SM02 Mini3 Flashcards Preview

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Flashcards in SM02 Mini3 Deck (48):
1

general properties of neurotransmitters

  • small, water-soluble for fast diffusion across synaoptic cleft
  • synthesized in presynaptic cell
  • stored in synpatic vesicles
  • released in response to membrane depolarization
  • Ca2+-dependent release
  • action on postsynaptic cell via receptors
  • rapid inactivation via degradation or uptake

2

types of neurotransmitters

acetylcholine

biogenic amines

peptides

amino acids

3

how do neurotransmitters affect the postsynaptic cell?

by causing opening or closing of ion channels to depolarize or hyperpolarize the cell

4

how do excitatory neurotransmitters function?

increase Na+ permeability

causes depolarization

5

how do inhibitory neurotransmitters function?

increase Cl- or K+ permeablility to hyperpolarize the cell

6

what type of receptors do neurotransmitters use?

  • GPCR
    • adrenergic
    • dopamine
    • muscarinic
    • opiate
  • ligand-gated ion channels
    • nicotinic cholinergic
    • GABA-A

7

how & where is acetylcholine synthesized?

in the axon terminal

Acetyl-CoA & choline combined via choline-acetyl transferase

8

what receptors does ACh work thru?

  • nicotinic: ligand-gated Na+ channel
    • found in NMJ, autonomic ganglia, & brain
  • muscarinic: GPCR that either forms IP3 or lowers cAMP levels
    • found in parasympathetic nervous tissue, sweat glands & brain

9

how is aceylcholine degraded?

by acetylcholinesterase

serine residue in active site

enzyme found in basal lamina of NMJ & postsynaptic membrane in other synaptic clefts

2 steps: choline release & acetyl group binds at O of serine residue side chain, then water comes in to restore enzyme & forming acetic acid

10

how is aceylcholinesterase inactivated?

by organophasphates

causing irreversible inhibition

serine O at active site binds to phosphate group

11

what is the effect of organophosphate poisoning?

ACh accumulation in the synaptic cleft 

increased excitatory activity

producing excessive parasympathetic activity (GI motility, salivations & secretions)

12

what are the types of biogenic amines?

catecholamines

indolamines

histamine

13

where do biogenic amines come from?

decarboxylation of amino acids

14

what are the major catecholamines?

dopamine

norepinephrine

epinephrine

15

how are the catecholamines synthesized?

from tyrosine

  • tyrosine hydroxylation→ L-DOPA (dihydroxyphenylalanine)
    • requires O2 & BioH4 (also for phenylalanine tranformation to alanine)
  • dopa decarboxylase→ dopamine
    • releases CO2
    • requires B6
  • oxidation→ norepinephrine
    • requires Cu+, ascorbate, & O2
    • releases H2O
  • methylation→ epinephrine
    • S-adenosyl-methionine is methyl donor
    • becomes S-adenosyl-homocysteine

16

where is norepinephrine & epinephrine made?

locus coeruleus: nucleus in pons

adrenal medulla

17

how are the catecholamines inactivated?

mostly by reuptake via high affinity Na+-dependent cotransporters

inactivation axon terminal:

  • MAO: oxidative deamination by monoamine oxidase
    • uses FAD & water
    • releases NH4+
  • COMT: methylation by catechol-O-methyltransferase
    • SAM is methyl donor
    • acts on hydroxy groups of ring structure
  • rxns can occur in either order

18

where is the MAO enzyme located?

w/in the mitochondrial outer membrane

19

what are the main indolamines?

serotonin & melatonin (biological induction of sleep due to darkness)

20

how are the indolamines synthesized?

from tryptophan

  • tryptophan hydroxylase→ 5-hydroxytryptophan
    • adds -OH to benzyl ring
    • requires BioH4
  • decaroxylase→ serotonin (5-HT: 5-hydroxytryptamine)
    • generates CO2
    • requires B6
  • acetylation & methylation (via SAM)→ melatonin
    • occurs in pineal gland

21

how is serotonin inactivated?

mostly high affinity reuptake

then oxidative deaminiation by MAO

22

what is the final degradation product of dopamine that is excreted?

homovanillic acid

23

what is the final degradation product of norepi- & epinephrine that is excreted in urine?

vanillylmandelic acid

24

what is the final degradation product of serotonin that is excreted?

5-hydroxyindoleacetic acid

25

what is homovanillic acid presence in urine indicative of?

neuroblastoma or pheochromocytoma

26

what is vanillylmandelic acid presence in urine indicative of?

elevated in patient w/tumors that secrete catecholeamines

neuroblastoma or pheochromocytoma

27

what is 5-hydroxytryptamine presence in urine indicative of?

used to determine serotonin levels in the body

amt may vary w/tumors, renal malfunction, or small bowel resection

most often used for diagnosis carcinogenic tunors of enterochromaffin cells of small intestine

28

which neurotransmitters are rarely released on their own?

peptide neurotransmitters

29

how are neuropeptides synthesized?

derived from precursor proteins that are synthesized in perikaryon (soma of neuron)

transported to terminals in vesicles via fast axoplasmic transport

30

what type of receptors do neuropeptides bind?

GCPRs

31

how are neuropeptides inactivated?

by peptidases

32

endorphins

endogenous morphines

found in CNS, intestine, pituitary gland, & adrenal gland

can act as a neurotransmitter or hormone

33

Substance P

sensory transmitter of some dorsal root neurons, often w/glutamate

especially in pain fibers

also abundant in basal forebrain

34

neuropeptide Y

abundant in limbic system, hypothaalamus, cerebral cortex

stimulates food intake in hypothalamus

present in postganglionic sympathetic neurons & enteric plexuses

35

somatostatin

found in hypothalamus, limbic structures, & cerebral cortex

cotransmitter w/norepinephrine, serotonin, or GABA neurons 

36

enkephalins

pentapeptides used as neurotransmitters & in the adrenal medulla

small endorphins

Tyr-Gly-Gly-Phe-Met

Tyr-Gly-Gly-Phe-Leu

37

where are beta-endorphins made?

anterior pituitary gland

38

how do beta-endorphin structures compare to enkephalins?

Tyr-Gly-Gly-Phe-Met

Tyr-Gly-Gly-Phe-Leu

are the enkephalins

beta-endorphins are extended at the C terminus

39

why aren't endorphins addicting like their pharmacological counterparts (morphine, other opiate drugs)?

smaller dose

and endorphins are rapidly degraded by proteases whereas opiate drugs activate receptors for many hours

this causes desensitization & adaptive response

40

what are the main excitatory amino acid neurotransmitters?

glutamate & aspartate

41

what are the main inhibitory amino acid 

glycine in the spinal cord & brainstem

GABA in forebrain

42

how are the amino acid neurotransmitters inactivated?

high-affinity uptake rom synaptic cleft

 

43

how is GABA synthesized?

from glutamate

glutamate decarboxylase→ GABA

requires B6

releases CO2

44

how is GABA inactivated?

by GABA transaminase

forms succinic semialdehyde which can be transformed to enter the TCA cycle

requires B6 & alpha-ketoglutarate

45

what is teh main receptor & action of GABA?

GABA-A receptor

ligand-gated Cl- channel

inhibitory

causes hyperpolarization→ makes it harder to excite the neuron (depolarize)

46

what function does GABA have via GABA-B receptor?

GABA-B receptor is GPCR

metabotropic

metabolic implications

47

effects of high GABA activity

sedatin

anxiolytic

anticonvulsant

48