Amino-acid neurotransmission

Question 1

What are the non-essential amino-acids?

(11)

Answer 1

• Don’t need though diet, create ourselves

1. Alanine
2. Asparagine
3. Aspartate
4. Cysteine
5. Gultamate>GABA
6. Glutamine
7. Glycine
8. Proline
9. Serine
10. Tyrosine>L>DOPA>Dopa>Nora>Adre
11. Arginine

Question 2

What are the essential AA?

(9)

Answer 2

• Need to take in through diet

1. Histidine - histamine
2. Isoleucine
3. Leucine
4. Lysine
5. Methionine
6. Phenylalanine
7. Threonine
8. Tryptophn - 5-HT - Melatonin
9. Valine

Question 3

What can deficiencies of essential AA lead to?

Answer 3

• Histidine - Eczema
• Isoleucine - Similar to hypoglycaemia
• Leucine - Lethargy, weight loss
• Lysine - Loss of app, poor growth
• Methionine - Liver damage
• Phenylalanine - “, apathy, stunted growth
• Threonine - Hypo again
• Tryptophan - Aggro
• Valine - Impaired mental func

Question 4

What are Ketogenics?

Answer 4

• AA that yield acetyl CoA or acetoacetyl CoA
• Lycine and Leucine
• Don’t produce metabolites that can be conv to glucose

Question 5

What are glucogenics?

Answer 5

• AA whose catabolism yields to the formation of pyruvate or krebs metabolites
• Metabolites CAN be converted into Glucose through gluconeogenesis
• Alanine, Glutamate, Glycine, serine and like 10 more

Question 6

What are glucogenic and ketogenic AA?

Answer 6

• AA that yield some products that can become glucose and others that yield acetyl CoA or Acetoacetyl CoA
• Isoleucine, Phenylalanine, Tryptophan, Tyrosine, Threonine

Question 7

What is Glutamate?

Answer 7

• Glutamte –> Glutamine
• Present in high concs

Question 8

Explain glutamate metabolism?

Answer 8

• Glutamate can become:
  1. Cysteine
  2. Glutathione
  3. GABA
  4. Glutamine

Question 9

What is stereospecifity?

Answer 9

• Non stereo-specific effects of glutamate and aspartate.
• NMDA was more potent than L-form

Question 10

What are potent compounds?

Answer 10

• L-homocysteate
• ODAP
• Kainic acid
• Quisqualic acid
• AMPA

Question 11

What are Multiple receptor sites?

Answer 11

• Identification of multiple receptor types preceded definitive establishment of a role in glutamate in syn function

Question 12

What are the effects of Mg2+?

Answer 12

• Found to inhibit synaptic activity/reduce synaptic release of NT

Question 13

What are renshaw cells?

Answer 13

• • Added glutamate to Renshaw cells – known to respond to ACh – glutamate also excited them – he thought glutamate was having a non-specific effect so withdrew his statement even though he was right (but he thought he was wrong)

Question 14

Explain renshaw cells?

Answer 14

• The presynaptic terminal from afferent sensory information is glutamatergic, which excites the postsynaptic terminal to produce the efferent output (muscle contraction) – myotatic reflex
• Some cells in the spinal cord have a recurrent collateral – which comes off the main axon and feeds back – which releases ACh – the ACh impinges upon the Renshaw cell, which releases glycine onto the same postsynaptic membrane as glutamate – glycine is an inhibitor –
• Essentially a negative feedback loop – prevents uncontrolled excitation and limits the firing frequency

Question 15

What is Mg2+?

Answer 15

• Mg2+ binds to NMDA receptor and prev glutamate from having an effect Mg2+ abolishes NMDA response
• Kaginate + quisqualate unaffected
• L-gutamate inhibited to an intermediate degree
• Suggests kainate and NMDA bound to dif receptors

Question 16

What are NMDA antagonists?

Answer 16

• AP5
• CNQX
• Next step was that if glutamate is an NT where are the glutamatergic pathways

Question 17

Explain renshaw antagonists?

Answer 17

• can stimulate the afferent and record the efferent, or stimulate the cell in the middle and measure the effect
• Was found that individual Renshaw cells are excited by ACh and glutamate
• Renshaw cells excited by both ventral and dorsal stimulation
• D⍺AA blocked glutamate and dorsal stimulation but did not block ACh or ventral stimulation
• DHβE blocked ACh and ventral stimulation but did not block glutamate or dorsal stimulation

Question 18

What are Glutamate receptor sub-types?

Answer 18

Question 19

What is GABA?

Answer 19

• Effects known before glutamate, reasoned inhib of GABA should be excitatory, it was.

Question 20

What is Glycine?

Answer 20

Inhibitor but acts on different receptors to GABA

Question 21

How does chlorine interact with GABA?

Answer 21

• GABA can also have an excitatory effect in immature cells- due to different concentrations of chlorine in the cells

Question 22

What are GABA receptor subtypes?

Answer 22

• Ionotropic GABAa
• Metabotropic GABAb

Question 23

What are EAATs?

Answer 23

5 subtypes, belong to solute carrier 1 family (SLC.

• EAAT1 - Primarily cerebellum
• EAAT2 - Astrocytes (90% of glut uptake)
• EAAT3 - Post-synp
• EAAT4 - Purkinje
• EAAT5 - retina

Question 24

What conditions is Glutamate involved in?

Answer 24

• Excitotoxicity associated with stroke
• Schizophrenia
• Major depressive disorder and bipolar
• OCD
• Anxiety
• Drugs of abuse
• Prenatal insults
• Autism
• Dementia

Question 25

What is GABA the target for?

Answer 25

• Anticonvulsant
• Benzodiazepine
• Barbiturates
• Neurosteroids
• General anaesthetics

Question 26

What targets glycine?

Answer 26

• Tetanus toxin prev glycine release and leads to excessive reflex hyperexcitabilit and violent muscle spasms (lockjaw)