Name That Metabolite!

A guided tour through the metabolome

Excerpt: "4. WHAT IF I CAN’T IDENTIFY A METABOLITE?

Join the club. Few metabolites in metabolomics data sets correspond to the “canonical” biochemical pathways found in textbooks, Patti says, and many have never been seen before. This, combined with the fact that metabolites, unlike proteins, do not assemble from a small number of known and easily differentiated building blocks, means researchers can rarely name every molecule they see."

My comment: Obviously, this is a problem for anyone willing to attempt to isolate a nutrient-dependent human pheromone (i.e., a molecule from a mixture of species-specific pheromones: the metabolites of nutrients that control reproduction in species from microbes to man). However, pheromones have been isolated in some species, which means that despite our omnivorous diet and the complexities of our microbe-dependent metabolome, someone will isolate a human pheromone from a mixture like the androstenol/androsterone mixture that appears to epigenetically affect women's behavior. This should happen soon.

From the time the term pheromones was defined in 1959, it took until earlier this year to find extraordinary proof of a moth pheromone that controls reproduction. However, some advances like this have been quickly made because they are based on what has been learned about molecular epigenetics and conserved molecular mechanisms across species.

Unfortunately, even though we know that the molecular mechanisms of pheromone production are nutrient-dependent in species from microbes to man, this moth pheromone reportedly resulted from a "mutation." That misrepresentation of cause and effect might lead some people to believe that pheromonal communication in ~ 180 000 species of moth and butterfly in the world is due to ~180,000 different mutations. They are likely to think that mutations resulted in species-specific changes in pheromones, because small differences in different moth 'scents' enable the males to find females of their own species. In the case reported, it was a small difference caused by substitution of one critical amino acid. How did this substitution become misrepresented as if it were a mutation? I don't know.

However, I know this erroneous report of mutational cause can be placed into the perspective of Darwin's 'conditions of life.' Indeed, we can be sure that the adaptive evolution of each species required nutrients -- food to sustain life (sans mutations). We can also be sure that the metabolism of nutrients to pheromones, which control reproduction, occurred sans mutations so that the existing supply of nutrients was not exhausted by mutants.

Besides, placed into the context above, a species of mutant moths could not survive if members of the species could not identify each other as nutrient-dependent reproductively fit conspecifics. Thus, if a mutation caused the reported substitution of one critical amino acid, the mutation would also have had to simultaneously occur in both males and females of the species so that they could identify a reproductively fit mate. However, the sex differences in the moths that enable them to recognize the difference between males and females also would have had to be physiologically effected by the mutation. (The mutation would have to cause sex differences in hormone-dependent organization and activation of behavior).

The entirety of the mutation-driven scenario involving substitution of one critical amino acid seems unlikely, but even more so due to examples in other species that link nutrients, but not mutations, to differences in pheromone production. I've detailed those examples in a recent review, and included one from additional studies at Harvard that report their findings in vague terms of mutation-driven evolution in a human population.

My review includes a detailed model of epigenetic effects. The changes in the human population, which are associated with the change in physical features that are species-specific and sexually selected , are nutrient-dependent and pheromone-controlled. That's consistent with what we have learned from examples of across species comparisons. Mutations theory is not!

See also: Microbes can influence evolution of their hosts. To demonstrate this in invertebrates (i.e., insects), they used three species of Nasonia (wasps). Their results clearly indicate that the microbiome influences adaptive evolution sans random mutations via the microbial metabolism of nutrients to pheromones that control reproduction -- as noted in Nutrient-dependent/pheromone-controlled adaptive evolution: a model with the following citation: Niehuis, O., Buellesbach, J., Gibson, J. D., Pothmann, D., Hanner, C., Mutti, N. S., et al. (2013). Behavioural and genetic analyses of Nasonia shed light on the evolution of sex pheromones. Nature, 494, 345–348.

Links to cited works are available from my domain.

Just to make sure I understand what you're saying....

(07-29-2013 11:06 AM)jvkohl Wrote:  a nutrient-dependent human pheromone (i.e., a molecule from a mixture of species-specific pheromones: the metabolites of nutrients that control reproduction in species from microbes to man)

I don't understand why species specificity is an issue with pheromones. The point is supposed to be that pheromones, by definition, are an intra-specific signal, not a species specific signal. Right? Androstenone and androstenol works for boars and for humans and are still popularly considered to be pheromones. It doesn't matter if they're species specific because they signal within a species.

And even that seems problematic. Why can't some organisms communicate cross-species via hormones/pheromones. i.e. auxins in animal urine function as growth promoters in plants.

I can understand that pheromones are typically either pro-hormones, hormones, or metabolites of hormones, (or sometimes analagous molecules from the autocrine or paracrine systems, perhaps?)

"Nutrient dependant" seems an overly general descriptor, though, since there are many nutrient metabolites that we don't expect to function as pheromones because they aren't related to the body's chemical signals.

Sorry if any of that was badly worded. I'm in a rush right now.

Androstenol works in women probably because it alters levels of luteinizing hormone. Androstenone does not work probably because it is not species specific and it is not typically considered to have a pleasant odor.

Androsterone works in combination with androstenol, as we have shown in two studies, probably because androsterone is more specific to primate metabolism and in drug testing for doping in athletes it is a measure of what probably translates to an indicator of reproductive fitness.

Hope that helps.

(07-29-2013 7:12 PM)jvkohl Wrote:  Androstenol works in women probably because it alters levels of luteinizing hormone. Androstenone does not work probably because it is not species specific and it is not typically considered to have a pleasant odor.

Androsterone works in combination with androstenol, as we have shown in two studies, probably because androsterone is more specific to primate metabolism and in drug testing for doping in athletes it is a measure of what probably translates to an indicator of reproductive fitness.

Hope that helps.

The Pheromone Androstenol (5α-Androst-16-en-3α-ol) Is a Neurosteroid Positive Modulator of GABAA Receptors

http://jpet.aspetjournals.org/content/31...4.abstract

I think you'll find a lot of folks on these forums who will disagree with androstenone "not working." At least in particular situations.

But my point is, in part, that pheromones as we know them don't need to be species specific. If you argue against that by saying "It doesn't work because it's not species specific" you're assuming what you're trying to prove. (i.e. that effective chemosignals are species specific.)

(07-29-2013 10:29 PM)wiserd Wrote:  The Pheromone Androstenol (5α-Androst-16-en-3α-ol) Is a Neurosteroid Positive Modulator of GABAA Receptors

http://jpet.aspetjournals.org/content/31...4.abstract

I think you'll find a lot of folks on these forums who will disagree with androstenone "not working." At least in particular situations.

But my point is, in part, that pheromones as we know them don't need to be species specific. If you argue against that by saying "It doesn't work because it's not species specific" you're assuming what you're trying to prove. (i.e. that effective chemosignals are species specific.)

Thanks for your comment.
I can't argue against what works for some people in some circumstances, since the power of suggestion is exceptional, and virtually the entire concept of human pheromones started with the suggestion of androstenone as a human pheromone.

I can argue for the species-specificity because that was included in the definition of pheromones (in 1959) that has since been bandied about, as people move further and further away from scientific facts.

Can you point out a guide to pheromone types for the parchment-challenged?