Metabolism, Parathyroid Hormone, and Calcitriol

Calcium is the most abundant mineral in the human body. About 99% is in the bones and teeth where it plays a structural role and the remaining 1% is in the body tissues and fluids where it is essential for muscle contraction, nerve impulse transmission, and cell metabolism. 

Extracellularly, calcium ions circulate in the blood plasma and interstitial fluid (Sect. 3.3.1). In blood plasma, calcium ions are chelated to albumin and citrate. Albumin (mol. wt. 66,700 kDa) is present at 50-60 mg/mL in plasma, corresponding to 0.9 m mol/L. Although plasma albumin has many different sites that can chelate calcium ions in vitro, only one site binds to calcium ions at physiological albumin concentrations and pH. Thus, albumin binds 0.9 mmol/L of free plasma Ca2+. In addition, citrate (Fig. 10.7), a tricarboxylic acid that the liver secretes into plasma, chelates a free calcium ion to two of its three carboxyl groups, replacing two Na+ ions. Citrate has a molar concentration of 0.08 mM in venous blood and therefore binds to an equivalent concentration of free calcium. Because the total calcium ion concentration of venous blood is 1.14 mmol/L (range 0.2), and the free calcium ion concentration is 0.1 mM, it appears that 0.15 mM of the plasma calcium ion concentration is bound to other plasma components. 

The free calcium ions in blood and extracellular fluid are critical for building and maintaining an adequate bone mass, and also for preventing excessive calcification. The sensor that regulates the free calcium ion concentration of plasma is within the parathyroid glands, where it controls the secretion of parathormone (PTH). This 84 amino acid peptide is split from a large, precursor protein and retained in secretory vesicles. If the concentration of free calcium ions drops below a critical level in blood plasma, the gland is activated to secrete PTH into the bloodstream. 

Osteoblasts and kidney cells respond to PTH by possessing a single receptor known as the Parathyroid hormone/Parathyroid hormone-Related protein receptor (PPR). The PTH-mediated activation of the osteoblast PPR receptor reduces OCIF (osteoprotegerin) 

Calcium ions are mostly present in bones or chelated to biological molecules. In blood plasma, only 1% of the calcium ions present are unbound 78% is bound to albumin, 8% to citrate, and 13% to other plasma proteins. The free calcium ions are prevented from precipitating by plasma pyrophosphate. Calcium ions are also stored in the endoplasmic reticulum (ER), mostly chelated to ER-resident proteins and phosphatidylser-ine. Free calcium ions may be released through transient receptor potential channels to the cytosol where it activates numerous physiological processes. If the free calcium ion concentration of blood plasma falls, parathyroid hormone (PTH) is secreted by the parathyroid gland cells. PTH speeds up the transport of demineralized bone products by osteoclasts. In the kidney, it increases the excretion of phosphate and decreases the excretion of calcium. PTH also acts on kidney cells to make calcitriol from vitamin D, which induces calcium transporters in the intestine and osteoclasts. PTH mediates these effects by activating G-protein-coupled receptors in the kidney and osteoclasts. 

---