To those it might concern I thought I’d share this letter to a
colleague that’s been edited and corrected of gross errors.
I’d like to take this opportunity to apologize to the faithful
who have had to put up with the piss poor editing I’ve been
producing of late. My system’s been down for a long time and I’m
I’m not quite literate yet. I’m still getting over the nightmare
of restoring both computer and net access from scratch. Gee, maybe
my phone system will be working again soon also… thanks for your
patience. I really appreciate it.
A colleague asked:
> What compounds are you using as pro-coumarins? I wasn’t aware that
> the body was able to make coumarins. Can it?
The immediate precursors are dihydroxy, and dihydroxymethoxy cinnamic
acids. However, these are fairly labile and not readily produced on a
kilogram scale. I’m using pro-scopoletin and umbelliferone moieties
from a little further upstream. These trace human metabolites of
phenylalanine are ubiquitous in food and medicinal plants and readily
produced chemically on megakilo scales. I’ve successfully compounded
tablets of elegance that are acid buffered for maximum absorption, etc.
I’m just a little short on my application fee for the health department
inspection, labels, etc. Start-up capital is always a bitch!
My formulation is proprietary until limited trial in advanced ovarian
carcinoma and an advanced case of AIDS produces confirmation of the
dosage schedule, etc. However, I could always use a skilled partner.
What are you doing for the rest of your life? If you have any patients
in critical need let me know.
Yes, umbelliferone and scopoletin are both trace metabolites in
man. Umbelliferone is increased in PKU, however, scopoletin is in
a little different pathway. These two compounds represent the last
two rungs of the oxidative ladder that modulates the GGT’s and all
the function and structure that evolves from these primary enzymes.
This paired set of coumarins are the Ying and Yang of cell physiology.
Both are antitumor and anti-viral. However, being active and at the
end of the chain they are quickly (very) conjugated and excreted.
(fluorescing a beautiful blue as they go… The immediate scopoletin
precursor fluoresces green)
I get a kick out of the scopoletin system because its found
in tobacco right next to the carcinogenic system of benzenoid cpds.
In fact, in plant viral and fungal attack, after leaching out the
chlorophylls, you can see halos of blue fluorescence around all the
sites of necrosis. (scopoletin and its precursors to the rescue) It
actually stops disease progression.
As we’ve discussed before, the problem in man has been the extremely
short sero-lifespan of exogenous coumarins despite the great in vitro
anti-cancer/antiviral effects, and the sporatic miraculous remissions
in vivo.
However, when I found precursors appearing in normal urine largely
unconjugated I became excited. When I found the precursors
demonstrating the same type of tissue transglutaminase modulation
after strong hormonal flux in putative plant membrane GGT’s, I became
overjoyed.
These guys are dirt cheap and non-toxic.
All of this information has been known to some degree in the literature.
It just has been obscure and unrelated. I guess that’s why God made
little pantherapeuticologists…
Theoretically its interesting to be able to explain spontaneous
remissions without thinking the immune system somehow just starts
functioning more efficiently, or suddenly recognizes there’s a problem.
Biochemically we can readily postulate about variations in precursor
production, rates of conjugation, etc. Statistically it would hold up.
The extremely elegant immune system suddenly fixing itself after six
months of tumor growth never has set right in my mind.
The Japanese recently have used oxidative systems to produce 3-hydroxy-
coumarins. These show even stronger enzymatic inhibition, e.g.
lipoxygenase, etc. However, I think they’ve missed the boat in terms
of what is normal physiology and how to modulate it to maintain health
and correct pathology. Everybody’s just looking for new classes of
drugs to produce.
The body produces them just fine- just not fast enough to keep up with
the firestorm of retroviral invasion, or the neoplastic nightmare of the
vicious biofeedback loop occurring in carcinogenesis. So, we give a
little supplementation.
The problem is always easy once the solution is known.
I appreciate your thoughts and criticisms.
Thanks,
Charlie