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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 Chapter 13 Biosignaling Molecular Mechanisms of Signal Transduction Scatchard Plot: Quantifies the Receptor-Ligand Interaction R + L RL Four general types of signal transducers Gated Ion Channels Ion Channels Underlie Electrical Signaling in Excitable Cells Transmembrane electrical potential The Nicotinic Acetylcholine Receptor is a Ligand-Gated Ion Channels CH3 + O CH3-N-CH2CH2O-C-CH3 CH3 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) Receptor Enzymes Tyrosinespecific protein kinase Regulation of gene expression by insulin Activation of glycogen synthase by insulin 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 G protein-Coupled Receptors and Second Messengers (Adrenaline) Serpentine receptors b-adrenergic receptor Gs: Stimulatory G protein (a, b and g subunits) Interaction of Gsa with adenylyl cyclase (AC) AC Forskolin Gsa GTP Self-inactivation of Gs AC Activation of cAMP-dependent protein kinase, PKA ATP PKI a C subunit of PKA Epinephrine Cascade Degradation of cAMP by Cyclic Nucleotide Phosphodiesterase Desensitization of the b-Adrenergic Receptor b-arrestin Two Second Messengers Are Derived from Phosphatidylinositols Gq Phospholipase C (IP3) Diacylglycerol (DG) Protein kinase C (PKC) Calcium Is a Second Messenger in Many Signal Transductions Thymocytes (loaded with fura dye) A single hepatocyte norepinephrine Cytosolic [Ca2+] < 10-7 M Calmodulin (CaM) CaM kinase II peptide 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) Light-induced hyperpolarization of rod cells (Light induces degradation of cGMP) Likely structure of rhodopsin complexed with G protein transducin 11-cis-retinal opsin (rhodopsin) transducin (abc subunits) Molecular consequences of photon absorption by rhodopsin Cone cells specialize in color vision – different opsins Color Blindness red- or greendichromats Vertebrate Olfaction, and Gustation Use Mechanisms Similar to the Visual System Common features of signaling systems that detects hormones, light, smells, and tetastes Toxins produced by bacteria that cause cholera and whooping cough (pertussis) Regulation of Transcription by Steroid Hormons Antagonist of steroid hormones as drugs Antagonist of estrogen - breast cancer treatment Antagonist of progesterone - terminate early pregnancies Regulation of Cell Cycle by Protein Kinases Eukaryotic cell cycle Activation of cyclin-dependent protein kinase (CDKs) by cyclin and phosphorylation T loop CDK2 Cyclin Glu51 (mask active site) P-Thr ATP Variation in the activities of specific CDKs during the cell cycle in animals Regulation of CDK by phosphorylation and proteolysis DBRP: destruction box recognizing protein Regulation of cell division by growth factors Regulation of passage from G1 to S by phosphorylation of pRb pRb, retinoblastoma protein 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 Oncogene-encoded defective EGF receptor Breast, stomach, and ovary cancers From Normal Epithelial Cell to Colorectal Cancer Initial events of apoptosis