10/8/12Lecture 15GLUT transporters: 1,2,3,4Vast majority of tissues used 1 and 3GLUT 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 insulinGlucose 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/tubulesHumans: 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 loopsdepending on amino acid groups alter selectivityAquaporin-1 : in human RBCB & E: selectivity loops. Depict specific amino acids. Determine what can and cannot pass through aquaporin. Molecular weight: 28,000 DAquaporins typically found as tetramers. 4 channels form complex. Chain of sugars attached to extracellular domain.Aquaporin 7: found in fat cells/adipocytes2 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” methodwhile adipocytes synthesize lipids, they are maintained as droplets. (lipid droplets). Whilethey 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, someproteins, 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 ofelectrolytes.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 tobe 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 brainHow 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 membrane5) 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 EquationS – glycerol concentration.If glycine diminishes movement glycerol into cell, we can agree that glycine uses same channel as glycerol.MEMORIZE EQUATIONIf glycine is added and creates shift in glycerol curve, V max is same, but Km is
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