Drug Targets Cheat Sheet

Drug Targets Study online at https://quizlet.com/_eode5x 1. What are the four ligand gated ion channels main types of re- G protein coupled receptors ceptor? kinase receptors nuclear receptors 2. What is an agonist drug? substance that binds and activates a receptor leading to a biological response 3. What is an antag- substance that binds to a receptor to inhibit a biological onist drug? response 4. Name 4 examples nicotinic of ligand gated GABA ion channels. glutamate purinergic 5. Where are ligand found on the plasma membranes of cells in the neuromusgated ion chan- cular junction, autonomic ganglia, and in the CNS nels found? 6. What binds to extracellular ATP purinergic receptors? 7. How do ligand gated ion channels work? 1. ligand binds to allosteric complementary site on the ion channel 2. ion channel undergoes conformational change and opens so ions can enter or leave the cell 3. ion permeability increases generating a possible action potential, by depolarising the inside of the membrane 4. ion channel closes when ligand unbinds 8. What binds to nicotinic receptors? nicotine acetylcholine 9. What happens it causes the ion channel to open and increase the plasma when acetylmembrane's Na+ and K+ permeability, so the cell is decholine binds to polarised and the probability of an action potential being generated is increased 1 / 11 Drug Targets Study online at https://quizlet.com/_eode5x a nicotinic receptor? 10. What is the func- to transmit action potentials conducted along motor tion of the NMJ? nerves, across synaptic clefts that occur in motor endplates 11. What does the invaginations which increase SA and therefore increase postsynaptic re- its exposure to acetylcholine gion of the sarcolemma contain which increases its total SA? 12. What is myasthe- an autoimmune chronic disease of weakened skeletal nia gravis? muscles and abnormal fatigue 13. Where does in the motor neurone terminal acetylcholine synthesis occur? 14. What is acetylcholine catalysed by? the cytosolic enzyme choline acetyltransferase 15. Describe neuron transmission at a neuromuscular junction. 1. action potential is transmitted along somatic nerves to the postsynaptic neuron. 2. acetylcholine synthesis occurs in the motor neurone terminal and is catalysed by choline acetyltransferase. 3. the acetylcholine is then stored in vesicles ready for release. 4. when action potentials reach their nerve terminals, depolarisation causes an influx of calcium ions. 5. this triggers acetylcholine release into the synaptic cleft due to vesicles fusing with the membrane. 6. released acetylcholine can now diffuse across the synaptic cleft and bind to nicotinic receptors on the sarcolemma, causing a depolarisation, which if large enough can stimulate an action potential in the muscle fibre, causing it to contract. 2 / 11 Drug Targets Study online at https://quizlet.com/_eode5x 7. acetylcholinesterase in the synaptic cleft hydrolyses acetylcholine stopping the neurotransmission 16. Describe acetyl- acetyl groups are donated by acetyl coenzyme A, which choline synthe- are then covalently bonded to choline to form acetylsis. choline 17. What does acetylcholinesterase hydrolyse acetylcholine into? choline and acetic acid 18. Name four examples of G-protein coupled receptors. muscarinic adrenergic purine dopaminergic 19. What are G-pro- alpha subunits teins made up beta subunits of? gamma subunits 7 transmembrane spanning regions that are connected by extracellular and intracellular loops 20. What happens they form a complex together and freely move about in the to the beta cell's plasma membrane and gamma subunits? 21. Why can beta because they are both very hydrophobic and gamma subunits freely move about in the cell's plasma membrane? 22. What are the it can bind to guanine nucleotides three properties it forms a loose association with the beta/gamma complex it has the ability of catalysing the hydrolysis of GTP to GDP 3 / 11 Drug Targets Study online at https://quizlet.com/_eode5x of the alpha subunit? 23. What are GTP and GDP? guanine nucleotides 24. Describe the acti- 1. a drug binds to the GPCR. vation of GPCRs. 2. the alpha subunit then releases its GDP and binds instead to GTP. 3. this activated alpha subunit now dissociates from the receptor and its beta/gamma complex, allowing it to diffuse across the membrane surface to stimulate its target protein. 4. the alpha subunit hydrolyses the bound GTP to GDP and an inorganic phosphate, terminating the alpha subunit's activation. 5. the alpha subunit can then re-associate with the beta/gamma complex and the process is ready to be repeated. 25. What are the Gs three types of G Gi protein? Gq 26. What do Gs pro- stimulate targets teins do? 27. What do Gi proteins do? inhibit targets 28. What do activat- activate phospholipase C ed Gq proteins do? 29. What are the three main targets of G proteins? ion channels the cAMP system the phospholipase C system 30. 4 / 11 Drug Targets Study online at https://quizlet.com/_eode5x Where are mus- found on cells and tissues innervated by the parasympacarinic receptors thetic nervous system found? 31. What binds to muscarinic receptors? acetylcholine 32. What are the nicotinic two subtypes of muscarinic cholinergic receptor? 33. Describe how targeted muscarinic receptors cause the parasympathetic nervous system to relax. 1. Muscarinic receptors in the heart are stimulated by acetylcholine. 2. this activates G proteins to open potassium channels. 3. potassium ions diffuse out of the cell down their concentration gradient. 4. this hyperpolarisation makes it harder for muscle cells in the heart to become depolarised and contract. 34. What to adrener- noradrenaline gic receptors re- adrenaline spond to? 35. What happens vasoconstriction when alpha-1 adrenergic receptors are activated? 36. What happens reduction of sympathetic outflow when alpha-2 adrenergic receptors are activated? 37. What happens when beta-1 adrenergic re- increasing heart rate 5 / 11 Drug Targets Study online at https://quizlet.com/_eode5x ceptors are activated? 38. What happens vasodilation and bronchodilation when beta-2 adrenergic receptors are activated? 39. What is the main hormone that binds to kinase linked receptors? insulin 40. Where are kinase found bound to membranes linked receptors found? 