amino acid transmitter pharma

Question 1

what are the amino acid neurotransmitters

Answer 1

glutamate, GABA, glycine

Question 2

how is glutamate synthesised and transported into vesicles

Answer 2

glutamate derived from food and metabolism in cells

taken up from extracellular space by reuptake via excitatory amino acid transporters (EAAT1-5)

concentrated into vesicles in glutamatergic neurones via vesicular glutmate transporter (VGLUT)

Question 3

how is GABA synthesised and transported into vesicles

Answer 3

synthesised from glutamate by glutamic acid decarboxylase (GAD)

taken up from extracellular space by reuptake via GABA transporters (GAT1-4)

concentrated into vesicles in GABAergic neurones via vesicular inhibitory amino acid transporter (VIAAT)

Question 4

how is glycine synthesised and transported into vesicles

Answer 4

taken up from blood or synthesised by all cells

taken up from extracellular space by reuptake via glycine transporters (GlyT-1and2)

concentrated into vesicles in glycinergic neurones via VIAAT

(some neurones release both GABA and glycine)

Question 5

describe the structure of LGIC glutamate receptors

Answer 5

tetrameric

contain 3 transmembrane alpha helices labelled M1-4

M2 does not cross membrane entirely but is a loop that enters intracellularly and leaves intracellularly

L-glutamate is agonist of glutamate receptors, D-glutamate is not

Question 6

describe AMPA receptors

Answer 6

GluR1-4

causes increase in sodium/potassium flux

Question 7

describe NMDA receptors

Answer 7

NR1, NR2A, NR213, NR2C, NR2D, NR3

causes increase in sodium/potassium/calcium flux

normally blocked by magnesium. depolarisation of membrane causes unblocking, relief of Mg block leads to further depolarisation, voltage gated

presence of extracellular glycine is necessary for activation (co-agonist)

Question 8

what types of kainate receptors are there

Answer 8

GluR5-7 and KA1-2

cause increase in sodium/potassium flux

Question 9

describe metabotropic glutamate receptors

Answer 9

mGluR1-8

3 groups of mGluR

group 1: mGluR 1 and 5, excites phospholipase C causing increase in IP3 and DAG (Gq)

group2: mGluR2 and 3, inhibits adenylyl cyclase, Go

group 3: mGluR4 and 6-8, also causes inhibition of adenylyl cyclase, Go

(group 2 and 3 differ in agonist selectivities)

Question 10

describe ionotropic GABA receptors

Answer 10

GABAa has variety of subunits (alpha1-6, beta1-3, gamma1-3, delta, epsilon, pi, tau and rho1-2)

pentameric LGIC

causes increase in intracellular chloride

GABAc also LGIC

Question 11

describe metabotropic GABA receptors

Answer 11

GABAbR1-2

opens potassium channels causing decrease in intracellular potassium

reduces intracellular calcium and cAMP

Gi/o

may be pre or post synaptic receptors,

pre synaptic GABA receptors reduce calcium concentration

postsynaptic cause efflux of potassium from cell

Question 12

describe glutamate metabolism

Answer 12

alpha-ketoglutarate is converted to glutamate via glutamate dehydrogenase

alpha-ketoglutarate is produced by citric acid cycle

glutamate is converted to glutamine via glutamine synthase

glutamine is converted to glutamate via glutaminase

Question 13

name modulators of GABAa receptors

Answer 13

benzos, barbiturates, steroids, alcohol, anaesthetics

benzos are positive allosteric modulators of GABAa receptors

Question 14

describe GABA metabolism

Answer 14

glutamate is converted into GABA via glutamic acid decarboxylase

GABA is converted into succinic semialdehyde via GABA transaminase