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Amino-Alkaloids of Sacred Cacti

Isanara

Ponderer
I read a paper the other day claiming that the biological role of mescaline and other related alkaloids is unknown.

Why would an organism devote energy to producing and storing these molecules in such significant amounts?

I believe I have a perspective and an explanation that might be of interest to some here.

Lets start with Tyramine, a well known alkaloid:

Tyramine.svg.png

It's a hydroxylated phenolic with an amine.
That's easy enough to see.

What about if we methylate that amine?
We call that Hordenine or dimethyltyramine:
Dimethyltyramine.svg.png


It's an N methylated Tyramine, just like the name suggests.

Well, what if we add more to this?
Why not hydroxylate and methylate it a bit more?
Here we have an example of that:
3-Methoxytyramine.svg.png


This tyramine molecule has a methoxy group on the 3 position of the molecule!
That's probably why it is called 3-methoxy-tyramine.

In order to do this the organism first adds a hydroxl group to the phenolic ring and then that is O-methylated by a methyltransferase.


In fact, if we do this to the 3, the 4 and the 5 position of the molecule we get 3,4,5-Trimethoxy-Phenyl-ethyl-amine, emphasis on the structural components of PEA being mine. Phenyethylamine or PEA is basically tyramine without any hydroxylation. PEA can be described as being composed of a phenolic group, an ethyl group and an amine.

This is it:

Phenethylamine2DCSD.svg.png


In fact, for cactus alkaloids it is obvious that they proceed from tyramine to other forms, via hydroxylation and methylation specifically.
Something else is worth noticing here.

It has to do with the observations about alkaloid production.
You see, in numerous studies, tests and anecdotes alkaloid+ cacti have specific patterns of alkaloid production and distribution.
Take the dark treatment of cacti, like San Pedro as an example.
The prolonged dark period causes alkaloids to gradually increase and then after the darkness continues they then decrease.

In Peyote studies something similar happens. Drought causes the alkaloids to increase and then after watering the plants the alkaloids then decrease.

In peyote this coincides with a flush of flowers and fruit.


In plants exposed to darkness, after a time, there is an up-regulation of genes associated with the degradation of chlorophyll.
That is to say, plants activity break down their chlorophyl and this allows them to use the materials it is made from elsewhere.
However, alkaloids made do not just stick around, in peyote after watering the amount decreases and in San Pedro in the dark the alkaloids also eventually decrease.
This is potent evidence that the alkaloids are being metabolized and used as sources of energy and molecular feedstock.

There is an indication that methylation and hydroxylation of alkaloids allows plants to store Nitrogen, Oxygen, Carbon and Hydrogen. Essentially by adding and removing hydroxyls and methyl groups a plant can take the same basic subunits that sugar is made from and store them in a form that allows it to be used by the plant, but which prevents that stored energy from being exploited by other organisms. The biology of peyote, where flushes of growth correspond to a decrease in alkaloids make it quite clear that alkaloids are being used as energy and molecular storage methods. This appears to work by hydroxylation and methylation, which appear to be reversible, otherwise alkaloids would never decrease or dissapear once formed. They are not permanent molecules and there is evidence they are also actively transported by plants to tissues with metabolic activity, and that the alkaloids help buffer the CAM acids, which are also formed from the same basic components of carbon, oxygen and hydrogen.

The origin of PEA alkaloids predates the origin of plants and several of the roles that the alkaloids can serve in biology relate to this. Many of them can interfere with cellular processes, this allows them to be energy storage mechanisms that offer protection against ingestion and infection by microbes, fungi, viruses and animals. However no actual selective pressure exists in nature that specifically selects for mescaline over other variations of the molecule, like Pellotine.

Pellotine:
Pellotin_Structural_Formula_V1.svg.png
Note that Pellotine has cycled from a PEA to an Isoquinoline via ring closure at the amine, but it is just another collection of methyl and hydroxyl groups on a tyramine skeleton.

