Posted by tealady on December 10, 2004, at 15:47:54
In reply to Re: dopamine oxidation » raybakes, posted by Larry Hoover on December 10, 2004, at 8:39:40
> > 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....
>I'm confused too...but that's pretty much the norm:-) Some of these are good as well as perhpas bad ..like oxygen is like good,and peroxides as well I guess...
and I think peroxynitrite is always bad?
well you can see the confusion
> 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.
> >
> > 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.
>How about trying to stop the peroxidase from occuring in the first place? Is this a possibility?
Here's a bit of background
I've usually got lowish ferritin. I'd like it to be over 50. To low ferritin levels makes it difficult to tolerate adequte thyroid hormones, leading to anxiety and other symptoms, result is a lower BMR than is probably desirable...and lowish iron/ferritin causes depression in me too.
Before supplementation with iron ferritin was 15 , three years ago.
With a series of 3 injections I got it up to 55(after first injection I felt happier than believable..singing on train even!..and sno situation change at all), but it soon fell down to 20's (I think). With iron supps over many months I got it up to 37 in 2002.
I took iron supps, liquid and tablet on and off...more on than off!
I was feeling depressed after an endo visit (6th October) and got the chemist to make me up some strong ferrous gluconate (500mg/5ml), which worked in getting me out of depression. Started 6th October.
But after a few weeks I felt like I want to lash out but I was not sure at what or why.
(is this a high iron, choline/acetylcholine thing?..can't find anything on, but that's another topic).That was on the 6th Nov,04. (so about a month on high liquid iron)..always taken with a meat meal, like steak and usually with a bit of VitC too...and usually with then the fish oil, VitE , CoQ10 etc.
I stopped the selenium ,iron, lecithin I was taking(and the fish oil, CoQ10, VitE as well) and had my iron tested on 24th Nov...so that's 18 days later
results were (after being off iron supps for 18 days)
Serun Iron 38 umol/L (10-30) ****HIGH*** 212.3 mcg/dL (US units)
Transferrin 42 umol/L (27-53) can't find a unit conversion to US
Transferrin Saturation 46% (12-45) **HIGH**Serum Ferritin 37 ug/L
So the ferritin hadn't gone up (OK , it may have dropped and then rose again)
I seem to be able to absorb iron into my bloodstream just fine....but for some reason I don't get that iron easily into ferritin..
I put this on the thyroid forumas there are a few there who have difficulty getting feritin up too..
Got a lot of help and it looks like its NO to blame again with me..which fits as my skin goes like supersensitive sometimes, and I get inflammation too.think I get hypoxia too, which is why long doses of Coq10 backfire with me..something to do with all this oxidisation...
Now I'm also wondering if serum ferritin measures the cytolsolic ferritin, all ferritin or just extracellular if that exists!..any idea?
Oh yes, one more that ties in that glutiathione I was craving for a while (over that intense craving as of this week)
http://www.ccia.org.au/page.php?id=102
It's just that all of this ties in with what is being discussed on here by Ray as well.One day I'll get back to replying Lar on the ADH, osmosis stuff...been occupied by this lately and still awaiting reults of 2nd ADH (arginine vasopressin) test done under water restriction and fasting etc conditions.( First test showed undetectable ADH.) One thing though with water restriction all my electroyltes and even albumin(back right mid normal was lowish) look great!..so that's been my problem there
Jan
> 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?
> >
> > 'Interactions of peroxynitrite, tetrahydrobiopterin, ascorbic acid, and thiols: implications for uncoupling endothelial nitric-oxide synthase.'
> >
> >
> > http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12692136
>
> Reading 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"
> >
> > http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12967769
>
> The 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."
> >
> > "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"
> >
> > http://atvb.ahajournals.org/cgi/content/full/23/1/3
>
> Nice 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?
> > >
> >
> > 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.
> >
> >
> > 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!
> >
> > Ray
>
> More, anon.
>
> Lar
poster:tealady
thread:404137
URL: http://www.dr-bob.org/babble/alter/20041123/msgs/427343.html