Part II Structure and Catalysis

1. 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 13Biosignaling

2. Chapter 13 Biosignaling

3. Molecular Mechanisms of Signal Transduction

5. Scatchard Plot: Quantifies the Receptor-Ligand Interaction R + L RL

6. Four general types of signal transducers

7. Gated Ion Channels Ion Channels Underlie Electrical Signaling in Excitable Cells Transmembrane electrical potential

8. CH3 O + CH3-N-CH2CH2O-C-CH3 CH3 The Nicotinic Acetylcholine Receptor is a Ligand-Gated Ion Channels

9. 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)

10. Receptor Enzymes Tyrosine- specific protein kinase

11. Regulation of gene expression by insulin

12. Activation of glycogen synthase by insulin

13. 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

14. G protein-Coupled Receptors and Second Messengers (Adrenaline) Serpentine receptors b-adrenergic receptor Gs: Stimulatory G protein (a, b and g subunits)

15. Interaction of Gsa with adenylyl cyclase (AC) AC Gsa Forskolin GTP

16. Self-inactivation of Gs AC

17. Activation of cAMP-dependent protein kinase, PKA ATP PKI a C subunit of PKA

19. Epinephrine Cascade

20. Degradation of cAMP by Cyclic Nucleotide Phosphodiesterase

21. Desensitization of the b-Adrenergic Receptor b-arrestin

22. Two Second Messengers Are Derived from Phosphatidylinositols Gq Phospholipase C (IP3) Diacylglycerol (DG) Protein kinase C (PKC)

24. Calcium Is a Second Messenger in Many Signal Transductions Thymocytes (loaded with fura dye) A single hepatocyte norepinephrine Cytosolic [Ca2+] < 10-7 M

25. Calmodulin (CaM) CaM kinase II peptide

26. 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)

27. Light-induced hyperpolarization of rod cells (Light induces degradation of cGMP)

28. Likely structure of rhodopsin complexed with G protein transducin 11-cis-retinal opsin (rhodopsin) transducin (abc subunits)

29. Molecular consequences of photon absorption by rhodopsin

30. Cone cells specialize in color vision – different opsins Color Blindness red- or green- dichromats

31. Vertebrate Olfaction, and Gustation Use Mechanisms Similar to the Visual System

33. Common features of signaling systems that detects hormones, light, smells, and tetastes

34. Toxins produced by bacteria that cause cholera and whooping cough (pertussis)

35. Regulation of Transcription by Steroid Hormons

36. Antagonist of steroid hormones as drugs Antagonist of progesterone - terminate early pregnancies Antagonist of estrogen - breast cancer treatment

37. Regulation of Cell Cycle by Protein Kinases Eukaryotic cell cycle

38. Cyclin Activation of cyclin-dependent protein kinase (CDKs) by cyclin and phosphorylation T loop (mask active site) Glu51 CDK2 P-Thr ATP

39. Variation in the activities of specific CDKs during the cell cycle in animals

40. Regulation of CDK by phosphorylation and proteolysis DBRP: destruction box recognizing protein

41. Regulation of cell division by growth factors

42. Regulation of passage from G1 to S by phosphorylation of pRb pRb, retinoblastoma protein

43. 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

44. Oncogene-encoded defective EGF receptor Breast, stomach, and ovary cancers

45. From Normal Epithelial Cell to Colorectal Cancer

46. Initial events of apoptosis