41. Describe the structure of kinase linked receptors. possess extracellular and intracellular domains these two domains are connected together by a single alpha helix that spans the thickness of the membrane 42. What does kinase linked receptors' extracellular domain form? the receptor's ligand binding sites 43. What does kinase linked receptors' intracellular domain form? tyrosine kinase enzyme ATP binding site 44. Why does ligand because only a very simple alpha helix connects these two binding to the together extracellular domain not result 6 / 11 Drug Targets Study online at https://quizlet.com/_eode5x in a conformation change in the intracellular domain? 45. What mechanism do cytokines use? a tyrosine phosphorylation mechanism 46. Describe the activation of kinase-linked receptors. 1. ligand binds to extracellular site on the receptor. 2. this results in dimerization. 3. this allows for autophosphorylation of the tyrosine kinase enzyme. 4. intracellular proteins containing SH2 domains bind to the phosphorylated tyrosine in the intracellular domain. 5. these bound SH2 domain containing proteins now become activated and influence transcription and translation of proteins. 47. What is dimeriza- where two receptors pair to form a dimer tion? 48. Describe a phosphate group is donated to the receptor by the bound autophosphoryla- ATP tion of tyrosine kinase enzyme. 49. Describe the comprised of four glycoprotein molecules structure of an made up of 2 alpha and 2 beta subunits insulin receptor. the subunits contain cysteine residues 50. What do cysteine enable the formation of disulphide bridges which is imporresidues do (in tant for keeping the complex bound together an insulin receptor)? 51. Describe the alpha subunits in insulin receptors. extracellular form the insulin binding site 7 / 11 Drug Targets Study online at https://quizlet.com/_eode5x 52. Describe the beta have both extracellular and intracellular domains subunits in init is their intracellular portion that possesses tyrosine kisulin receptors. nase activity 53. What happens when insulin binds to its receptor? the beta subunit autophosphorylates, which enhances the kinase activity of other target proteins 54. Are nuclear re- intracellular ceptors intracellular or extracellular? 55. What are nuclear receptors involved with? regulating DNA transcription 56. What hormones steroid hormones and thyroid hormones bind to nuclear receptors? 57. What are horendocrine glands mones produced by? 58. What do hormones do? modify the structure or function of specific organs or tissues 59. What are nuclear large monomeric proteins receptors? 60. What does the a highly conserved region that contains two finger shaped middle portion of loops of peptide chain (zinc fingers) a nuclear receptor contain? 61. Why are the fin- because each finger contains a zinc ion, which is held in ger shaped loops place by 4 cysteine residues 8 / 11 Drug Targets Study online at https://quizlet.com/_eode5x of peptide chain called zinc fingers? 62. What does the zinc finger domain form? the receptor's DNA binding region since the fingers are believed to be able to wrap around DNA helixes 63. What does the the steroid binding domain carboxyl end of a nuclear receptor contain? 64. What is the amino acid end of a nuclear receptor? the receptor's regulatory domain that can activate the transcription of specific genes 65. Why do nubecause nuclear receptors are intracellular - so the ligands clear receptors' have to be lipid soluble so that they can pass through a ligands have to cell's plasma membrane be lipid soluble? 66. Describe steroid highly lipid soluble molecules. easily gain access to the intracellular compartment where they can bind to their receptors located in the nucleus 67. What happens when a steroid binds to its receptor? it induces a conformational change in which the receptor unfolds to expose the zinc finger domain 68. What can can now bind to specific portions of DNA ligand/receptor complexes bind to once a steroid has bound to the receptor? 69. 9 / 11 Drug Targets Study online at https://quizlet.com/_eode5x What happens results in production of mRNA when there is an this mRNA leaves the nucleus to form a complex with increased RNA ribosomes, enabling the synthesis of protein polymerase activity? 70. What are enzymes? the catalysts of biological systems 71. What are catalysts? substances that alter the rate at which a chemical reaction occurs but is itself not used up or changed 72. Define activation chemical reactions require a certain amount of energy to energy. get underway 73. What does com- involves substrate and inhibitor molecules competing for petitive inhibition the occupancy of the enzymes' active sites involve? 74. What does non-competitive inhibition involve? involves the inhibitor and substrate binding simultaneously to an enzyme the inhibitor binds to an allosteric site on the enzyme and changes the conformation of the enzymes' active site, meaning the substrate can no longer bind 75. Describe how en- 1. substrate binding occurs at the active site. zymes work. 2. the enzyme-substrate complex undergoes an internal rearrangement to form the product. 3. the products of the reaction are then released. 76. What do carrier molecules do? carry molecules across the lipid bilayer that are too polar to cross on their own 77. Give 3 examples ions transporters of carrier mole- glucose transporters cules. amino acid transporters 78. What do carrier molecules contain? contain recognition sites that are specific for the particular particle that they have to transport 10 / 11 Drug Targets Study online at https://quizlet.com/_eode5x 79. How do anticholinesterases work? work by inhibiting the enzyme acetylcholinesterase, which is normally responsible for hydrolysing acetylcholine into choline and acetate they prolong the presence of acetylcholine in cholinergic synaptic clefts so increase acetylcholine's effect 80. What areas do autonomic cholinergic synapses antineuromuscular junctions cholinesterases CNS affect? 81. What do monoamine oxidase enzymes do? catalyse the conversion of catecholamines to aldehydes and so they are important for the degradation of neurotransmitters 11 / 11