Week 5: Neurotransmitter Synthesis and Pathways Flashcards
Classes of Neurotransmitter
- Acetylcholine (ACh)
- the Biogenic Amines
- the Amino Acids
- Neuroactive Peptides
Biogenic Amines
- Dopamine (DA)
- Norepinephrine (NE)
- Sertonin (5HT)
- Histamine
Amino Acids
- GABA
- Glutamate
- Glycine
Neuroactive Peptide Families
- Pro-opio-melanocortin (POMC) - contains beta-endorphin
- pro-enkephalin - contains met- and leu-enkephalins
- pro-dynorphin - contains dynorphin
4 criteria for calling a substance a neurotransmitter
- It must be synthesized in the neuron
- It must be released in sufficient amounts upon an AP to yield PSPs
- exogenous applications will mimic normal activity
- there must be some deactivating mechanism(s)
Dale’s Law
a mature neuron makes use of the name neurotransmitter in all of its synapses (original)
NEW: A mature neuron makes sure of the same combination of neurotransmitter substances in all of its synapses
Coexistance
the use of more than one transmitter by a neuron
Where does neurotransmitters synthesis occur?
All NT except neuroactive peptides: at the pre-synaptic terminal
Neuroactive Peptides: The nucleus
Synthesis of ACh
Acetyl Co-enzyme A + Choline –> Choline Acetyal Transferase (CAT) –> Acetylcholine (ACh)
Deactivating mechanism for ACh
Acetylcholinesterase (AChE)
Exists in the synapse next to the ACh receptor and exits in the terminal and on the presynaptic side of the synapse (which will break up any not-bound ACh)
The choline is recycled by a transporter on the external face of the synaptic cleft.
Critical Issues about vesicles
- they are essentially safety zones, they prevent NT from being broken down
- they are not saturated (not normally filled to capacity)
Vesicle Transporters: Proton Pumpers
Purpose: to keep the inside of the vesicle supplied with proteins
Vesicle transporters
exchange 2 protons for every molecule of NT
Types of Vesicle Transporters
- one for ACh
- One for biogenic amines (VMAT)
- One for glutamate
- One for GABA
Monoamine Neurotransmitters
- Catecholamines
- Dopamina (DA)
- Norepinephrine (NE) - Indoleamines
- Serotonin (5HT)
Dopamine Synthesis Pathway
Tyrosine –> L-DOPA (via tyrosine hydoxylase) –> Dopamine (via dopa decarboxylase)
Rate Limiting Enzyme for Catecholamines
tyrosine hydroxylase exists in an inactive form and needs pteridine-H4 cofactor to become active
Pteridine-H4 then becomes pteridine-H2 and pteridine reductase will then add H back to pteridine to make it active and able to activate tyrosine hydroxylase again
Synthesis pathway of Norepinephrine
tyrosine –> L-Dopa (via tyrosine hydroxylase) –> Dopamina (via dopa decarboxylase) –> Norepinephrine (via dopamine beta hydroxylase)
Deactivating Mechanism for Monoamines
Re-uptake - the drawing of NT molecules back into the pre-synaptic membrane via membrane transporters
General classes of membrane transporters
- Ones Glutamate
2. Ones for GABA, glycine, norepinephrine (NET), dopamine (DAT), serotonin (SERT), and choline
Similarities of general classes of membrane transporters
- they are both driven by the Na+ concentration gradient
2. they both co-transport another ion
Dissimilarities of general classes of membrane transporters
- the glutamate transporter is made up of a protein that spans the membrane 6-8 times; the others span the membrane 12 times
- Glutamate transporter requires the co-transport of K+; the others require the co-transport of Cl-
Enzymes that break down Catecholemines
- Monoamine oxidase (MAO)
- Catechol-o-methyl-transferase (COMT)
Both exist in the terminal and on the pre-synaptic side (where they break down free NT)
Short term feedback systems of catecholamines
- end product inhibition (inhibition)
2. Ca++ feedback (excitation)