Posted by Larry Hoover on November 11, 2004, at 10:56:35
In reply to Re: dopamine oxidation » Larry Hoover, posted by raybakes on November 11, 2004, at 5:06:01
> Hi Larry,
OK, you bum, you made me get out my textbooks.
> I've been reading abstracts like this one recently, and maybe it's explains why we don't see things in a similar way? The article you attached, talks of the accumulation of lactic acid causing fatigue in a cell,
Right. Lactic acid causes muscle cells to register what we know as fatigue, by some unknown signalling method. Lactic acid accumulates to keep pyruvate from increasing to toxic levels from glycolysis. Glycolysis is anaerobic (doesn't require oxygen), consumes 2 ATP, produces 4 ATP, converts 2 NAD+ to NADH, releasing 2 protons, and 2 pyruvate. That is the source of the acid stress. 2 pyruvate can produce 2 lactate, but in the process, 2 NADH are changed back to NAD+, consuming 2 protons. Lactic acid accumulation is a measure of compensatory response to excess formation of pyruvate. Only if pyruvate is in excess is lactate produced. There is no net release of protons from lactate production. You end up with 2 ATP from each glucose molecule, but respiration dead ends at lactate. Lactate is readily exported from the cell, but it is really a marker for excess pyruvate. Circulating lactate is at least partially reconverted to glucose in the liver (at the expense of ATP, of course). Proton stress is proportional to pyruvate production via glycolysis.
> whereas the articles I've been reading talk of lactic acid being produced to reduce cellular acidosis.
>
> Biochemistry of exercise-induced metabolic acidosis.
>
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15308499
>
> 'When the ATP demand of muscle contraction is met by mitochondrial respiration, there is no proton accumulation in the cell, as protons are used by the mitochondria for oxidative phosphorylation and to maintain the proton gradient in the intermembranous space'It would also be just as true to say that there is also no pyruvate accumulation in the cell, under normal respiratory conditions. Under excess anaerobic ATP production via glycolysis, the net accumulation in the cytosol from one glucose is 2 pyruvate, 2 protons (H+), and 2NADH. Pyruvate is taken into the mitochondrion as the base substrate for oxidative formation of ATP. Cytosolic NADH reacts with mitochondrial NAD+ (in essence, they switch places), with the net effect of pumping protons *out* of the mitochondrion. That is really the source of the cytosolic proton excess....mitochondrial respiration. In the mitochondria, 2 NADH + 2 H+ + O2 --> 2 NAD+ + 2 H2O. The cytosolic proton excess, however, comes at the expense of cytosolic NAD+, so acidosis may be a sign of NAD+ deficiency. There are many ways of looking at the same animal.
To summarize, there is always an ongoing balancing act between glycolysis (cytosolic) and oxidative respiration (mitochondrial). Whenever the mitochondria fall behind demand for ATP, the pyruvate production is imbalanced, and compensatory lactate is formed. However, lactate formation regenerates NAD+, and mops up protons, at the expense of energy efficiency.
Now, where we seem to part ways is on what comes first. Mitochondrial dysfunction is a very real entity, and I'm sure that it applies to my poor body. The root of mitochondrial dysfunction/low functioning is oxidative destruction of the two-layer mitochondrial membrane that is responsible for maintaining the proton/NAD shuttle. I see the oxidative stress as the root, and acidosis as the outcome.
> My interest is regarding my own brain fog, because if I improve buffering and support my mitochondria, my symtoms dramatically improve.
What is it, explicitly, that you do to improve buffering capacity? And separately, what do you do to support your mitochondria?
> Found this abstract on creatine as well..
>One thing at a time, Ray. I must pace myself.
Lar
poster:Larry Hoover
thread:404137
URL: http://www.dr-bob.org/babble/alter/20041108/msgs/414548.html