22- Glycine

Question 1

what is glycine?

Answer 1

second major inhibitory neurotransmitter of the CNS

found in ventral horn of the spinal cord (location for spinal interneuron terminals) = inhibits AP firing

Question 2

describe glycine synthesis

Answer 2

3-phopshoglycerate converted to serine by glycolysis

serine to glycine by serine hydroxymethyltransferase

Question 3

describe glycine transport into synaptic vesicles

Answer 3

transported by VIAATs = vesicles become oval shaped

Question 4

describe glycine re-uptake from the synaptic cleft

Answer 4

reuptake by GlyT transporters - different isoforms exist:
in neurons = Gly-2
in glial cells = Gly-1

high affinity Na+ dependent co-transporters

Question 5

describe glycine degradation

Answer 5

can occur by various pathway involving various enzymes - main method is the reversal of glycine biosynthesis

glycine converted to serine by serine hydroxymethyltransferase

Question 6

describe glycine receptors

Answer 6

LGICs, pentameric, consisting of alpha and beta subunits of various subtypes

common configurations:
- 3A, 2B
- 4A, 1B

unsure of binding site for glycine

glycine binds to the receptor - ion channel opens allowing Cl- influx, hyperpolarisation, inhibits AP firing and generation

Question 7

what can be inferred by glycine’s role in NMDA receptors?

Answer 7

glycine binds to the N1 subunit of glutamate NMDA receptors = controls the timing and amplitude of ion channel opening

acts as a co-factor for the NMDA receptor

Question 8

what is hyperekplexia?

Answer 8

disorder characterised by hypertonia in response to unexpected stimuli, producing an exaggerated startle response

Question 9

how is hyperekplexia related to glycine?

Answer 9

gene mutations in glycine receptors/ transporters affect normal glycinergic transmission

increase neuronal hyperexcitability = leads to hypertonia and decreased muscle Cl- conductance