CELL SIGNALLING and MEMBRANE TRANSPORT. Mark Louie D. Lopez Department of Biology College of Science Polytechnic University of the Philippines
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1 CELL SIGNALLING and MEMBRANE TRANSPORT Mark Louie D. Lopez Department of Biology College of Science Polytechnic University of the Philippines
2 GENERIC SIGNALLING PATHWAY
3 CELL RESPONSE TO SIGNALS
4 CELL RESPONSE TO SIGNALS
5 IMPORTANT CHARACTERS IN PATHWAYS Messengers Kinase Ligand Receptors Signal Transduction Pathway
6
7
8
9
10 TRANSCRIPTION FACTORS Assist in initiating eukaryotic transcription Enhancers Promoter Gene DNA Transcription factors Activator proteins Other proteins RNA polymerase Bending of DNA Transcription
11 Nucleus Master control gene myod Other muscle-specific genes Embryonic precursor cell DNA OFF OFF
12 Nucleus Master control gene myod Other muscle-specific genes Embryonic precursor cell DNA OFF OFF 1 Myoblast (determined) Determination. Signals from other cells lead to activation of a master regulatory gene called myod, and the cell makes MyoD protein, a transcription factor. The cell, now called a myoblast, is irreversibly committed to becoming a skeletal muscle cell. mrna MyoD protein (transcription factor) OFF
13 Nucleus Master control gene myod Other muscle-specific genes DNA Embryonic precursor cell OFF OFF 1 Myoblast (determined) Determination. Signals from other cells lead to activation of a master regulatory gene called myod, and the cell makes MyoD protein, a transcription factor. The cell, now called a myoblast, is irreversibly committed to becoming a skeletal muscle cell. mrna MyoD protein (transcription factor) OFF 2 Differentiation. MyoD protein stimulates the myod gene further, and activates genes encoding other muscle-specific transcription factors, which in turn activate genes for muscle proteins. MyoD also turns on genes that block the cell cycle, thus stopping cell division. The nondividing myoblasts fuse to become mature multinucleate muscle cells, also called muscle fibers. mrna mrna mrna mrna Muscle cell (fully differentiated) MyoD Another transcription factor Myosin, other muscle proteins, and cell-cycle blocking proteins
14 PATTERNS OF CELL COMMUNICATION Autocrine Paracrine Encdocrine Neuroendocrine
15 AUTOCRINE
16 PARACRINE
17 ENDOCRINE
18 NEUROENDOCRINE
19 NEED TO TRANSPORT Cells maintain high K+ and low Na+ ICF K+ - rich ECF Na+, Cl- - rich Plasma & interstitial similar solute composition but no plasma proteins from the interstitium
20 GRADIENT Difference in concentration of substance on one to to another Chemical Gradient Electrical Gradient
21 Electric Potential Electrochemical gradient Chemical Concentration
22 GRADIENT
23 GIBB-DONNAN S EQUILIBRUIM refers to the uneven distribution of charged particles on one side of a semipermeable membrane. these particles are not able to evenly distribute themselves by diffusion across both sides of the membrane.
24 DONNAN S EQUILIBRUIM
25 DONNAN S EQUILIBRUIM
26 MEMBRANE ELECTRIC POTENTIAL Electrochemical equilibrium The state at which the concentration gradient of an ion across a membrane is precisely balanced by the electric potential across the membrane. Electrochemical potential The electrical potential developed across a membrane due to a chemical concentration gradient of an ion that can diffuse across the membrane.
27 NERNST EQUATION The Nernst equation gives a formula that relates the numerical values of the concentration gradient to the electric gradient that balances it.
