Neurobiology: Neurochemistry Answers

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NT (compared to hormone)
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shorter distance, latency, duration more focal
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*small molecules*
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classical NT
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amino acids
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glutamate (GABA) gamma-aminobutyric acid glycine
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amines
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modified AA acetylcholine biogenic: (catecholamine) DA, NE, EPI 5-HT, histamine
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*large molecules*
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peptides
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strings of AA, [smallest] in brain opioids: analgesic; internal heroin beta-endorphin, leu-enkephalin, met-enkephalin, dynorphin substance P, oxytocin, vasopressin, neuropeptide Y, somatostatin, vasointestinal polypeptide, cholecystokinin
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*purines*
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adenosine, ATP methylxanthines (receptor blockers): caffeine, theophylline, theobromine
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*atypical*
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nontraditional gases: NO, CO cannabinoids: anandamide, 2-arachidonylglycerol
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co-localization
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aka co-release, co-transmission ~2-4 NT released at one bouton (in different vessicles)
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co-packaging
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aka co-storage different NT in same vessicle
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*NT life cycle*
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synthesis > storage > release/reception > inactivation
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synthesis
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small NT: -substrates in all neurons, different enzymes produce the individual or combination NT -typically cytosolic > made at terminal near release site > transported into vesicle (ATP dependent) large NT: -pro-peptide made in cell body > vesicle > precursor convertases cleave NT from pro-peptide in vesicle > transport to terminal > release
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storage
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vesicular storage- protect from degradative enzymes in cytosol
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release (small molecule)
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quantal, Ca dependent, exocytosis rest: reserve pool (storage) bound, releasable pool docked near Ca channel (active zone) depolarized (AP): Ca channel open > Ca influx > reserve pool detach, primed vessicles fuse with bouton > exocytosis fusion: v-SNARE + t-SNARE > SNARE complex > priming > Ca bind synaptotagmin (vesicle receptor) > fusion > exocytosis *C. botulinum toxin acts as a protease to degrade SNARE complex > prevent priming > block NMJ transmission (paralysis)
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release (large molecule)
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high AP activity, require more Ca larger vesicles, release at distant regions from active zone
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vesicle retrieval
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small molecule: endocytosis > reformed > refilled > reused large molecule: retrieved but not reused
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reception
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ionotropic: several protein subunits chemically gated ion channel (NT activation) spatially local, short action/duration metabotropic: second messenger (G-protein most common) > downstream physiological changes single protein crossing membrane 7x greater variety of changes (protein function/synthesis, tx, ion channels), spatial extent, longer latency/duration
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GPCR
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NT binds GPCR > activate enzyme > conversion to second messenger cAMP system: NE binds beta-adrenergic receptor > G protein activated > adenylyl cyclase activated > ATP conversion to cAMP > protein kinase A activated > phosphorylation > change protein function
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inactivation
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diffusion from synapse (not efficient) transporter reuptake of small NT (*NOT ACh) AChE degrades ACh > choline + acetate peptide diffuses to peptidase for break down

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