BIOL 319 1st EditionFinal Exam Study GuideEXAM 4 REVIEW NOTES AND STUDY GUIDETest 4-TOXINS, INHIBITORS AND POISONSProtein that binds nicotine- nicotinic receptorRealized that body makes endogenous ligand- acetylcholine receptor!- binds nicotineAcetylcholine gated ion channels in brain linked to addictive behavior- affects at much lower dosesAcetylcholine gated ion channel agonist- nicotine can act just like acetylcholine on skeletal muscle cell- would need in huge amounts, mimic of endogenous ligandAntagonist- a chemical that binds a receptor but sits in key hole and doesn’t open up gate- inhibitor, acetylcholine blocker, can out compete endogenous acetylcholine that is released and block it from binding, but does not activate anything itself, “blockers”Ach curare blocker- if gets into blood stream and extracellular fluid; it can get into synapses in high concentrations and block activity of acetylcholine once released - discovered by Indians, found in plant, gets into animals circulatory system and causes paralysis, inhibits acetylcholine puff, animal has muscle weakness and collapses, ingesting it is not toxic because it gets broken up in GI tractanesthesiology- creates relaxation in muscles, makes them unconscious, shuts down CNS but not too much- go into deep sleep, then use something to relax muscles at neuromuscular junction but not interfere with CNSSHOW ME A TOXIN AND I’LL SHOW YOU A MEDICINE Botulinum- too much would cause paralysis, but at the right amount can be helpfulToxins- water can be a toxin! 11/13Can help in small amounts, hurt in large onesPer kg/body weight is normalized for all people dependent upon body weightAntagonist- competitor- acetylcholine and curare compete for binding site- antagonist binds and does nothing to open up channel, but locks others from bindingCurare paralyzes, but does not mess with CNSBotulinum Toxin Mechanism-Bacteria- spores that do not need oxygen to be active, thrives in no oxygen, protein toxin considered to be most toxic substance on earth per kilogram body weight for humans, botulism poisoningSnare proteins and matching proteins on vesicle- brings it against membrane and can exocytose when Calcium is thereProtein can get into blood and becomes toxic by binding to receptor in transmembrane protein at axon terminal, is then brought into cell- receptor mediated endocytosis, fakes out cell because so close to shape on binding site- “Trojan horse”When toxic comes in, hydrolyzes snare proteins and makes them inactive, so they cannot exocytose or interact with membrane- releasing any acetylcholineMuscle sits paralyzed- starts in head and spreads throughout bodyBotox- spinal cord motor neurons affected during stroke and cannot be inhibited by brain, so people spasm, botox relieves spasm, Acetylcholinesterase inhibitor- nerve gas (serin) used in acts of terror, fluorinated organic phosphate, causes immediate convolsions when taken up respiratory route, causes death, nerve gas inhibits acetylcholinesterase and overstimulates- makes person go into convulsions, irreversibly binds acetylcholinesteraseThe good: organophosphates are pesticide used to control insects, very toxic to them but not as much to humans Inhibits acetylcholinesterase MILDLY- can treat people with autoimmune disease whereperson making antibodies to acetylcholine gated ion channels in synapse- inhibit function of synapse, antibodies binding and not allowing acetylcholine to bind, pulling channels into cell and removing them from cell surface- muscle weakness, can inhibit a little in the synapse to boost Ach and outcompete antibody which is causing problemMuscle Metabolism- has capacity to make ATP fast when it needs it, does not store it butstores the oxygen it needs for itMuscle energy supply- get energy from 1. glucose, glycogen is polymerized glucose which can be rapidly broken down, 2. Fat when glucose is running out- muscles eat fatty acids up form the blood when it is released during exerciseGLUCOSE: glycolysis takes glycogen to carbon dioxide and water from complete oxidation of glucoseOxidative phosphorylation- when oxygen accepts electrons and becomes ATP, during aerobic activity oxygen makes ATP-over 30 glucose, this is used for cell metabolism but muscle cell takes some and reserve it for body movements Special to muscle cells: creatine kinase only in cardiac and skeletal muscle cells, can take creatine molecule and grabs phosphate for it from hydrolyzed ATP Creatine and ATP= creatine phosphate and ADPCP is a phosphogen- donates phosphate back to ADP to make ATP- unique characteristic! High energy bond between creatine and phosphate so it can rephosphorylate ADP to make ATPEnzymes- can catalyze a reaction in both directions, does not participate in the reactionIf high levels of ADP and CP- enzyme reverses and products and reactants switch- makes ATP and creatineMitochondria- powerhouse of cell, where new ATP is made constantly Cycle- creating phosphate shuttleSarcoplasmic creatine kinaseCreatine kinase at rest always seeing new ATP and takes phosphate off to transfer to creatine and make creatine phosphate store (at rest) in vicinity of myosin headsIn movement- do not have enough ATP for myosin heads, creatine phosphate stored in large supply, it runs out when in motion and ATP falling because it is being broken down-so ADP is going up, and kinase conducts reaction backwards to give myosin heads ATPMoves from mitochondria to myosin heads- shuttling phosphates from ATP to reserve it for myosin head cycling, make it when and where you need itMitochondria, CP store, myosin heads get ATP, creatine= creatine kinase regulating all of this!Stop, slow down, go anaerobic- when run out of storesBIRDS EYE VIEW- using aerobic capacity and glucose-pyruvic acid to supply movement Glucose- 6 carbon sugar, starting product of glycolysis, what body mainly uses, end product of glycolysis is 2 pyruvic acids- 3 carbon molecule, made ATP in the process- pyruvic acid goes to mitochondria Oxygen gives waste products of carbon dioxide and water11/18Muscle cells don’t store ATP, do store glucose and oxygen- two reactions for glycolysis (myoglobin, glycogen)Keep ATP at constant level- benchmark for metabolismATP provides energy to live for cells, and is made fast at a specific time for muscle movement- filament sliding“creatine phosphate shuttle”- take high energy phosphate from mitochondria through creatine kinase to make creatine phosphate store for