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Old 12-25-2012
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Question Hyperphosphatemia and one alpha Hydroxylase!

Can Any1 Explain the effect of Hyperphosphatemia on 1 alpha hydroxylase?
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Old 12-25-2012
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Ca2+ * PO-4 > solubility product = Bone deposition
this mean increase in phosphate cause deposition of calcium so dec calcium plasma level so cause increase in PTH level which lead to inc in alpha 1 hydroxylase level in proximal tubules cells.
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Old 12-25-2012
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Hyperphosphatemia inhibits 1 alpha hydroxylase in the proximal tubule, which further inhibits the conversion of 25-hydroxy-vitamin D3 into its active metabolite 1,25 dihydroxy-vitamin D3. We need the 1 alpha hydroxylase to convert calcium into its active state. 1 alpha hydroxylase results in vitamin D deficiency which will result in hypocalcemia, leading to a defective gastrointestinal calcium absorption. The decrease in the active vitamin D production is somewhat offset b/e the hyperphosphatemia will stimulate secretion of PTH which will increase activity of 1 alpha hydroxylase resulting in a neutral effect. Increase in PTH and decrease in vitamin D will inhibit renal and intestinal absorption of phosphate. *just a note: hyperphosphatemia stimulated PTH secretion pathway is not yet known.
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Default PTH/ Vit D/ Ca++ homeostasis

High PO4 --> Inhibition of PTH via feedback inhibition --> decreases 1 alpha hydroxylase activity

Because PTH normally has 4 effects
1) Activating 1 alpha hydroxylase
2) Increasing PO4 excretion by the kidneys
3) Enhances the release of Ca++ from bones (by activating osteoblasts to activate osteoclasts)

and 1 alpha hydroxylase has the following effect
25 OH Vit D--> 1,25 (OH)2 Vit D (which is the active form)

and 1,25 (OH)2 Vit D has the following effect:
1) Increasing the reabsorption of Ca++ in the kidney
2) Increasing the absorption of Ca++ from food in the gut
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Biochemistry-, Electrolytes-, Physiology-

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