspartate transcarbamoylase (ATCase) is an allosteric enzyme which carries out the first step in
the synthesis of pyrimidine nucleotides.
Allosteric enzymes use changes in conformation to switch between different states which have
different levels of activity.
Binding of allosteric effectors can control the switch between states, and thereby increase or
decrease the enzyme activity to exert control over biological processes.
Key Concepts:
Types of Regulation
Feedback inhibition
Allosteric transition in ATCase
ATP and CTP as allosteric effectors of ATCase
Lecture 15: Regulation of Proteins 2: Allosteric Control of Hemoglobin
Topics:
Hemoglobin and Myoglobin
Allosteric Transition in Hemoglobin
Physiological Role of Hemoglobin
Summary:
Hemoglobin is an oxygen transport protein that carries oxygen from the lungs, where oxygen
levels are high, to tissues where it is needed.
Hemoglobin exhibits cooperative binding of oxygen which is the result of a conformational
switch between a low-affinity state and a high-affinity state.
The affinity of hemoglobin for oxygen can be regulated by allosteric effectors to improve its
physiological performance.
Key Concepts:
Function of hemoglobin
Conformational changes due to oxygen binding
Cooperativity
Role of BPG
Role of Bohr Effect
Lecture 16: Regulation of Proteins 3: Isozymes and Covalent Modification
Topics:
Isozymes
Covalent Modification
Protein Kinase A
Summary:
Isozymes are enzymes which have the same activity but different kinetics or regulatory
properties- differential expression of isozymes allows control over enzyme activity.
Many proteins are regulated by covalent modification. The most common such modification is
phosphorylation.
Protein kinase A carries out phosphorylation of a wide variety of targets in response to cyclic
AMP.
Key Concepts:
Isozymes of LDH
Regulation of histones by acetylation
Kinases and Phosphatases
Role of Protein Kinase A
Lecture 17: Regulation of Proteins 4: Proteolytic Activation
Topics:
Examples
Activation of Digestive Enzymes
Blood Clotting
Summary:
Zymogens are inactive protein precursors which must be converted to their active forms by
specific proteolytic cleavage events.
A variety of digestive enzymes are synthesized as zymogens in the pancreas. They are activated
by proteolysis, and further control of their activities is achieved through the action of specific
inhibitor proteins.
A cascade of zymogen activations resulting in the controlled creation of fibrin aggregates is the
molecular basis of blood clotting.
Key Concepts:
Zymogens
Control of activation
Roles of inhibitor proteins (Serpins)
Emphysema
Activation Cascades
Mechanism of blood clotting
Hemophilia
Lecture 18: Introduction to Membranes
Topics:
Lipid Structure
Properties of Lipid Bilayers
Summary:
Biological membranes are composed of lipids and proteins and form the boundary of the cell and
its compartments.
Phospholipids and glycolipids are formed of fatty acids esterified to a platform (backbone)
molecule and contain other groups such as alcohols or sugars.
Lipids spontaneously assemble into bilayers which are largely impermeable to charged and polar
molecules and which form closed compartments.
Key Concepts:
Fatty acids
Phospholipids
Glycolipids
Cholesterol Micelles
Bilayers
Vesicles
Permeability of bilayers
Lecture 19: Membrane Proteins
Topics:
Architecture of Membrane Proteins
Fluid Mosaic Model
Protein Targeting
Summary:
Different membranes have different protein contents which confer their different capabilities.
Membrane proteins associate with lipid bilayers in a variety of ways. In some cases the amino
acid sequence can suggest structural features in such proteins.
Proteins have internal sequence codes for the organelle to which they should be targeted.
Key Concepts:
Peripheral and Integral membrane proteins
Architecture of membrane proteins
Hydropathy plots
Fluid mosaic model
Targeting sequences
Lecture 20: Membrane Transport
Topics:
Energetics of Transmembrane Transport
Active Transport
Passive Transport
Summary:
Transmembrane concentration differences are not at equilibrium and therefore are a source of
energy which can be used for other purposes.
Two categories of active transporters are pumps, which use the energy of ATP hydrolysis to
transport molecules across membranes, and secondary transporters, which use the energy stored
in a transmembrane concentration gradient.
Passive transporters facilitate diffusion of molecules through membranes and allow equilibrium
to be more rapidly established. Ion channels are examples of passive transporters and play
important roles in nerve cell function.
Key Concepts:
Thermodynamics of transport
Active Transport
Primary transporters (pumps)
Secondary transporters (antiporters, symporters)
Passive transport
Ion channels
Ligand-gated and Voltage-gated ion channels