WK5 Serotonergic Transmission (Ben) Flashcards
The serotonergic system consists of _________ axons from the cell bodies in the __________.
(Super general statement from the slides…)
The serotonergic system consists of ascending axons from the cell bodies in the raphe nuclei.
What is the 1st step in the synthesis of serotonin?
Tryptophan Hydroxylase hydroxylates the benzen ring of tryptophan’s indole side chain to produce…
5-HTP (5-hydroxyl tryptophan)
![](https://s3.amazonaws.com/brainscape-prod/system/cm/182/504/831/a_image_thumb.png?1457198044)
What is the co-factor for tryptophan hydroxylase?
Just as with tyrosine hydroxylase…
tetrahydrobiopterin
(–> dihydrobiopterin after reaction)
What is the 2nd step in serotonin synthesis?
AAA decarboxylase removes the carboxyl group of 5-HTP to make…
serotonin (5-hydroxy tryptamine, 5-HT)
![](https://s3.amazonaws.com/brainscape-prod/system/cm/182/505/154/a_image_thumb.png?1457198052)
What is the co-factor for AAA decarboxylase?
PLP
What other amino acids use identical transporters to the Trp transporter to get into the brain?
Phe, Leu, Met
(this is all the slide said on this… not sure if it means they actually all use the same transporter… maybe leading to competition… or if they each have their own, but there is homology btwn them)
In what kind of cells is Trp hydroxylase found?
only in serotonergic neurons
(this is according to the slide, BUT there are 2 isoforms… TPH 1 is in peripheral serotonogenic tissues such as the GI tract, whereas TPH2 is the neural-only form)
What is the Km for Trp hydroxylase?
And what does this mean for its function in the brain?
(the number is probably not that important, but learn it anyway!)
30-60 micromolar
- at normal physiological Trp concentrations in the brain, the enzyme is not saturated, so eating more tryptophan can -> increased synthesis of serotonin
How is Trp hydroxylase regulated on a short-term basis?
Via stimulatory phosphorylation
- PKA and CAMK2 (calmodulin-dependent) can phosphorylate its regulatory domain’s Ser residues and increase its activty
this is a placeholder for a card about long term upregulation of Trp OHase
dont get what the slide says about it… not very detailed
OK
What is the 1st step in melatonin synthesis (starting from serotonin) ?
5-HT N-Acetyltransferase adds an acetyl group onto serotonin’s amine group, producing…
N-acetyl serotonin
(AKA Serotonin N-Acetyltransferase or SNAT)
![](https://s3.amazonaws.com/brainscape-prod/system/cm/182/506/239/a_image_thumb.png?1457199670)
What is the 2nd (and final) step of melatonin synthesis?
Methylation of indole hydroxyl group of N-acetyl serotonin via the enzyme 5-hydroxyindole O-methyltransferase, producing…
melatonin.
![](https://s3.amazonaws.com/brainscape-prod/system/cm/182/506/518/a_image_thumb.png?1457199820)
What is the co-factor of 5-HT N-acetyltransferase?
(not in the slides but simple if you think about its function)
It needs acetyl-CoA to perform its acetylation reaction.
The rxn results in an acetylated product and release of CoA-SH.
What is the cofactor of the last enzyme in the synthesis of melatonin?
(also not in the slides, but simple if you think about it)
The enzyme is 5-hydroxyindole O-methyltransferase, so…
the cofactor is SAMe (S-adenosyl methionine).
(S-adenosyl homocysteine is produced.)
What is the regulatory step of melatonin synthesis?
How is it regulated?
The 5-HT N-acetyltransferase step is regulated by…
- Decreased light to the retina…
- Relay via suprachiasmatic nucleus…
- Increased NE stimulation of beta adrenergic-receptors in pineal…
- cAMP increase –> PKA –>
- phosphorylation and activation of the enzyme