Posted by Larry Hoover on June 21, 2004, at 11:50:03
In reply to Re: Pyroluria: Larry H., chemist, anyone...any help? » Simus, posted by chemist on June 21, 2004, at 8:16:57
I fear you may have stepped a little outside your "comfort zone" on this topic....
> hello there, chemist here.....this one threw me for a loop! i couldn't even find the word ``pyroluria'' in my merck manual, my taber's, even voet and voet on the off-chance, and even checked my webster's. doesn't even make an appearance in goodwin and jamison, although that is the definitive text for manic depression....so i hit pubmed - what else to do - and got 2 hits: number one is entitled ``Pyroluria: a poor marker in chronic schizophrenia,'' Am. J. Psychiatry 135:1239-1240 (1976), no abstact, and i'm not heading down to the library for this one. the second hit is more informative, ``A new prostaglandin disturbance syndrome in schizophrenia,'' Med Hypotheses 19:333-338 (1986) where the hypotheses that some schizophrenics are deficient in an enzyme called delta^{6} desaturase. as the name implies, desaturases take saturated fatty acids and desaturate (i.e., induce the formation of a double bond where there was formerly a single bond) the fatty acids. the designation omega-6 and omega-3 refers to the position of the double bond.
Of one particular double-bond, counted from the methyl terminus. The omega-count (omega being the last letter in the Greek alphabet) is the only exception I can think of which increases towards the functional group. Omega is the "inverse", sort of, of the alpha beta gamma designation.
> so, if you are lacking in the delta^{6} desaturase, you have elevated levels of omega-3 c.f omega-6,
Delta-6 is not the same bond as omega-6. In fact, the actual bond affected depends on intermediate bonds in the molecule. Delta-6 desaturase deficiency prevents the conversion of cis-linoleic acid (18:2, omega-6) to gamma-linolenic acid (18:3, omega-6). GLA is a precursor to arichidonic acid (20:4, omega-6) via dihomogamma-linolenic acid (18:4, omega-6).
Omega-3 fatty acids have higher affinity for the normal d-6-d enzyme, but the deficiencies conferred by defective d-6-d are modulated by dietary factors.
> which in turn leads (to among other things) to an important precursor for arachadonic acid, which in turn goes to things that help relieve pain, etc. (the stuff in question is cis-linoleic acid).
Arichidonic acid goes to pro-inflammatory prostaglandins. Pain relief comes from omega-3 products, or an alternate pathway that arises from GLA.
> now, pyroluria is the opposite, but the one abstract i am reading indicates that elevated cic-linoleic levels are not due to mutant delta^{6} desaturase, but to something else.
Now, that has me interested. What something else?
> so, fasting insulin levels get higher, and some compound they refer to as a urinary kryptopyrolle shows up.
Arising from disturbances in heme homeostasis.
> the part that interests me is that this condition has either been renamed or dismissed as being something that can be addressed with proper omega-3/omega-6 supplementation or ruling out diabetes (i'm uessing mellitus).
There is substantial evidence that the increase in many health problems today are due to poly-unsaturated fatty acid deficiencies, but particularly those in the omega-3 class. The historical dietary ratio (pre-agriculture) of omega-6: omega-3 was likely about 1:1. It is currently estimated at anywhere between 30:1 and 200:1, primarily due to the intake of vegetable oils.
> heck, it's not even in the DSM-IV TR. maybe i'm looking in the wrong places, but it sounds like this could have been a medical hypothesis that didn't make the grade....in any event, i wish you well, and hope this helps (i sure learned a lot!)....all the best, chemist
That's what I love about questions. Keep 'em coming!
Lar
poster:Larry Hoover
thread:358464
URL: http://www.dr-bob.org/babble/alter/20040613/msgs/358602.html