STAT 1100 Lecture Notes - Lecture 3: Reuptake, Retina, Cell Signaling
1
Amino acid neurotransmitters
›Non-essential amino acids
»Not required in diet
»Synthesized in most cells of the body
›Two functional groups
»Excitatory amino acid NT
‒Glutamate, Aspartate, Cysteate, Homocysteate
»Inhibitory amino acid NT
‒γ-aminobutyric acid (GABA), Glycine, Taurine, Alanine
Aspartate ->Not considered a ‘classic’ neurotransmitter
›Released in a Ca2+-dependent manner
›May not be stored in secretory vesicles
›May be directly released from cell cytoplasm
Glutamate
›Acts at glutamatergic receptors
›Physiological functions unclear
›Most widely used excitatory neurotransmitter
›~90% of all neurons, 80-90% of all synapses are glutamatergic
›Mediates fast excitatory neurotransmission
»Sensory, motor coordination, emotion, cognition, memory
formation and retrieval
›Proteinogenic amino acid
»Abundant throughout the cell
»Concentrated in presynaptic compartments-> In a specific manner
and with Ca+ dependent manner
Proteinogenic = amino acids used to create proteins, any of the 20 amino acids
encoded by DNA
Glutamate is the anionic salt of glutamic acid.
»Glutamate is the only form found in vivo as it is deprotonated at any pH
above the pKa of 4.1
Glutamate synthesis from
glutamine
In the CNS the majority of
glutamate is recycled from
glutamine by the enzyme
glutaminase
Glutamate is metabolized to
glutamine
Glutamine synthetase is the
enzyme responsible for
conversion of glutamate to
glutamine. —>moves back and forth between glutamate and glutamine
Glutamate synthesis via Kreb’s cycle
An intermediate in the Kreb’s cycle (α-ketoglutarate) can serve as an immediate
precursor to glutamate for de novo synthesis. α-ketoglutarate is metabolised by
any of several amino acid transaminases (plus the corresponding amino acid) to
yield glutamate plus an α-keto acid.
most of the time its recycled but can be done like this if needed
Glutamate transporters
›Glutamate is abundant throughout the cell
›Neurotransmitter glutamate is packaged into vesicles to maintain a separate
‘pool’ of NT
›Vesicular glutamate transporter (VGLUT) can be used to identify
glutamatergic neurons
»Family of 3 transporters
›VGLUTs are structurally and functionally similar to VMAT
›VGLUT1 and 2 are expressed on distinct glutamatergic populations in the
CNS.
›VGLUT3 is expressed in various neurons including GABAergic, cholinergic,
and monoaminergic neurons suggesting possible modulatory functions.