This is where things get interesting, as that cacti exist in which mescaline is the dominant alkaloid. In fact as a trace alkaloid mescaline is widespread throughout cacti, but as the primary component of an alkaloid+ cactus it is known only from San Pedro cacti and then only from specific populations, specimens and cases, for many San Pedro cacti contain little to no mescaline or contain modest amounts but have other alkaloids present as the dominant alkaloid.

I am focusing on PEA alkaloids here, but the Tryptamine alkaloids are quite similar in many ways, I may get to them, perhaps not anytime soon.

Alkaloids in cacti allow them to accumulate and store molecular energy in a form resistant to attack. This proceeds by stepwise hydroxylation and methylation and is known to be promoted by conditions known to degrade chlorophyl. The cacti then metabolize this stored energy for growth and reproduction. Many different molecular variations can facilitate this and mescaline is but one of them.

This is a work in progress that I will revise as needed.
 
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Here is the structure of chlorophyll-a, note that it contains carbon, hydrogen, oxygen, nitrogen and magnesium:chlorophyll01-3267874733.png

And here is the structure of sucrose, a major sugar in plants, note that it contains oxygen, carbon and hydrogen.
image-5-sucrose-185326129.jpg


The tyramine skeleton allows the storage of hydrogen, carbon and oxygen, the components sugar is made from, in a form that cacti can use, but which other organisms find potentially complicated to exploit.

In nature as well, in various conditions of stress chlorophyll can break down. Note that it is also loaded with oxygen molecules. This means that chlorophyll can produce problematic molecules called reactive oxygen species or ROS. These oxygen radicals are known to damage other molecules. Cacti, in having a way to store the components of chlorophyll can limit production of harmful and reactive reactive oxygen species by storing the oxygen away in a manner that keeps it stable and prevents it from damaging other molecules. This is because alkaloids like mescaline are far more stable than chlorophyll is.
Each molecule of mescaline can store three molecules of oxygen, as well as a molecule of nitrogen. Under conditions which are likely to cause the breakdown of chlorophyll, alkaloid+ cacti frequently produce alkaloids and then when conditions improve they then convert the alkaloids back into other less stable products like chlorophyll. However if conditions do not improve the cacti eventually exhaust their alkaloid supply in a last effort to endure and eventually die.

More later.
 
This is the structure of malic acid:


Äpfelsäure3.svg (2).png
It has oxygen, carbon and hydrogen, which in addition to nitrogen also form the basis of tyramine alkaloids, including but not limited to mescaline.
Malic acid can be used as an energy source by many types of microbial life. That is to say that many fungi and bacteria love to eat it.

By breaking malic acid down into methyl and hydroxyl units and by placing them on a tyramine skeleton, organisms can store carbon and oxygen in a stable form that buffers against CAM acids and which fungi and bacteria cannot eat as an energy source.

Mescaline is found in a malate salt form in cacti, for example. In adverse conditions which limit normal metabolism but which do not prevent cellular activity the CAM acids build up and the chlorophyll breaks down. Both of these situations present challenges for an organism and the solution to these issues is found in the use of alkaloids as pH buffering antimicrobial storage molecules that can be assembled and disassembled as needed to supply the plant with the parts and energy required to thrive, as well as to recover from periods of extended stress where ordinary metabolism is not possible.

Because of human interactions with cacti and their alkaloids we tend to view mescaline as distinct, but our blood brain barrier essentially filters out most of the other tyramine alkaloids, even mescaline itself appears to cross this barrier poorly, requiring high doses of the alkaloid to allow enough of it to reach the brain for psychedelic effects. However in terms of cactus biology it appears that mescaline is not particularly special nor distinct among the PEA alkaloids. The exception to this is found in the use of cacti by humanity.

