Catalytic Strategies
Serine Proteases
Catalytic Triad
Serine, Histidine, Aspartate
S1 Pocket
Oxyanion Hole
Mechanism
Steps
Inhibition
Serpins / alpha-1-antitrypsin & elastase
Other Proteases
Cysteine proteases, metalloproteases, aspartyl proteases
Carbonic anhydrase
Restriction/ Modification Systems
Allostery & Regulation
Allosterism
ATCase & effectors
Covalent Modification
Zymogens
Proteases
Phosphorylation, acetylation, formylation, acylation, ADP ribosylation,
prenylation, sulfation, ubiquitination, carboxylation
Blood Clotting
Cascading amplification
Cellular Response
Platelets, calcium, von Willebrand factor, thromboxane
Molecular Response
Intrinsic pathway / Extrinsic pathway
Convergence on Factor X
Activation of thrombin in first phase
Amplification phase increases thrombin 1,000,000 fold
Thrombin converts fibrinogen to fibrin
Soft clot / transglutaminase
Carboxylation / vitamin K / Warfari / Ca++
Plasmin / tPA
Carbohydrate Structure
Hexoses / pentoses / tetroses / heptoses / octoses
Monosaccharides
Glucsoe, ribose, galactose, fructose
Aldoses / ketoses
Stereoisomers / enantiomers / epimers / diastereomers / anomers
Cyclization
Fischer vs Haworth
Furanose / Pyranose
Glycosides
Artificial sweeteners
Disaccharides
Sucrose, lactose, maltose
Oligosaccharides
Glycoproteins
Identity
Polysaccharides
Cellulose, glycogen, amylopectin, amylose, chitin
Glycosaminoglycans
N-acetylgalactosamine / N-acetylglucosamine based
Heparin, hyaluronic acid, chondroitin sulfate
Proteoglycans / peptidoglycan
Hyaluronan
Lectins / phytohemagglutinins
Flu / tamiflu
Glycolipids
G-Protein Coupled Receptors
Activation by Hormone Signaling
Epinephrine
Glucagon
Inactivation
Arrestin system
GTPase of alpha subunit
Phosphodiesterase action on cAMP
Inhibits PKA
Inhibited by caffeine
Coffee ‘buzz’
Receptor Tyrosine Kinase (RTKs)
Phosphorylation
Dimerization caused by ligand
Membrane Bound
Autophosphorylation
Signaling Complex
RTK Examples
Insulin Receptor
Always a dimer
IRS-1 & other signaling
Stimulate GLUT 4 movement & glucose uptake
Activates Phosphoprotein phosphatase
Opposes of B-adrenergic pathway
Epidermal Growth Factor (EGF) Receptor
Dimerizes on binding EGF
Stimulates growth, proliferation, differentiation
Ras
Similar to alpha subunit of G-protein
GTPase
Stimulates replication
Effects of mutation
Steroid Hormone Signaling
Effects
Metabolism, Inflammation, Immune system, salt balance, sex
characteristics
Steps in action
Release in blood, crossing lipid bilayer, binding receptor, effects on
transcription
Other Signaling
Nerve transmission
Prostanoids
Signaling Gone Wild
Oncogenes, Proto-oncogenes & Mutations
RAS
GTPase function and effects
Src and control of cell division
HER2
Herceptin
BCR-ABL translocation
Gleevec
Metabolic Energy
Catabolism
Makes ATP, NADH
Anabolism
Uses ATP, NADH
Gibbs Free Energy
∆G = ∆G°’ + RTln({Products}/{Reactants})
Values ∆G and Reaction Direction
∆G°’ and Creatine Kinase
ATP and Potential Energy
Oxidation / Reduction
Energy Coupling
Metabolic Pathways
Roadmaps
Interconnectedness
Central Metabolic Pathways
Glycolysis
Oxygen / Fermentation
Citric Acid Cycle
High Energy Intermediates and Energy Barriers
Glycolysis