Download
slide1 n.
Skip this Video
Loading SlideShow in 5 Seconds..
Page 639 PowerPoint Presentation

Page 639

106 Vues Download Presentation
Télécharger la présentation

Page 639

- - - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

  1. Figure 18-13 Schematic diagram of the major enzymatic modification/demodification systems involved in the control of glycogen metabolism in muscle. o= original m=modified Page 639

  2. Candace Parchen (BS Cell Molec. Biol. 2004) will give the Biology seminar next Wednesday 2/10 (4pm in BI 234).  Title: The Effect of Phosphodiesterase 5 (PDE5) inhibitors on Dystrophic Hearts Annual T-shirt contest is underway. Strut your geeky stuff!!!!!

  3. Figure 18-14X-ray structure of the catalytic (C) subunit of mouse protein kinase A (PKA). ATP inhibitor Page 641 PKs have KEY roles in signalling 1.7% of human genome = kinases 1000 putative kinase genes!

  4. Figure 18-15 X-ray structure of the regulatory (R) subunit of bovine protein kinase A (PKA). Autoinhibitory domain Fits in active site of C Keeps complex inactive Page 641

  5. Phosphorylase Kinase • Senses Ca+2 • Activated by [Ca+2] as low as 10-7M!! • 4 subunits (αβγδ)4 active structure a tetramer of tetramers! • Subunit γ has catalytic activity • Others are inhibitory • Subunit δ = Calmodulin (CaM)

  6. Figure 18-16 X-Ray structure of rat testis calmodulin. Ca+2 binding induces a conformational change exposing a met-rich hydrophobic region. 4 binding sites for Ca+2 Flexible stalk May be random coil really Page 642 Nerve impulses into muscle trigger Ca+2 release Why would increased [Ca+2 ]promote glucose mobilization?

  7. methionine sulfur atoms key nonpolar areas The non-polar amino acids form two neat grooves (red stars) when calcium binds,. Because these non-polar grooves are generic in shape, calmodulin acts as a versatile regulatory protein and its targets are not required to possess any specific amino acid sequence or structural binding motifs. In phosphorylase kinase, CaM-Ca+2 binds strongly to the γ subunit and increases its activity.

  8. Figure 18-17 EF hand, the calcium binding site. Octahedral geometry for Ca+2 Page 642

  9. Figure 18-18a. NMR structure of (Ca2+)4–CaM from Drosophila melanogaster in complex with its 26-residue target polypeptide from rabbit skeletal muscle myosin light chain kinase (MLCK). (a) A view of the complex in which the N-terminus of the target polypeptide is on the right. Page 643 Target peptide

  10. Figure 18-18b. NMR structure of (Ca2+)4–CaM from Drosophila melanogaster in complex with its 26-residue target polypeptide from rabbit skeletal muscle myosin light chain kinase (MLCK). (b) The perpendicular view as seen from the right side of Part a. Page 643

  11. Figure 18-19 Schematic diagram of the Ca2+–CaM-dependent activation of protein kinases.

  12. Figure 18-21 The antagonistic effects of insulin and epinephrine on glycogen metabolism in muscle. Phosphoprotein phosphatase 2 Mn+2 activate water for nucleophillic attack Page 645

  13. Maintaining steady blood [glc] Figure 18-22 The enzymatic activities of phosphorylase a and glycogen synthase in mouse liver in response to an infusion of glucose. Hi [glc] stimulates insulin secretion Low [glc] stimulates glucagon secretion Page 648

  14. Figure 18-23 Comparison of the relative enzymatic activities of hexokinase and glucokinase over the physiological blood glucose range. NOT inhibited by G6P Page 649

  15. Figure 18-24 Formation and degradation of -D-fructose-2,6-bisphosphate as catalyzed by PFK-2 and FBPase-2. Page 649 These 2 activities are located on 2 different domains of the same protein! PKA is a ser kinase It decreases PFK activity and increases FBPase activity.

  16. Glucoagon Action in Liver vs. Muscle Liver • ↑cAMP • ↑PKA • ↓[F2,6BP] • glycolysis↓ • Muscle • ↑ Glycogen breakdown • ↑glycolysis HUH??? --Different isozymes --Different phosphorylation sites --Different Kinetics!!!

  17. Figure 18-25 X-ray structure of the H256A mutant of rat testis PFK-2/FBPase-2. PFK 2 Page 650 FBPase

  18. Figure 18-26b The liver’s response to stress. (b) The participation of two second messenger systems. Page 652

  19. Figure 18-26a The liver’s response to stress. (a) Stimulation of α-adrenoreceptors by epinephrine activates phospholipase C to hydrolyze PIP2 to IP3 and DAG. Page 652

  20. Fig. 19-16 Receptor-mediated activation/inhibition of Adenylate Cyclase

  21. Figure 19-13 Activation/deactivation cycle for hormonally stimulated AC. Page 674

  22. Figure 19-14 General structure of a G protein-coupled receptor (GPCR). Page 674

  23. Figure 19-51 Role of PIP2 in intracellular signaling. Page 708

  24. Figure 19-21 Schematic diagram of a typical mammalian AC. Page 682

  25. Figure 19-50 Molecular formula of the phosphatidylinositides. Page 707

  26. Figure 19-52 A phospholipase is named according to the bond that it cleaves on a glycerophospholipid. Page 709

  27. Figure 19-57 Activation of PKC. Page 713

  28. Figure 19-64 Insulin signal transduction. Page 719

  29. Figure 18-27 The ADP concentration in human forearm muscles during rest and following exertion in normal individuals and those with McArdle’s disease. (Muscle Phosphorylase Deficiency) Page 653

  30. Table 18-1Hereditary Glycogen Storage Diseases. Page 651

  31. Figure 20.2

  32. For diffusion Keq = 1, thus DG°’ = 0 Start of “reaction” equilibrium

  33. For diffusion Keq = 1, thus DG°’ = 0

  34. Figure 20.3

  35. “non-mediated” transport

  36. Table 20-1

  37. Figure 20.4

  38. Figure 20-9Valinomycin(K+ complex)

  39. Figure 20-9Monensin(Na+ complex)

  40. a-hemolysin (Staph. aureus) “IONOPHORES” Gramicidin A See Figure 20.11

  41. Figure 20.14

  42. Figure 20.15

  43. Figure 20.18

  44. Table 20-3

  45. Figure 20.21