Humans appear to be the only extant selective pressure on cacti for the production of mescaline. In fact some forms of San Pedro appear to be domesticated. Some even appear to have been domesticated and then appear to have gone feral or are in the process of doing just that. That, however, is another related topic, the origin and evolution of San Pedro cacti.

More later.
 

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From: The biosynthetic pathway of the hallucinogen mescaline and its heterologous reconstruction https://www.sciencedirect.com/science/article/abs/pii/S1674205224001795


Notably, we identified a novel CYP76AD enzyme, which, to the best of our knowledge, is the first tyramine hydroxylase identified from plants. We also identified two groups of regiospecific OMTs and a highly similar methyltransferase (MT) ortholog capable of non-specifically N-methylating all the phenethyl intermediates within this pathway.

This study identified related but distinct sets of methyltransferase enzymes and a hydroxylase enzyme. This appears to involve a coded enzyme corresponding to a specific allele and is likely conserved and found in other cacti.

This indicates that in the case of Trichocereus as well, the distinct sets of enzymes that result in a given alkaloid are allele specific. Thus the N-methyltransferase of T. terscheckii, which methylates the amine, is related to but distinct from the methyltransferase enzyme which methylates the hydroxyl groups attached to tyramine by the hydroxylase enzyme, which also has its own allele.

Each enzyme having its own allele, it is possible for a single species population to have specimens with distinct chemical differences. An example is the study of T. terscheckii that found some specimens with trichocereine by itself, some specimens with mescaline by itself and some specimens with both alkaloids present.

This is a potentially useful aspect to consider in the breeding of the plants as well as in regard to their natural history. Essentially, in San Pedro cacti, different combinations of alleles for enzymes can result in different alkaloids and mixtures of them.
 
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A lot here! And very interesting ideas. I'm not a chemist (more a philosopher) so will have to read and chew on this some, but thank you for sharing your ideas about this mysterious topic with so much effort and detail.

One love
 
From: The biosynthetic pathway of the hallucinogen mescaline and its heterologous reconstruction https://www.sciencedirect.com/science/article/abs/pii/S1674205224001795




This study identified related but distinct sets of methyltransferase enzymes and a hydroxylase enzyme. This appears to involve a coded enzyme corresponding to a specific allele and is likely conserved and found in other cacti.

This indicates that in the case of Trichocereus as well, the distinct sets of enzymes that result in a given alkaloid are allele specific. Thus the N-methyltransferase of T. terscheckii, which methylates the amine, is related to but distinct from the methyltransferase enzyme which methylates the hydroxyl groups attached to tyramine by the hydroxylase enzyme, which also has its own allee.

Each enzyme having its own allele, it is possible for a single species population to have specimens with distinct chemical differences. An example is the study of T. terscheckii that found some specimens with trichocereine by itself, some specimens with mescaline by itself and some specimens with both alkaloids present.

This is a potentially useful aspect to consider in the breeding of the plants as well as in regard to their natural history. Essentially, in San Pedro cacti, different combinations of alleles for enzymes can result in different alkaloids and mixtures of them.
Nice reference - Molecular Plant has some fascinating stuff going on.

Molecular Plant

Volume 17, Issue 7, 1 July 2024, Pages 1129-1150

Abstract

Mescaline, among the earliest identified natural hallucinogens, holds great potential in psychotherapy treatment. Nonetheless, despite the existence of a postulated biosynthetic pathway for more than half a century, the specific enzymes involved in this process are yet to be identified. In this study, we investigated the cactus Lophophora williamsii (Peyote), the largest known natural producer of the phenethylamine mescaline. We employed a multi-faceted approach, combining de novo whole-genome and transcriptome sequencing with comprehensive chemical profiling, enzymatic assays, molecular modeling, and pathway engineering for pathway elucidation. We identified four groups of enzymes responsible for the six catalytic steps in the mescaline biosynthetic pathway, and an N-methyltransferase enzyme that N-methylates all phenethylamine intermediates, likely modulating mescaline levels in Peyote. Finally, we reconstructed the mescaline biosynthetic pathway in both Nicotiana benthamiana plants and yeast cells, providing novel insights into several challenges hindering complete heterologous mescaline production. Taken together, our study opens up avenues for exploration of sustainable production approaches and responsible utilization of mescaline, safeguarding this valuable natural resource for future generations


