The most abundant intracellular anion is free phosphate (Pi). However, the majority of the body's phosphorus, around 85%, exists as inorganic hydroxylapatite. The remaining phosphorus is found in organic compounds within cells, such as phospholipids, nucleic acids, ATP, and creatine phosphate. ATP provides phosphate for kinases, while Pi is used by phosphorylases, including glycogen phosphorylase. Phosphorus is widely present in food, with milk being a good source. Dietary deficiency of phosphorus is rare, but hypophosphatemia can occur due to various factors such as refeeding carbohydrates to malnourished patients, overuse of aluminum-containing antacids, and increased urinary loss in response to elevated production of PTH. Muscle weakness is a common symptom of hypophosphatemia. Hyperphosphatemia, on the other hand, is primarily caused by decreased PTH levels. Excess phosphate can combine with calcium ions and form crystals that deposit in soft tissues, leading to metastatic calcification. Hormonal regulation plays a crucial role in controlling serum levels of calcium and phosphate. Calcitriol and PTH respond to low serum calcium by increasing bone resorption, intestinal absorption, and renal reabsorption of calcium and phosphate. Calcitriol is produced by the kidneys, while PTH is secreted by the parathyroid glands. Unlike calcitriol, PTH decreases phosphate reabsorption in the kidneys, resulting in lower serum phosphate levels. High serum phosphate levels, in turn, increase PTH and decrease calcitriol production. Calcitonin, released by the C cells of the thyroid gland, acts in response to elevated serum calcium levels by promoting bone mineralization and increasing renal excretion of calcium and phosphate. Moving on to magnesium, approximately 60% of the body's magnesium is stored in bones, accounting for only 1% of the bone mass. Magnesium is essential for numerous enzymatic reactions, including phosphorylation by kinases and phosphodiester bond formation by DNA and RNA polymerases. While magnesium is found in a wide variety of foods, the average intake in the United States is below the recommended level. Hypomagnesemia can occur due to decreased absorption or increased excretion of magnesium. Symptoms of hypomagnesemia include hyperexcitability of skeletal muscles and nerves, as well as cardiac arrhythmias. On the other hand, hypermagnesemia can lead to hypotension. Sodium, chloride, and potassium are also important electrolytes.
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