The authors of this article [Giovannini et al., 2002: (http://www.shockjournal.org/pt/re/shock/fulltext.00024382-200208000-00003.htm)(http://www.ncbi.nlm.nih.gov/pubmed/12166771)] found that a low serum phosphate level was associated with a four-fold increase in the incidence of complications in people who had had hepatectomies. In the people who started to deteriorate after the surgeries, the authors found that the deterioration essentially "progressed" from hypophosphatemia to hypocholesterolemia and then death. So one interpretation is that the low phosphate availability led to the extremely low serum cholesterol level and that the low phosphate availability seemed to be associated with a deterioration of liver function. I've seen other articles in which the implication has been that the liver disease interfered with the maintenance of the serum and extrahepatic, intracellular phosphate availability, perhaps by multiple mechanisms. Malabsorption, such as can result from steatorrhea, is common in liver disease and is known to have the potential to reduce phosphate absorption, and that's probably one mechanism. But, in a number of the articles I've cited in past postings, the implication (or direct statement) has been that the phosphate depletion caused the liver disease. There could be a feed-forward deterioration in the capacity to maintain serum and intracellular phosphate levels. Giovannini et al. (2002) gave either sodium phosphate or fructose 1,6-diphosphate to some patients.
One interpretation is that decreases in intracellular phosphate levels impair cholesterol biosynthesis, and Jankowski et al. (2009) [Jankowski et al., 2009: (http://www3.interscience.wiley.com/journal/122467220/abstract)], as discussed in a past posting (http://hardcorephysiologyfun.blogspot.com/2009/06/endogenous-formation-of-dinucleotide.html), were basically saying that cholesterol biosynthesis consumes a lot of ATP and sequesters a lot of phosphate in intermediates, such as farnesyl pyrophosphate, etc. Phosphate depletion is known to decrease ATP formation, as discussed by Giovannini et al. (2002), and could conceivably limit the rate of cholesterol biosynthesis. When one considers the increased demand for cholesterol formation that would occur after a surgery, it's not surprising that there would be a higher demand for phosphate.
That type of research could be relevant to an understanding of the association of low serum cholesterol levels with increases in the risk of suicide. There tends to be an extreme and unrelenting activation of the noradrenergic stress response pathways in the brain in people who are severely depressed, and that can lead to a state of glucocorticoid resistance that has traditionally been compared to the hypermetabolic state that occurs in people after a burn injury (that's the type of postsurgical or post-injury state that's characterized by glutamine depletion and, not infrequently, hypophosphatemia) [(http://scholar.google.com/scholar?hl=en&q=burn+glucocorticoid+psychiatry); (http://scholar.google.com/scholar?hl=en&q=burn+glucocorticoid+glutamine); (http://scholar.google.com/scholar?hl=en&q=glucocorticoid+hypophosphatemia)]. When an article says that glucocorticoids can cause hyperphosphatemia, that's likely to be a short-term effect. Fructose, for example, can elevate serum phosphate by causing hepatic ATP depletion, but the phosphate is then excreted, to a large extent. The longer-term effect of chronic fructose "ingestion" is more likely to be phosphate depletion, both intracellularly and extracellularly. But glucocorticoids often cause effects in the short term that are the opposite of their effects in the short term, and I'm referring to effects on phosphate homeostasis and countless other processes. But the point is that the activation of the noradrenergic stress response pathways can become counterproductive in severe depression and could produce phosphate depletion over time, and that could impair ATP-dependent cholesterol formation in the brain and simultaneously lead to an upregulation of the enzyme protein concentrations and activities of the cholesterol biosynthetic enzymes in the brain. That could further sequester phosphate in mevalonate pathway intermediates and sequester phosphate, leading to ATP depletion in neurons and astrocytes. Given all the research associating ATP depletion and impairments in energy metabolism with depression (and the research associating phosphate depletion with neurological problems and malaise or pain states or fatigue, etc.), it's conceivable that phosphate depletion could contribute to low serum or brain cholesterol levels in some people who die by violent suicide (http://scholar.google.com/scholar?hl=en&q=violent+cholesterol+suicide+OR+death).
I know that's a disturbing topic, but I just put these suggestions up on the blog and try to think about the mechanisms. The mechanisms are really complicated, but I think the association has something to do with impairments in energy metabolism in severe forms of depression. It's interesting that hypocholesterolemia (low serum cholesterol) shows up in animals that display diminishments in adrenal function (http://scholar.google.com/scholar?hl=en&q=hypocholesterolemia+glucocorticoid) and also shows up in people who have a variety of different mitochondrial disorders (http://scholar.google.com/scholar?hl=en&q=hypocholesterolemia+mitochondrial+OR+mitochondria+OR+mtDNA) (mtDNA mutations, mainly, although one would expect an acquired form of mitochondrial dysfunction to have the potential to produce the same impairments in cholesterol biosynthesis in the liver, etc.). Hypocholesterolemia is also common in inflammatory disease states (http://scholar.google.com/scholar?hl=en&q=hypocholesterolemia), and pro-inflammatory cytokines are known to impair mitochondrial function, in the short term and long term, by increasing nitric oxide formation and by the more direct activation of various mitogen-activated protein kinase cascades, etc. (http://scholar.google.com/scholar?hl=en&q=mitochondrial+cytokine+energy+%22pro-inflammatory%22+OR+proinflammatory).
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