DMT-Nexus member
Posts: 34 Joined: 19-Aug-2010 Last visit: 19-Jun-2020
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But INMT isn't in the pineal, shouldn't that negate the possibility of 5-MeO being produced there? Disclaimer: Everything in these posts is based on the Heisenberg Uncertainty Principle, rendering all contents of said posts null and void.
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DMT-Nexus member
Posts: 14191 Joined: 19-Feb-2008 Last visit: 16-Apr-2024 Location: Jungle
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lets wait to see if anybody can get access to that article and see what it says 
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DMT-Nexus member
Posts: 2354 Joined: 24-Jan-2010 Last visit: 21-Jun-2012 Location: Massachusetts
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I have access to the hardcopy, I'll see about scanning it tomorrow. PK Dick is to LSD as HP Lovecraft is to Mushrooms
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DMT-Nexus member
Posts: 1178 Joined: 12-Oct-2010 Last visit: 08-Jan-2022
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I'm interested in this aswell, so 5-MeO-DMT is definitely endogenous?
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DMT-Nexus member
Posts: 2354 Joined: 24-Jan-2010 Last visit: 21-Jun-2012 Location: Massachusetts
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I went to get this hardcopy, and it had been temporarily archived due to remodeling in the library's journal area. Will check into its status again, thanks for the bump. PK Dick is to LSD as HP Lovecraft is to Mushrooms
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analytical chemist
 
Posts: 7463 Joined: 21-May-2008 Last visit: 03-Mar-2024 Location: the lab
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Toastus wrote:But INMT isn't in the pineal, shouldn't that negate the possibility of 5-MeO being produced there? HIOMT, EC# 2.1.1.4something tells me this enzyme has its hands in the production of other methylated tryptamines "Nothing is true, everything is permitted." ~ hassan i sabbah
"Experiments are the only means of attaining knowledge at our disposal. The rest is poetry, imagination." -Max Planck
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DMT-Nexus member
Posts: 2147 Joined: 09-May-2009 Last visit: 24-Mar-2024 Location: the shire, England
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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.
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DMT-Nexus member
Posts: 2889 Joined: 31-Oct-2014 Last visit: 03-Nov-2018
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Toastus wrote:But INMT isn't in the pineal, shouldn't that negate the possibility of 5-MeO being produced there? 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... https://www.ncbi.nlm.nih.gov/pubmed/7561889https://www.ncbi.nlm.nih.gov/pubmed/7452273-eg
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analytical chemist
Posts: 7463 Joined: 21-May-2008 Last visit: 03-Mar-2024 Location: the lab
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SAM is only a cofactor, and is not specific to INMT. It likely has a role in post-translational modification as well. "Nothing is true, everything is permitted." ~ hassan i sabbah
"Experiments are the only means of attaining knowledge at our disposal. The rest is poetry, imagination." -Max Planck
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DMT-Nexus member
Posts: 2889 Joined: 31-Oct-2014 Last visit: 03-Nov-2018
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benzyme wrote:SAM is only a cofactor, and is not specific to INMT. It likely has a role in post-translational modification as well. 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
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analytical chemist
Posts: 7463 Joined: 21-May-2008 Last visit: 03-Mar-2024 Location: the lab
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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. "Nothing is true, everything is permitted." ~ hassan i sabbah
"Experiments are the only means of attaining knowledge at our disposal. The rest is poetry, imagination." -Max Planck
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DMT-Nexus member
Posts: 2889 Joined: 31-Oct-2014 Last visit: 03-Nov-2018
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benzyme wrote: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.
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.... Quote:Almost forty years ago a researcher in the National institute
of Mental Health, in Maryland, discovered an enzyme in rabbit lung
that could transfer a methyl group to a tryptamine from the amino
acid donor, S-adenosyl-methione. With this system, Serotonin gave
N-methylSerotonin, N-methylSerotonin gave bufotenine, trptamine gave
N-methyltryptamine, and N-methyltryptamine gave DMT. what a fabulous black box that would make. Get two enzyme preperations, one that can methylate s-adenosyl-homocysteine to S-adenosyl-methionine and another that can regenerate s-adenosyl-homocysteine by transferring a methyl group to the available amine. Two catalysts in a chamber heated to 37°c, with a spigot adding tryptamine at the top and another releasing DMT out the bottom. That's the science, I'll leave the details to the engineers.
-shulgin; TIHKAL; DMT is everywhere chapter [
-eg
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analytical chemist
Posts: 7463 Joined: 21-May-2008 Last visit: 03-Mar-2024 Location: the lab
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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. "Nothing is true, everything is permitted." ~ hassan i sabbah
"Experiments are the only means of attaining knowledge at our disposal. The rest is poetry, imagination." -Max Planck
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DMT-Nexus member
Posts: 2889 Joined: 31-Oct-2014 Last visit: 03-Nov-2018
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benzyme wrote: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. 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-DimethyltryptamineIs this a reasonable pathway? -eg
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DMT-Nexus member
Posts: 2147 Joined: 09-May-2009 Last visit: 24-Mar-2024 Location: the shire, England
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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!"
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analytical chemist
Posts: 7463 Joined: 21-May-2008 Last visit: 03-Mar-2024 Location: the lab
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entheogenic-gnosis wrote:benzyme wrote: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. 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-DimethyltryptamineIs this a reasonable pathway? -eg 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. "Nothing is true, everything is permitted." ~ hassan i sabbah
"Experiments are the only means of attaining knowledge at our disposal. The rest is poetry, imagination." -Max Planck
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