I'd contend against your hypothesis that cacti are using mescaline as food store, though. It would be worth checking to see whether 3,4,5-trimethoxyphenylacetic acid possesses any auxin-like activity, I feel. One more thing about mescaline is that it's quite strongly basic which seems to assist acid accumulation during the CAM dark phase. In that sense it assists the plant in accumulating metabolic feedstock, which is kind of a metaversion of the food storage idea.

The argument around CHON sounds a bit grade-schooly to me if I'm going to be brutally honest. All living organisms rely on those macroelements so it doesn't strike me as remotely ground-breaking nor even particularly useful, especially considering the major energy storage systems in plants are carbohydrates, and additionally lipids in the case of seeds. To be generous, there could be a case for it being a nitrogen storage method with a few bonus functions, so it's definitely something worth pondering more deeply.

One study suggests that it serves as an insect antifeedant as well, by acting on the insect CNS. There's a reference around here somewhere (relating to a spurious claim of TMA occurrence in T. terscheckii, much as I recall) but it's a bit late in the day for me to go about digging that one up.

I hope you'll be making good use of the existing resources on the forum as there are a good few gems of knowledge hidden amongst the discussions here that will very likely provide ample food for thought.

Looking forward to your further contributions!
 
To be generous, there could be a case for it being a nitrogen storage method with a few bonus functions, so it's definitely something worth pondering more deeply.
As far as I know one of the recognized "functions" of alkaloids and protoalkaloids is nitrogen storage, even if they're not the main reservoir. In the dark the synthesis of Rubisco and other photosynthetic proteins, that in normal conditions take up a significant portion of nitrogen, decreases, so a part of nitrogen could be reallocated to other biosynthetic pathways.
Besides helping against biotic stresses as you said. But this doesn't seem to explain the increase and decrease in the synthesis of these protoalkaloids according to varying environmental conditions. Either they are helpful against abiotic stresses as well, in ways we don't yet know, or their biosynthesis is promoted by the same signalling pathways activated by abiotic stresses.
 
One more thing about mescaline is that it's quite strongly basic which seems to assist acid accumulation during the CAM dark phase. In that sense it assists the plant in accumulating metabolic feedstock, which is kind of a metaversion of the food storage idea...


One study suggests that it serves as an insect antifeedant as well, by acting on the insect CNS. There's a reference around here somewhere (relating to a spurious claim of TMA occurrence in T. terscheckii, much as I recall) but it's a bit late in the day for me to go about digging that one up.

I hope you'll be making good use of the existing resources on the forum as there are a good few gems of knowledge hidden amongst the discussions here that will very likely provide ample food for thought.

Looking forward to your further contributions!
Note that I mentioned the pH buffering effect.

I also mentioned that PEA alkaloids predate plants, I didn't mention this specifically, but they predate insects as well.

The TMA conflation for T. terscheckii was discussed well enough at the old forum. Trout had some interesting comments there if I recall correctly.

Mescaline and related molecules can act as spindle inhibitors during mitosis. This results in pronounced antiviral and antimicrobial effects. Many of these inhibitory effects on cellular processes appear to relate to functions from a time before multicellular life existed, but after the emergence of eukaryotic cellular life. These amino-alkaloids are highly conserved across numerous domains and kingdoms and are nearly as ubiquitous as methylation itself, which occurs in all known forms of life.

In studies of location and active transportation of mescaline in non-stressed actively growing San Pedro, it was found associated with active metabolism, older flesh that was not in a state of active metabolism had far lower levels of alkaloid. It was clear that the plant was richest in alkaloid in the areas of the plant that exhibited active photosynthesis. This indicates that alkaloid is involved in metabolic turnover.


