Posted by Larry Hoover on December 10, 2004, at 8:39:40
In reply to Re: dopamine oxidation » Larry Hoover, posted by raybakes on November 26, 2004, at 13:00:09
> >
> > > I see the oxidative stress as the root, and acidosis as the outcome.
> > >
> > > I can go with that!
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> > So, it still is oxidative stress that needs controlling, to avoid the acidotic response.
>
> I agree, but find 'oxidative stress' too vague and feel I need to know the specific pattern of oxidative stress for each condition, and what gets oxidised!I'm a little confused by your confusion. The oxidative stress is always the same critters: superoxide anion, peroxynitrite, NO, molecular oxygen, peroxides....
What gets oxidized is either one of: antioxidant molecules like superoxide dismutase, reduced glutathione, tocopherol, ascorbate, etc. OR any other darn thing that gets in the way. Most susceptible are B vitamins followed by polyunsaturated fatty acids, thiols and sulphur bridges (sulphur moieties) and so on.
> >
> > I've been using inosine, and it certainly doesn't seem to have any adverse effects. It's totally inexpensive, and readily scavenges peroxynitrite. I'll leave the superoxide to my dismutase enzymes, which work best with lots of alphalipoic backing them up.
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> Think I might try inosine to see how it feels - my only concern was if it raises adenosine, could it affect the adenosine receptor? Also does xanthine oxidase have any negative effects.I'm far more interested in ensuring adequate peroxynitrite scavenging than I am about anything else that might occur. It may be that my inherent belief (formed over many years) that I require a high protein diet, is directly related to the high inosine production that it promotes.
I need to do a "clean" inosine trial, all by its lonesome, but my current intake of other stuff won't really allow it.
> >
> > > The balance of arginine/NOS/biopterin/methylation seems important. Low biopterin or low arginine can switch NOS to produce superoxide instead of nitric oxide. Arginine without methyl factors can increase homocysteine.http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=324552
If you look at figure 1 (the link is hard to find, but it's right after reference 8 in the text), you'll see that superoxide itself oxidizes biopterin, so the relationship is complex. You're quite right about arginine depletion.
> > how?
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> 'Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: implications for uncoupling endothelial nitric-oxide synthase.'
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> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12692136Reading this, I see the critical utility of ascorbate in restoring biopterin radical. What you have is a free radical chain of superoxide (+ NO) --> peroxynitrite --> BH3· --> ascorbate·
The latter is unreactive.Ascorbic acid also directly compete with NO for superoxide anion, so it has multiple quenching effects in this chain.
> "Recent evidence also indicates that iNOS-induced pathophysiological effects involve substrate deficiency. Thus, at low concentrations of L-arginine iNOS produces both NO and superoxide anions, which results in the increased synthesis of the highly reactive, detrimental oxidant peroxynitrite"
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> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12967769The apparent cause here is regulatory, in that arginase is increased, and uptake reduced. The cell is deprived of arginine, but it is not necessarily true that the organism is. Interesting though, as the obvious solution would seem to be more arginine.
> "Both endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) isoforms are expressed in the atherothrombotic vasculature and, owing to a loss of substrate or reducing cofactors required for NO synthesis, undergo enzymatic "uncoupling" leading to both a loss of NO production and an increase in superoxide anion generation."
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> "Owing to the sizeable methylation stress created by supplemental L-arginine in these animals (creatine synthesis accounts for 70% of the total utilization of labile methyl groups in mammals under normal circumstances16), the remethylation of homocysteine to methionine would be limited. Thus, transsulfuration, which is localized principally to the liver, is likely to have been the principal metabolic mechanism for eliminating the increase in homocysteine"
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> http://atvb.ahajournals.org/cgi/content/full/23/1/3Nice paper. I'm comforted by this quote:"Similarly, one might predict that dietary creatine supplementation would reduce de novo creatine synthesis by suppressing L-arginine:glycine amidinotransferase expression, thereby attenuating methylation stress and homocysteine production."
You helped me to grasp the significance of creatine vis a vis methylation stress. Hyperhomocysteinemia is a common finding in chronic depression, CFS, fibromyalgia, PTSD and related disorders. I've always advocated heavy supplementation of methyl donors, and this is another reason why.
> > MSM takes the load off of methionine for sulphation. How are you with methionine?
> >
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> I'm fine with methionine as long as I take methyl factors - otherwise, I'm awful! Do even better with it if I take a little lysine too - think carnitine is very important for me. Interesting that homocysteine is linked with apoptosis.Homocysteine is also a part of atherosclerosis, being one of the precipitating factors for inflammation in the first place.
> > Yes, me too. In then end, it's what makes you feel better, not whether you can explain why it does so.
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> Yes, I tend to try things first - if it feels good, I try to find out why - but frequently the first few attempts to understand can be misguided!
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> RayMore, anon.
Lar
poster:Larry Hoover
thread:404137
URL: http://www.dr-bob.org/babble/alter/20041123/msgs/427140.html