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About Endogenous DMT, 5-MeO-DMT, and Bufotenine.
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lets wait to see if anybody can get access to that article and see what it says 
I'm interested in this aswell, so 5-MeO-DMT is definitely endogenous?
Toastus said:
HIOMT, EC# 2.1.1.4
something tells me this enzyme has its hands in the production of other methylated tryptamines
Hi peeps, I appreciate this thread is half a decade old now, but I've been researching endogenous production of 5-MeO-DMT and my googling led me here! The mentioned paper, "Biogenesis of 5-methoxy-N,N-dimethyltryptamine in human pineal gland" is attached.
entheogenic-gnosis
Rising Star
Toastus said:
What about SAM?
In the biosynthetic pathway for DMT it's the indole amine methyl transerase S-Adenosyl methionine that donates methyl groups (becoming S-Adenosyl-homocysteine as it donates its methyl group) to tryptamine and NMT to give DMT...
Nyctohemeral rhythm in the levels of S-adenosylmethionine in the rat pineal gland and its relationship to melatonin biosynthesis - PubMed
Liquid chromatographic techniques that permit the simultaneous analysis of S-adenosylmethionine, melatonin, and its intermediary metabolites N-acetyl-5-hydroxytryptamine and 5-hydroxytryptamine within individual pineal glands have been developed. S-Adenosylmethionine has been shown to undergo a...
www.ncbi.nlm.nih.gov
Regulation of rat pineal hydroxyindole-O-methyltransferase: evidence of S-adenosylmethionine-mediated glucocorticoid control - PubMed
Rat pineal hydroxyindole-O-methyltransferase is controlled similarly to adrenal medullary phenylethanolamine N-methyltransferase. S-adenosylmethionine (SAM), the in vivo cofactor utilized by the enzyme to convert N-acetylserotonin to melatonin, protects this methyltransferase against tryptic...
www.ncbi.nlm.nih.gov
-eg
SAM is only a cofactor, and is not specific to INMT. It likely has a role in post-translational modification as well.
entheogenic-gnosis
Rising Star
benzyme said:
Could you please elaborate?
I've been trying to understand this for a while...
So SAM is not responsible for the methylation of 5-meo-DMT in its biosynthetic pathway?
-eg
SAM is not the biological machine behind methylation, INMT is. SAM merely provides the methyl group.
in the pineal, the known methylating enzyme is HIOMT.
in the pineal, the known methylating enzyme is HIOMT.
entheogenic-gnosis
Rising Star
benzyme said:
Ok, so it's the INMT that facilitates the SAM donating it's methyl group (becoming SAH)?
In the biosynthetic pathway to DMT, tryptophan is decarboxylated (amino acid decarboxylase) to tryptamine (releasing CO2), this tryptamine is then methylated by indole amine methyl transerase (INMT) through S-Adenosyl methionine (SAM), which becomes S-Adenosyl-L-homocysteine (SAH) as it donates the methyl group to the amine nitrogen of the tryptamine, giving N-methyl-tryptamine, which is again methylated by SAM (giving SAH as it donates the methyl group to the amine nitrogen of the N-methyl-tryptamine) giving N,N-Dimethyltryptamine...
So, 5-meo-DMT relies on a different pathway, no?
--------
Misc....
-eg
yes it does.
L-Trp --4.1.1.28--> tryptamine-- 2.1.1.49 + SAH --> NMT--2.1.1.49 + SAH--> DMT.
this pathway is separate from what occurs downstream, metabolically speaking.
after 5-hydroxylation, HIOMT does the methylation.
L-Trp --4.1.1.28--> tryptamine-- 2.1.1.49 + SAH --> NMT--2.1.1.49 + SAH--> DMT.
this pathway is separate from what occurs downstream, metabolically speaking.
after 5-hydroxylation, HIOMT does the methylation.
entheogenic-gnosis
Rising Star
benzyme said:
Thank you again, I'm sorry for asking you to explain all this, it's one of those things that I have a grasp on, but need some work regarding getting the details straight, thanks again.
So, you could have this as a potential pathway?
I apologize for the looks of my pathway, it was the closest I could make it using type text, the vertical lines are the stem of the arrow and the "V" are the arrow points, I know it looks bad, but you get the idea right?...
tryptophan
|
|(tryptophan hydroxylase)
|
V
5-hydroxy-tryptophan
|
|(amino acid decarboxylase)
|
|
V
5-hydroxy-tryptamine
|
|Hydroxyindole O- methyltransferase (HIOMT)
|
V
5-methoxy-tryptamine
--- SAM
I | /
N ||
M | \
T | > SAH
··V
5-methoxy-N-methyl-tryptamine
--- SAM
I | /
N ||
M | \
T | > SAH
··V
5-methoxy-N,N-Dimethyltryptamine
Is this a reasonable pathway?
-eg
From Dr Steven Barker:
"The '76 article [Biogenesis of 5-MeO-DMT in human pineal gland] showed that the pineal had the capacity to synthesize 5-MeO-DMT but did not actually demonstrate its formation in vivo. The only results I know of that demonstrated its presence are listed in my review (attached). When we perfused pineal glands in live rats we found no evidence but 5-MeO-DMT but did see DMT, melatonin, TA, etc.
As you will see from the review, most of the studies were not conducted with adequately sensitive or specific methods and I have real doubts about the results. There has been mass spectrometric identification of 5-MeO-DMT in cerebrospinal fluid in two studies by the same group, so it is probably there somewhere!"
"The '76 article [Biogenesis of 5-MeO-DMT in human pineal gland] showed that the pineal had the capacity to synthesize 5-MeO-DMT but did not actually demonstrate its formation in vivo. The only results I know of that demonstrated its presence are listed in my review (attached). When we perfused pineal glands in live rats we found no evidence but 5-MeO-DMT but did see DMT, melatonin, TA, etc.
As you will see from the review, most of the studies were not conducted with adequately sensitive or specific methods and I have real doubts about the results. There has been mass spectrometric identification of 5-MeO-DMT in cerebrospinal fluid in two studies by the same group, so it is probably there somewhere!"
entheogenic-gnosis said:
expression of iNMT in the pineal gland is low compared to peripheral tissue epithelial cells, but being that there is a path to the gland that lacks BBB, it is possible for the protein to transport there and catalyze the methylation reactions.
yes, that is the general scheme, and is probably depicted in the KEGG pathway, sans cofactors.