10 8 12 Lecture 15 GLUT transporters 1 2 3 4 Vast majority of tissues used 1 and 3 GLUT 2 liver and pancreas Higher range of operation Km 15 25 mM functions over wider range Reflects function of tissue Liver high level glucose liver will pick up glucose and store as glycogen Pancreas responds to elevated glucose levels to release insulin Glucose Transport induced by insulin Muscle and fat cells availability of insulin triggers sequence of transport molecules inserted into cells to pick up glucose from blood till blood glucose levels drop Saltiel Kahn 2001 made GLUT 4 fluorescent Fluoresced around plasma membrane where internal compartments resided once insulin was added Once insulin removed fluorescence lost Regulation of Facilitated Diffusion movement of water across kidney cells tubules Humans 10 different types of aquaporins Each coded by a specific gene Different forms of channels in different tissues And each plays a different role Structures remain similar Aquaporin 6 membrane spanning domains alpha helices in green form wall of cylinder Core provides channel 2 helices 1 hanging from top and 1 from bottom Selectivity loops depending on amino acid groups alter selectivity Aquaporin 1 in human RBC B E selectivity loops Depict specific amino acids Determine what can and cannot pass through aquaporin Molecular weight 28 000 D Aquaporins typically found as tetramers 4 channels form complex Chain of sugars attached to extracellular domain Aquaporin 7 found in fat cells adipocytes 2 copies of gene that code for aquaporin are found 1 from mother and father when mutation in this gene found mice found to become obese knock out mice method while adipocytes synthesize lipids they are maintained as droplets lipid droplets While they are normally broken down to make energy The Lipids are triglycerides glycerol fatty acids Oxidation of these molecules involve separation of glycerol from fatty acids Each becomes liberated from each other and are oxidized Where aquaporin 7 is defected the glycerol that has been liberated is unable to exit the cell Shifting the equilibrium toward glycerol synthesis instead of glycerol break down Increases activation of the enzyme glycerol kinase Now more inclined to synthesize more glycerol than break them down Kidneys receive blood from aorta to renal artery Goes through process where CO2 is removed urea As blood goes through kidney tubules sometimes salts proteins are squeezed out of blood products fluid is drained through ureter Stored in urinary bladder and finally released How does volume of excreted fluid regulate movement of water Nephron blood vessels form thin capillary over top of water sodium glucose some proteins get squeezed inside capsule and out of the blood vessels Liquid goes down tubules and eventually makes it to bladder Some filtrates may be retrieved through movement down tubules Wall of tubule cylinder of cells Well hydrated large volume of urine released compared to when dehydrated high levels of electrolytes How body retains water in these times If water is to be retained and volume of water is to be decreaed in urine water is allowed to be flowed through cell and be picked up by blood More aquaporin 2 is sent to membrane Water flows through Aquaporin 2 facing collecting duct Aquaporin 3 4 to exit cell and be picked up by blood If well hydrated volume of urine is going to be high Dehydrated urine volume decreases Increase water uptake from urine More aquaporin 2 channels will be found Anti Diuretic Vasopressin increases blood pressure by decreasing urine output 9 amino acid peptide secreted from pituitary gland Osmo sensors provide signal to brain How does neuron sense levels of water If dilute cells will swell If concentrated with electroylytes cell will shrink slightly Will stimulate cells in pituitary to secrete vasopressin What makes osmo sensors fire 1 Vasopressin is secreted because organism is to retain fluid 2 Vasopressin Signal will bind to receptor of cell 3 Signals to activate PKA protein kinase A Protein ATP phosphorylated protein ADP 4 Process of phosphorylated proteins these proteins are on surface of vesicles of aquaporin 2 These vesicles will deliver aquaporin 2 s to membrane 5 Amount of fluid going to urine is now reduced When Aquaporin 2 is Defected Consistent high levels of urine Ions consistently lost Diabetis Insipidus 2 possibilites Central Nephrogenic Central problem in brain Osmo senor responsible for triggering ADH does not function Or hormone itself is not functional Nephrogenic aquaporin 2 may not be functioning Or receptor is not functioning These are inherited OR high doses of lithium damage kidney and affect urine output Chapter 3 kinetic curves REVIEW Michaelis Menton Equation S glycerol concentration If glycine diminishes movement glycerol into cell we can agree that glycine uses same channel as glycerol MEMORIZE EQUATION If glycine is added and creates shift in glycerol curve V max is same but Km is higher
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