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Part II Structure and Catalysis
5 Amino Acids, Peptides, and Proteins 6 The Three-Dimensional Structure of Proteins 7 Protein Function 8 Enzymes 9 Carbohydrates and Glycobiology 10 Nucleotides and Nucleic Acids 11 Lipids 12 Biological Membranes and Transport 13 Biosignaling
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Chapter 13 Biosignaling
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Molecular Mechanisms of Signal Transduction
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Scatchard Plot: Quantifies the Receptor-Ligand Interaction
R + L RL
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Four general types of signal transducers
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Gated Ion Channels Ion Channels Underlie Electrical Signaling in
Excitable Cells Transmembrane electrical potential
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The Nicotinic Acetylcholine Receptor is a Ligand-Gated Ion Channels
CH3-N-CH2CH2O-C-CH3 CH3 O +
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Voltage-Gated Ion Channels
Produce Neuronal Action Potential Neurons Have Receptor Channels That Respond to A Variety of Neurotransmitters Glycine, glutamate, serotonin, g-aminobutyric acid (GABA)
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Receptor Enzymes Tyrosine- specific protein kinase
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Regulation of gene expression by insulin
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Activation of glycogen synthase by insulin
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Guanylyl Cyclase is a Receptor Enzyme that Generates
The Second Messenger cGMP (diarrhea) cGMP-dependent protein kinase PKG Atrial Natriuretic Factor Heart ANF Kidney ANF/ANFR cGMP Na+/H2O out
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G protein-Coupled Receptors and Second Messengers
(Adrenaline) Serpentine receptors b-adrenergic receptor Gs: Stimulatory G protein (a, b and g subunits)
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Interaction of Gsa with adenylyl cyclase (AC)
Forskolin GTP
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Self-inactivation of Gs
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Activation of cAMP-dependent protein kinase, PKA
ATP PKI a C subunit of PKA
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Epinephrine Cascade
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Degradation of cAMP by Cyclic Nucleotide Phosphodiesterase
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Desensitization of the b-Adrenergic Receptor
b-arrestin
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Two Second Messengers Are Derived from Phosphatidylinositols
Gq Phospholipase C (IP3) Diacylglycerol (DG) Protein kinase C (PKC)
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Calcium Is a Second Messenger in Many Signal Transductions
Thymocytes (loaded with fura dye) A single hepatocyte norepinephrine Cytosolic [Ca2+] < 10-7 M
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Calmodulin (CaM) CaM kinase II peptide
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Sensory Transduction in Vision, Olfaction, and Gustation
Light reception in the vertebrate eye (low levels of light) (colors) inner outer segment (visual cortex of the brain)
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Light-induced hyperpolarization of rod cells
(Light induces degradation of cGMP)
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Likely structure of rhodopsin complexed with G protein transducin
11-cis-retinal opsin (rhodopsin) transducin (abc subunits)
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Molecular consequences of photon absorption by rhodopsin
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Cone cells specialize in color vision – different opsins
Blindness red- or green- dichromats
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Vertebrate Olfaction, and Gustation Use Mechanisms
Similar to the Visual System
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Common features of signaling systems that detects
hormones, light, smells, and tetastes
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Toxins produced by bacteria that cause cholera and
whooping cough (pertussis)
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Regulation of Transcription by Steroid Hormons
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Antagonist of steroid hormones as drugs
Antagonist of estrogen - breast cancer treatment Antagonist of progesterone - terminate early pregnancies
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Regulation of Cell Cycle by Protein Kinases
Eukaryotic cell cycle
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Activation of cyclin-dependent protein kinase (CDKs) by cyclin
and phosphorylation T loop (mask active site) Glu51 CDK2 P-Thr ATP
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Variation in the activities of specific CDKs
during the cell cycle in animals
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Regulation of CDK by phosphorylation and proteolysis
DBRP: destruction box recognizing protein
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Regulation of cell division by growth factors
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Regulation of passage from G1 to S by phosphorylation of pRb
pRb, retinoblastoma protein
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Oncogenes, Tumor Suppressor Genes, and Programmed Cell Death
Oncogenes are mutant forms of the genes for protein that regulate the cell cycle Conversion of a regulatory gene into a viral oncogene
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Oncogene-encoded defective EGF receptor
Breast, stomach, and ovary cancers
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From Normal Epithelial Cell to Colorectal Cancer
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Initial events of apoptosis
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