2. Phosphorus: Free phosphate (Pi) is the most abundant intracellular anion. However, 85% of the body’s phosphorus is in the form of inorganic hydroxylapatite, with most of the remainder in intracellular organic compounds such as phospholipids, nucleic acids, ATP, and creatine phosphate. Phosphate is supplied as ATP for kinases and as Pi for phosphorylases (for example, glycogen phosphorylase, see p. 128). [Note: Its addition (by kinases) or removal (by phosphatases) is an important means of covalent regulation of enzymes (see Chapter 24).] Phosphorus is widely distributed in food (milk is a good source), and dietary deficiency is rare. Hypophosphatemia can be caused by refeeding carbohydrates to malnourished patients (refeeding syndrome, see p. 369), overuse of aluminum-containing antacids (aluminum chelates Pi), and increased urinary loss in response to increased production of PTH (see below). Muscle weakness is a common symptom. Hyperphosphatemia is caused primarily by decreased PTH levels. The excess Pi can combine with Ca2+ and form crystals that deposit in soft tissue (metastatic calcification). [Note: The Ca2+/Pi ratio is important for bone formation (the ratio is ~2/1 in bone), and some experts are concerned that replacement of Ca2+-rich milk by Ca2+-poor, Pi-rich soft drinks can affect bone health.] 3. Hormonal regulation: Serum levels of Ca2+ and Pi are primarily controlled by calcitriol (1,25-dihydroxycholecalciferol, the active form of vitamin D) and PTH, both of which respond to a decrease in serum Ca2+ . Calcitriol, produced by the kidneys, increases serum Ca2+ and Pi by increasing bone resorption and intestinal absorption and renal reabsorption of Ca2+ and Pi (Fig. 29.2). PTH (from the parathyroid glands) increases serum Ca2+ by increasing bone resorption, increasing renal reabsorption of Ca2+ , and activating the renal 1-hydroxylase that produces calcitriol from calcidiol (see p. 390) (Fig. 29.3). In contrast to calcitriol, PTH decreases Pi reabsorption in the kidneys, lowering serum Pi. [Note: High serum Pi increases PTH and decreases calcitriol.] A third hormone, calcitonin (from the C cells of the thyroid gland), responds to elevated serum Ca2+ levels by promoting bone mineralization and increasing renal excretion of Ca2+ (and Pi).
B. Magnesium
About 60% of the body’s Mg2+ is in bone, but it accounts for just 1% of the bone mass. The mineral is required by a variety of enzymatic reactions, including phosphorylation by kinases (Mg2+ binds the ATP cosubstrate) and phosphodiester bond formation by DNA and RNA polymerases. Mg2+ is widely distributed in foods, but the average intake in the United States is below the recommended level. Hypomagnesemia can result from decreased absorption or increased excretion of Mg2+ . Symptoms include hyperexcitability of skeletal muscles and nerves and cardiac arrhythmias. With hypermagnesemia, hypotension is seen. [Note: Magnesium sulfate is used in the treatment of preeclampsia, a hypertensive disorder of pregnancy.]
C. Sodium, chloride, and potassium