28 NERNST EQUATION R= gas constant/ gas constant, which is 8.31 (voltcoulomb)/(mol-k) T= absolute temperature F= faraday s constant/ coulombs/mol
29 NERNST EQUATION EXAMPLE
30 NERNST EQUATION EXAMPLE
31 TYPES OF TRANSPORTATION Passive Transport allow water soluble substances (small polar molecules and ions) to pass through the membrane without any energy cost Active Transport The cell expends energy to transport water soluble substances against their concentration gradient
32 PASSIVE TRANSPORT Solute moves down its electrochemical gradient
33 PASSIVE TRANSPORT Requirements Membrane should be permeable Driving force electrochemical gradient or electrochemical potential energy difference Concentration gradient of solute Chemical potential energy difference Difference in voltage
34 PASSIVE TRANSPORT Fick s Law of Diffusion describes diffusion and can be used to solve for the diffusion coefficient
35 FICK S LAW
36 OSMOSIS Process of net movement of water caused by a concentration difference From a higher to a lower water concentration
37 OSMOTIC PRESSURE
38 OSMOTIC PRESSURE
39 OSMOTIC PRESSURE
40 OSMOLALITY Osmolality Concentration of a solution in terms of the number of particles
41 OSMOLALITY COMPUTATION
42 TONICITY
43 TONICITY Hemolysis Crenation
44 PASSIVE TRANSPORT Substances cross membrane thru Intrinsic membrane proteins Pores Channels Carriers
45 PORES Always open Non-gated channel Can allow molecules <45kDa Examples Porins Perforin NPC Aquaporin
46 PORES Dalton is the unit for atomic mass
47 PORES
48 CHANNELS Alternately open and close With movable barrier or gate Gated pore Undergo conformational transition between open and closed states
49 CHANNELS
50 CARRIERS Facilitated passive diffusion of small solutes (eg. Glucose) Mediate only downhill or passive transport Do not hydrolyze ATP or couple to ETC Each carrier protein has specific affinity for binding solutes Fixed number of carriers to transport X
51 CARRIERS
52 PASSIVE TRASPORT
53 ACTIVE TRANSPORT Process that can transfer a solute uphill across a membrane, against its electrochemical gradient Primary active transport (Direct) Secondary active transport (Indirect)
54 ACTIVE TRASPORT
55 PRIMARY ACTIVE TRASPORT Direct active transport Driving force needed for the net transfer of solute comes from the energy change associated with ATP hydrolysis Example: Na-K pump
56 Na-K PUMP In plasma membrane Each cycle: extrusion of 3Na+ and uptake of 2K+ with 1 ATP
57 Na-K PUMP
58 SECONDARY ACTIVE TRANSPORT Indirect active transport Co-transporter or Symport Exchanger or Antiport Driving force is provided by coupling the uphill movement of one solute to the downhill movement of another solute for which a favorable electrochemical gradient exists
59 CO-TRANSPORTER Symports Generally driven by energy of inward directed Na gradient Driven solute moves in the same direction as the driving solute
60 CO-TRANSPORTER
61 EXCHANGER Antiporters Driven solute moves in opposite direction of the driving solute Exchange cations for cations, anions for anions
62 BULK FLOW
63 ENDOCYTOSIS Process of ingestion of substances by the cell membrane Requires energy supplied by ATP Requires Ca++ Lysosomes Hydrolases Digestive vesicle
64 PINOCYTOSIS Ingestion of small globules of extracellular fluid Occurs continuously Pinocytic vesicle nm The only means by which most large macromolecules esp proteins can enter cell
65 PINOCYTOSIS
66 PINOCYTOSIS
67 PHAGOCYTOSIS Ingestion of large particles (bacteria, cells, degenerating tissue) Only certain cells have this capability Tissue macrophages Some WBC s Initiated when a particle binds with the receptors on the surface of the phagocyte
68 PHAGOCYTOSIS
69 PHAGOCYTOSIS
70 EXOCYTOSIS Process of excretion of undigestible substances by the cell membrane Opposite of endocytosis Example Release of neurotransmitters from the presynaptic nerve endings Release of pancreatic enzyme from acinar cells of pancreas
71 EXOCYTOSIS
72 EXOCYTOSIS
73 2 nd review Review Present a summary of the original article regarding the fluid-mosaic model of cell membrane Limit your presentation to 10 slides. The slide must include important aspect of the paper
74
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