More later.
 
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A few things to consider:

1:

The dominant alkaloid is likely to represent a methylated tyramine. This includes numerous forms of methylation and even reversible cycling into methylated isoquinoline. As an energy storage mechanism the fully methylated form of the molecule should be the most abundant of them.

2:

The scaffold molecule or starting point will be present only in very low amounts, as that it is rapidly processed by further methylation and hydroxylation.

3:

Slight variation in methylation and hydroxylation results in trace amounts of other molecular variants aside from the alkaloids of the primary pathway.

4:

The most advantageous situation for the plant is to have stores of the fully methylated alkaloid, as well as minor portion of related alkaloid that has been demethylated by metabolic processes. This is as opposed to having mostly carbon and oxygen depleted molecules.

This means that at a given time a portion of the total alkaloids should be partially de-methylated and or de-hydroxylated forms of the predominant alkaloid, that are stages in a series of methylations and hydroxylations, that are only a couple of enzymatic steps from the dominant alkaloid.

5:

It is not always advantagous to fully demethylate a molecule, removing only one or two methyl groups at a time for use is more practical than completely dissembling the molecule.

This means it is more likely that the working demethylated versions of the molecules can vary, but will predominantly be a set and ratio of molecules like DMPEAs and mescaline, which are only one or two steps apart, rather than say... tyramine and mescaline, which are many more steps apart.

6:

At times of stress, when metabolism of stored carbon isn't an option a plant will, if it has the resources and energy, store large amounts of the dominant fully methylated molecule, which promotes survival, both as an energy resource and as a protective chemical. Naturally each molecule of alkaloid requires a single nitrogen. A more well fed plant has more potential to produce alkaloid in a stressful situation than a poorly fed one. There is a stoichiometric reason for this.

7:

If and when alkaloids are made to balance out malic acid production from CAM metabolism, it is unlikely that a plant would remove the malic acid from the alkaloid salt and leave the alkaloid in a basic form. Basic forms of tyramines have never been found in cacti, just malate salts. This strongly indicates that the alkaloid is being metabolized in some way otherwise as acids are used up freebase alkaloids would occur. And notably carbon, oxygen and hydrogen which form the methoxy groups of various common cactus tyramines are the same molecules that malic acid is made from. This indicates that alkaloid methoxy groups can, in all likelihood, be transformed back into malic acid, and that malic acid can be broken down and stored this way.

Alkaloids do not just accumulate thus they cannot be an end product or the final product of a pathway, but they are often highly stable as well, making them excellent storage molecules.

8:

PEA alkaloids do not just accumulate, they appear to cycle. This includes daily as well as seasonal cycles, as well as in relation to cycles of reproduction and maturity. Because they cycle in relation to known metabolic cycles and are known to be associated with active metabolism and photosynthesis, as well as stress response, and yet do not accumulate, we can infer that they are actively metabolized. We also find them in ratios in stages of a series of methylations which supports this. We do not find them incorporated into other tissues or exuded from the organisms, the components alkaloids are made of are simple building blocks common to most life, like phenolic subunits, amines, oxygen and hydrocarbons. It is tenable to assume that they function largely as molecular storage mechanisms with protective properties.

Reversible methylation is also widespread in cellular life.


Ancient origins:

It is my belief at this time that the origin of PEA alkaloids was as variants of molecules involved in reversible methylation in primordial eukaryotic ancestors and that selectively, organisms with increased amounts of these molecules were able to benefit from their presence in multiple ways. These simple amino-alkaloids occur in algae, plants, fungi and animals. They are extremely common as trace chemicals in cells of nearly all life and there are examples of organisms with elevated levels of these molecules in nearly every family of life that exists. This indicates strongly that these molecules are extremely ancient in origin.

More later.
 
