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Re: dopamine oxidation .... to Ray...and » tealady

Posted by Larry Hoover on November 25, 2004, at 5:41:10

In reply to Re: dopamine oxidation .... to Ray...and » Larry Hoover, posted by tealady on November 14, 2004, at 4:04:46

> > I looked at the toxicity of vitamin C, and two possible mechanisms come to mind. One involves iron toxicity, exacerbated by the activation by ascorbate. Those with hemochromatosis are particularly vulnerable to this effect. The other mechanism involves enhanced excretion of uric acid. That might leave one vulnerable to peroxynitrite, as uric acid is an excellent peroxynitrite scavenger.
> >
> I think I have a problem with peroxynitrate (amongst other things).
> Lar,
> In your opinion if one produce a lot of urine(say 6L a day) and it seemed to be produced faster than would be expected (I guess this happens as I always have problems with ultrasounds:) is that what you mean by enhanced excretion of uric acid??

High urine output is polyuria, which is usually associated with dilute urine. Ascorbate increases the rate of uric acid clearance, which would mean lower blood concentrations.

> > > So ascorbate could produce more ascorbyl radicals than glutathione could mop up before I started running low on NADPH.
>
>
> Maybe that is what happens to me as well
>
> >With NADPH running low, hydrogen ions build up in the cell, the pH drops, all enzymes fail, and I end up with millions more free radicals that I started with!
>
> Hmm I don't think it works like that, hydrogen ions are after NADH is made..in the chemiosmosis the next stage..and the NADH has its electrons passed along the mitochondrial membrane and H+ ions get pumped into the intermembrane space thru the proton pumps (NADH-ubiquinone oxidoreductase, then ubiquinone-cytochrome c oxidoreductase, then cytochrome c oxidase) .. and in the last one Oxygen is consumed and water formed...or something like that

The acidotic response is also mediated by bicarbonate pumps, as there is always a ready supply of bicarbonate in the blood. Acid stress in a cell is almost a theoretical entity, in the sense that it never really gets very far. If it did, you'd be at the hospital right quickly.

> > I really doubt there's a pH mechanism at play. There are many many ways for cells to adjust pH. There are substantial buffer systems in place, just for that purpose. Do you understand the chemistry of buffer systems?
> >
>
> Umm Lar I have high Cl-(topmof range) and low bicarbonate ions(bottom of range)...so that would indicate what?? pH related??

It would indicate that you might be in the initial stages of metabolic acidosis. What is your anion gap? Is creatine clearance normal? I'm thinking your kidneys might not be up to snuff.

> Remember I once said I didn't get all this acid/base stuff..well I still don't really get it..the buffer sytems..but I'm beginning to grasp a little.

With a low bicarbonate, your buffer system is weaker than it ought to be. The bicarbonate ion serves as a "sponge", to decrease the pH change that comes from normal changes in metabolic rate. You're more likely to suffer from exercise exhaustion, for example. Your body tends towards being acid, with low bicarbonate.

Lar

 

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