Posted by Larry Hoover on September 10, 2004, at 9:03:49
In reply to Re: Supplements for brain fog? » Larry Hoover, posted by raybakes on September 10, 2004, at 5:02:56
> Hi Larry, I've looked up a bit more about biotpterin, thought you might be interested...
Oh, yeah. I like it when someone shows me where I'm missing pieces of the puzzle.
> >The phenylalanine hydroxylase deficiency syndrome is also know as PKU. I have never heard of an acquired form of PKU. <shrug>
>
> I think I may have a reduced function of phenylalanine hydroxylase, that may behave like PKU when I'm low in the co-factors like biopterin and NADPH - here's some abstracts that may explain..How do you respond to tyrosine? The very same cofactors apply there, as well.
> Depression and biopterin
>
> Mental illness in mild PKU responds to biopterin
> http://www.bh4.org/pdf/koch.pdf
>
> Biopterin responsive phenylalanine hydroxylase deficiency.
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14726806I love those "light-bulb moments". <grin> It's starting to make sense to me, why some people respond better to 5-HTP than to trytophan. They're already past the hydroxylase "bottleneck". I didn't even know there was such an enzymatic restriction, even in theory. Thing is, if they respond to 5-HTP, they may also need l-DOPA, to get past the corresponding tyrosine hydroxylase inefficiency.
http://jms.ndmctsgh.edu.tw/PDF/2203095.pdf
If you paste the title of the following into google, and search with the quotation marks, you'll come to a full-text link (registration required, but free):
FACTA UNIVERSITATIS
Series: Medicine and Biology Vol.11, No 2, 2004, pp. 49 - 54 UC 577+61BIOCHEMICAL FUNCTIONS AND CLINICAL IMPORTANCE OF UNCONJUGATED PTERIDINES
Gordana Bjelaković1, Tatjana Jevtović-Stoimenov1, Bojko Bjelaković2, Ivana Stojanović1 1Institute of Biochemistry, Faculty of Medicine, University of Niš 2Clinic of Pediatrics, Faculty of Medicine, University of Niš, Serbia and Montenegro
Summary. Tetrahydrobiopterine (BH4) and its relatives are classified as unconjugated pteridines or pterins distinguishing them from the folates. BH4 is not a vitamin for mammals, since they can synthesize it. GTP is the major precursor of atoms in the pterin nucleus. The initial step in this pathway is conversion of GTP to D-erythro-7, 8-dihydroneopterin triphosphate, a reaction catalyzed by the enzyme GTP-cyclohydrolase I (EC 3.5.4.16; GTP-CH). There are many important metabolic functions of BH4: it is a crucial cofactor in hydroxylation reactions of phenylalanine, tyrosine and tryptophane. The finding of BH4 participation in monoaminergic neurotransmitter metabolism regulation contributed to the knowledge of atipic neurological symptoms in some kinds of "phenylketonuric" children. As a cofactor of nitric oxide syntheses BH4 is a crucial metabolite involved in physiological function of cardiovascular system. The literature data confirm that the BH4 depletion is crucial in the control of both NO and superoxide generation (H2O2), synthesized by endothelial NOS isoforms, and consequently the formation of cell toxic peroxynitrite (ONOO −). Relationships between biosynthesis of BH4 and guanine nucleotide regulatory proteins (G proteins) or GTP-binding proteins taking part in protein synthesis has to be explained. The idea that all oxidases using molecular oxygen and producing H2O2 need BH4 appears rather relevant and it may explain more successfully the polyamine oxidase activity (PAO) in the regulation of polyamine metabolism.
> >Folate is a pro-cofactor. Folate is inactive. It is modified by various enzymes to produce activated forms, including biopterins and MTHF. Defects in the activating enzymes lead to functional defects in folate metabolism which are not ameliorated by folate supplementation.
>
> Not sure about folate being a substrate for biopterin - I heard several people say it is, but some articles say it's synthesized from GTP....
>
> 'An enzyme (dihydrobiopterin synthetase), involved in the synthesis of pterins from GTP has been implicated in this disorder (see Fig. 3). [Note that, in contrast to similar coenzymes (flavins and folates), biopterin can be synthesized by humans and is, therefore, not derived from a vitamin.]'Quite correct, upon closer examination. There was once thought to be an interchange between these two systems, probably because folate can serve as a less efficient cofactor for e.g. NO-synthase. It was believed that shunting between folate and H4-biopterin must be taking place. I see that is not the case. The death of another factoid. (Factoid was coined by a friend of mine, to describe a factual truth assumed by most people, which upon closer examination, does not stand up to scrutiny.)
> >I see no mention of selenium. It's a pretty important part of quenching this free-radical cascade.
>
> I do take selenium in thiodox from allergy research - it has both riboflavin and selenium to help reduce glutathione - I don't seem to do that well with selenium alone.
>
> Thanks,
>
> RayOK, the problem I see with biopterin defects (two real possibilities, one in de novo synthesis, the other in recycling of H2B back to H4B), is that H4B is both very poorly absorbed from the gut (some estimates at about 12%), and does not readily cross the blood-brain barrier. Methinks that one of my own responsivities to supps, that of Enada NADH, is that it may not only re-energize my ailing mitochondria, but it may also give my H2B --> H4B recycling a major boost. If so, then neurotransmitter precursor loading with NADH might be an effective augment. Experiment requires purchase of supps, though.
Thanks for joining our little world, dude. Brains tend to work in synergy (sum greater than the parts), IMHO.
Lar
poster:Larry Hoover
thread:359642
URL: http://www.dr-bob.org/babble/alter/20040901/msgs/389122.html