These are some articles [(http://scholar.google.com/scholar?q=hypoparathyroidism+mitochondrial&hl=en); Earle et al., 2004: (http://cat.inist.fr/?aModele=afficheN&cpsidt=15701034)] discussing the fact that mitochondrial disorders, caused by mitochondrial DNA deletions or other factors, can cause hypoparathyroidism and, as a consequence, hypocalcemia and can also coexist with proximal tubule dysfunction. The hypoparathyroidism in mitochondrial disorders results, most simply, from ATP depletion in the parathyroid glands, much as ATP depletion in beta cells impairs insulin secretion and can cause diabetes in people who have mitochondrial disorders (http://scholar.google.com/scholar?hl=en&q=mtDNA+insulin+beta+cells+ATP). The capacity of ATP depletion in the parathyroid glands to produce derangements in phosphate and calcium homeostasis has the potential to confound attempts at applying rigid diagnostic criteria to some of these abnormalities of phosphate homeostasis, even in a person who does not have any known mitochondrial disease, in my opinion. One reason for this is that phosphate depletion can cause ATP depletion and symptoms that are similar to those found in mitochondrial disorders (cardiomyopathy, skeletal muscle myopathy, liver dysfunction, encephalopathy, etc.). Magnesium deficiency can cause hypocalcemic hypoparathyroidism that's thought to result, in part, from a decrease in magnesium-dependent adenylate cyclase activity, resulting in cAMP depletion, in the parathyroid glands, although the cAMP depletion could also result from decreases in the activities of hexokinase and other glycolytic enzymes (leading to ATP depletion) whose activities are sensitive to magnesium availability. In the case of adenylate cyclase, however, magnesium serves a catalytic role (I think--it's very complex, and there's a lot of research on it) and allosteric regulatory roles.
I cited some research on the activation of adenylate cyclase by magnesium [(http://hardcorephysiologyfun.blogspot.com/2009/07/phosphate-diabetes-and-renal-threshold.html)], and the authors [Bush et al., 2001: (http://www.ncbi.nlm.nih.gov/pubmed/11767924)] discussed the fact that calcium ions inhibit adenylate cyclase activity and that there's this "feed-forward" inhibition that occurs, in magnesium deficiency, through the competitive and other inhibitory interactions, between magnesium and calcium, in the regulation of adenylate cyclase activity (in the parathyroid glands and in most other cells). MgATP2- also can produce allosteric activation of hexokinase [Bachelard, 1971: (http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1178047&blobtype=pdf)(http://www.ncbi.nlm.nih.gov/pubmed/5158910)], and the inhibitory effect of free ATP is not entirely due to competitive inhibition. It's thought to be partially due to negative allosteric cooperativity, etc. Bachelard (1971) also found that high Mg2+ concentrations can inhibit hexokinase (a glycolytic enzyme) activity, but an excess of intracellular magnesium is less likely, in my opinion, to be a problem for many people than magnesium depletion is. A lot of people still assume that all ATP is MgATP2-, but it's very much not the case. Magnesium depletion obviously does decrease the MgATP2-/ATP4- ratio, and that type of depletion is probably really complicated. Magnesium repletion is known to increase the activities of hexokinase and other glycolytic enzymes and to shift the Keq of creatine kinase, so as to increase the PCr/Cr ratio, in general [Garfinkel and Garfinkel, 1985: (http://www.ncbi.nlm.nih.gov/pubmed/2931560); (http://scholar.google.com/scholar?hl=en&q=magnesium+glycolytic)]. The effects of MgATP2- vs. ATP4- can be really complex and mind-bending, and not many people are even doing that kind of research anymore. Krebs et al. (2001) [Krebs et al., 2001: (http://jcem.endojournals.org/cgi/content/full/86/5/2153)(http://www.ncbi.nlm.nih.gov/pubmed/11344220?dopt=Abstract)] discussed the fact that inorganic phosphate (Pi) allosterically inhibits hexokinase and that elevations in unsaturated free fatty acids, especially, can inhibit phosphate transport, but I remember reading about the fact that there's some effect whereby the magnesium-induced activation of hexokinase activity (and the creatine kinase activity that's functionally coupled to hexokinase activity) can increase phosphate transport and simultaneously sequester phosphate in glucose-6-phosphate, a product of hexokinase activity. There's some interaction that can allow hexokinase activity to escape many of the normal, allosteric inhibitory mechanisms that would otherwise limit its activity, and that can disturb phosphate homeostasis in some way. I forget the details and will try to find the article(s) I'm thinking of, but supplementing with high doses of magnesium has the potential to disturb phosphate metabolism (and vice-versa).
But the point of my discussion of the hypoparathyroidism in mitochondrial disorders is that the short-term parathyroid hormone response to phosphate repletion, even through the diet, could be exaggerated or could be blunted. It could be extremely complicated in the context of intracellular phosphate depletion. That's one reason it's worthwhile to be extremely careful with phosphate supplementation. I did some calculations and have read through a lot of articles, and I don't think that the amount of phosphate in commonly-used dosages of ATPNa2 (even from the dosages of ATPNa2 that I'd consider to be on the "higher end" and that would provide an amount of adenosine equivalent to the "adenosine" that can be derived from 3,600 mg of SAM-e, for example) would be very likely to pose a danger, but it's something one would want to discuss with one's doctor, especially if one had kidney disease or is in some disease state. Even the amount of phosphate from that type of dosage would be only about 1600-1800 mg (600-700 mg, or something, of elemental phosphorus), and that's within the range of dietary variation in phosphate intake. The articles on phosphorus metabolism are very problematic, in many cases, and they're extremely sloppy with molar conversion factors. I'll try to put up some of the examples, but it's potentially a really serious issue to make a bad calculation. It's a very common problem in the phosphate articles.
But the point with the mitochondrial issue is that there could be just these kinds of chaotic issues with calcium and phosphate homeostasis in the context of longstanding hypophosphatemia/intracellular phosphate depletion. That's one reason that drawing facile conclusions about the dangers of phosphate, based on parathyroid hormone levels or markers of bone resorption that show up after one large, excessive dosage of sodium phosphate, aren't very useful. Why could that occur, supposing it does? I've read a few articles discussing the contributions of phosphate-induced changes in gluconeogenesis or glycolysis in osteoblasts or osteoclasts [not very good searches, but, nonetheless: (http://scholar.google.com/scholar?q=%22inorganic+phosphate%22+osteoblast+gluconeogenesis+OR+glycolysis&hl=en); (http://scholar.google.com/scholar?hl=en&q=hypophosphatemic+rickets+gluconeogenesis+OR+glycolysis)] can play in some of the bone-related abnormalities in people with genetic, hypophosphatemic rickets (or in animal models, etc.). That's the type of thing that could also derange calcium and phosphate metabolism in people who are phosphate depleted. Maybe the "excess" of phosphate is pro-apoptotic in osteoblasts because of some short-term derangement of glycolytic activity. Some of these conclusions about pathological effects of single dosages of phosphate might be based on hasty conclusions and flawed reasoning about causation and mechanisms, etc.
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