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The TMA conflation for T. terscheckii was discussed well enough at the old forum. Trout had some interesting comments there if I recall correctly
Here's the link to the same thread here on the new forum:
One of the main things I took away from it, apart from the poor interpretation of the spectra, was that it focussed on the action of cactus alkaloids on some fly or other, Drosophila buzzatii (or maybe I misremember the genus, my recollection is somewhat hazy when it comes to entomology).

I've enjoyed reading your hypothesis and the associated background information. It comes across as rather curious that you choose to focus on the points where I highlighted areas of your work that, in my view, could do with a bit of polishing up. How would you prefer me to have addressed this? What aspects of those parts of my replies would you say make them passive-aggressive. Misunderstanding may have arisen through my attempt to achieve economy of words too late at night in my time zone. Better that than unbridled yes-mannery, I'd say.
 
The premise of my concepts here is certainly simplistic, even elementary. There is room for improvement as well, in several areas. However, I am recovering from massive data loss, including a lot of images, writing and a digital library of supportive literature. I was batch resizing an image collection similar to those in the post above, but without transparency, with standard sizing and molecular representation, when I experienced my data loss.

As for the theory, I almost didn't post it anywhere at all. If it isn't welcome or is seen as something the equivalent of certain infamous waterpark-fantasies then someone should just come right out and say so.

Despite my awkward word use and the ever present reality that I could be wrong about it, partly or entirely... I may have had someone with more knowledge of cacti, chemistry and phenylethylamines than I, look over the material and post to see if i shared any glaring errors, misconceptions or clearly erroneous claims. So far so good.

I could go back, perhaps should, and explain methyl groups, cycling and several other related concepts so that someone with nearly no chemistry knowledge could read it and then understand all of the words I use and their concepts. I have an inclination to do that, as I do it in casual conversation with other people in real life. I could word things better as well. There is plenty of room for improvement, certainly. Especially in terms of making the writing more accessible to the average reader, which is ironic given the ultimate simplicity of the theory itself.

In terms of the theory, one possible origin of tyramines is as a scaffolding type molecular structure that allowed a sequential hydroxylation and then methylation, with a step of removing the methoxy group as a whole, in part of a process of metabolism in an ancient cellular organism, which was ancestral to all multicellular life. I suspect this was related to a mechanism of an active detoxification system for oxygen, which is highly reactive. The hydroxylation and methoxylation basically takes the oxygen and puts methyl groups cap right on it, sealing it, where it is remarkably stable but can still be accessed later. Early on oxygen was inherently problematic for certain organisms. Naturally I expect that this ancient organism population was marine and that in addition to being able to detox oxygen, an anti-microbial carbon storage role was also an early development, all based on a tyramine modification system.

The widespread nature of the tyramines is fascinating. We use them as signal molecules, like with the trace amine system aka the TAAR series of receptors. I suspect they are the basis of emotions, the trace amines and their receptors, I mean, in animals and their relatives. Certainly, it appears that nearly all medications that modulate emotionality affect, directly or indirectly, the trace amine system. This includes antidepressants, antipsychotic and other molecules. Interestingly, molecules like mescaline and other active amines are employed widely in low doses specifically for their ability to have positive effects upon the emotionality of the user. Microdosing of things like mescaline and psilocin has an excellent social reputation for this type of benefit.

In terms of the cacti themselves, I believe that human interactions shaped the traits of the cacti over generations and over considerable time, affecting their form and chemistry. It is my intention to address this, both in relation to this topic and as it's own topic.

If I make assumptions easily proven to be incorrect, or make a false claim about a past analysis, like the Reti et al. study for T. terscheckii which I casually referred without actually mentioning it, then I hope someone will offer a correction. I'm mistaken about a dozen things a day, but on a good day I learn about at least a couple of them and revise. If someone wants a clear reference for a specific claim, so they can see if it actually says what I portrayed then just quote the relevant part and I'll see what I can do. Challenging ideas and theories is often an excellent method of refining and improving them. I seek to be open and amenable to corrections and improvements. Note however that I consider AI and chatGPT soulless and harmful to the quality of human communication. I do not welcome advice relating to using it, other than to not.
 
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I'll need to reread this since I just gave it a quick scan. I've been diving deeper and deeper into this topic. At first I look purely at the biosynthesis route and looked for ways to increase the enzymes that are involved in those specific steps. Then I also reached the theory of alkaloids being used as mainly stress relievers where the plant mainly forms these as side-products to prevent death removing excess stressors and storing them until water/nutrients are provided to resume growth. This is the main direction I've taken and have now starting introducing the balance of plant growth hormones which is all in a flux in the plants. Cycling indeed occurs with stressful times leading to more and inverse.

MANY acids are found in plants malic, citric, oxalate and others all in a means of different pathways to preforms different functions to maintain homeostasis. pH likely has another role I've yet to dive much deeper in. Then comes the other topic of temperature where the natural habitat is constantly between 60f at night and 80s f during the day rarely surpassing this. While in most collections they go thru seasons much hotter and the influences of this since heat activates the same enzymes as drought.

I'm looking to test a theory of using these alkaloids as growth regulators to see if they help the plant better survive and deal with drought and other stresses.

I don't think the idea that many go directly to of alkaloids being 'deterrents' to animals or pests really fits or more plants would produce them if not all. Also the idea that more nitrogen should increase content doesn't fit IMO with mescaline since it is not a true alkaloids but pseudo alkaloid.
 
Also the idea that more nitrogen should increase content doesn't fit IMO with mescaline since it is not a true alkaloids but pseudo alkaloid.
Every molecule of mescaline has an atom of nitrogen.

f tyramine alkaloid, or protoalkaloid, has an atom of Nitrogen and the organism has 4-6% alkaloid on a dry weight basis where does that element come from?

If the plant isn't fed nitrogen, how is it going to make molecules that require it?
 
Every molecule of mescaline has an atom of nitrogen.

f tyramine alkaloid, or protoalkaloid, has an atom of Nitrogen and the organism has 4-6% alkaloid on a dry weight basis where does that element come from?

If the plant isn't fed nitrogen, how is it going to make molecules that require it?
doesnt directly increase content. Makes it from amino acids?
 
Every molecule of mescaline has an atom of nitrogen.

f tyramine alkaloid, or protoalkaloid, has an atom of Nitrogen and the organism has 4-6% alkaloid on a dry weight basis where does that element come from?

If the plant isn't fed nitrogen, how is it going to make molecules that require it?
We'd best not raise the spectre of Louis Kervran at this point 😁

It would, however, be hilarious if biological transmution of elements ended up getting proven courtesy of a magical cactus - I strongly doubt this would ever happen, largely on account of the way trichocereus cacti thrive on undiluted urine.
 
There is a some indication that in some cacti there are endophytes that in some cases appear to be able to fix atmospheric nitrogen. Especially with types adapted to living on rocky areas and cliffs. This includes San Pedro, generally speaking, but no specific work on their microbial symbiotes has been done that I am aware of.

I read a paper about the endophytes of a close San Pedro relative. Echinopsis chiloensis has been studied a little in that regard. It is extremely likely that San Pedro hosts similar organisms.

It can be a bit tricky, but even with plant chemistry, it helps to think in stoichiometric terms.

Mescaline is made of N, C, O and H.
Some of the enzymes used to make it likely have cofactors like copper or other elements, as well.

Trout once mentioned that near Matucana Peru, where T. peruvianus is found, copper ore is abundant. Making sure that plants have a good compliment of trace elements may also help them better produce protoalkaloids like Tyramines and Isoquinolines.

If someone was up for it, I could donate two identical clones to be grown with and without fertilizer for a couple of seasons and then a comparison could be made. I have heard anecdotes that better fed plants are stronger, but I haven't seen any data proving it.
 
There is a some indication that in some cacti there are endophytes that in some cases appear to be able to fix atmospheric nitrogen. Especially with types adapted to living on rocky areas and cliffs. This includes San Pedro, generally speaking, but no specific work on their microbial symbiotes has been done that I am aware of.

I read a paper about the endophytes of a close San Pedro relative. Echinopsis chiloensis has been studied a little in that regard. It is extremely likely that San Pedro hosts similar organisms.

It can be a bit tricky, but even with plant chemistry, it helps to think in stoichiometric terms.

Mescaline is made of N, C, O and H.
Some of the enzymes used to make it likely have cofactors like copper or other elements, as well.

Trout once mentioned that near Matucana Peru, where T. peruvianus is found, copper ore is abundant. Making sure that plants have a good compliment of trace elements may also help them better produce protoalkaloids like Tyramines and Isoquinolines.

If someone was up for it, I could donate two identical clones to be grown with and without fertilizer for a couple of seasons and then a comparison could be made. I have heard anecdotes that better fed plants are stronger, but I haven't seen any data proving it.
Very interesting - I was thinking along these lines the other day regarding symbiotic plant-plant interactions with trichocereus cacti, since many of my specimens get opportunistic volunteers appearing in their pots self-seeded from the surroundings outdoors, as well as from the compost in the case of Stachys arvensis. I very much agree that there's a great deal of potential for endophyte studies with these species. Next time I get the opportunity to examine the roots of any of my specimens, I'll be sure to look out for signs of nodule formation and the like.

Regarding trace elements, my instinct has always been to throw coinage and small pieces of jewelery into the pots, as well as sticking bird feathers into the soil as a slow-release fertiliser. It would be particularly useful to know exactly which transition elements are necessary components of the active centres of the key enzymes of the biosynthetic pathway, with a view to optimising their expression.
 
There is a some indication that in some cacti there are endophytes that in some cases appear to be able to fix atmospheric nitrogen. Especially with types adapted to living on rocky areas and cliffs. This includes San Pedro, generally speaking, but no specific work on their microbial symbiotes has been done that I am aware of.

I read a paper about the endophytes of a close San Pedro relative. Echinopsis chiloensis has been studied a little in that regard. It is extremely likely that San Pedro hosts similar organisms.

It can be a bit tricky, but even with plant chemistry, it helps to think in stoichiometric terms.

Mescaline is made of N, C, O and H.
Some of the enzymes used to make it likely have cofactors like copper or other elements, as well.

Trout once mentioned that near Matucana Peru, where T. peruvianus is found, copper ore is abundant. Making sure that plants have a good compliment of trace elements may also help them better produce protoalkaloids like Tyramines and Isoquinolines.

If someone was up for it, I could donate two identical clones to be grown with and without fertilizer for a couple of seasons and then a comparison could be made. I have heard anecdotes that better fed plants are stronger, but I haven't seen any data proving it.
The biomass of the fertilized plant would surpass any possible 'benefit' of nutrient deficiency.

I'm not very well versed but when I researched this I found C:N balance and it would remain net zero but seems to have been fazed out theory. But the amino acid metabolism still accounts for the N and plants would use it to grow along with carbon but excess Nitrogen wouldn't be used unlike with 'true' alkaloids which gain a N in the molecule as part of the C:N balance of plants
 
The meristems and areole pads also appear to host the endophytes in cacti. Also spine biology, I'll probably get to that, but am working on the art thread for now.
 
Trout once mentioned that near Matucana Peru, where T. peruvianus is found, copper ore is abundant. Making sure that plants have a good compliment of trace elements may also help them better produce protoalkaloids like Tyramines and Isoquinolines.
going along with this thinking I think a weak salt spray would prove beneficial with them getting salt breeze blown many km inland. minimal salt stress and ion exchange would help as well IMO.
 
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