Calcium metabolism

Calcium metabolism refers to the movements and regulation of calcium ions (Ca2+) in and out of various body compartments, such as the gastrointestinal tract, the blood plasma, the extracellular and intracellular fluids, and bone tissue. An important aspect of calcium metabolism is plasma calcium homeostasis, the regulation of calcium ions in the blood plasma within narrow limits. In this process, bone tissue acts as a calcium storage center for deposits and withdrawals as needed by the blood, via continual bone remodeling.:276–277 Derangement of this mechanism leads to hypercalcemia or hypocalcemia, both of which can have consequences for health. The level of the calcium in humans' plasma is regulated by calcitonin and parathyroid hormone (PTH); calcitonin is released by the thyroid gland when its plasma level is above its set normal point (in order to lower calcium level); PTH is released by the parathyroid glands when calcium level falls below set point (in order to raise it).Cholesterol ultraviolet→ Previtamin D3 isomerization→ Vitamin D3 Liver→ Calcifediol PTH + Kidneys→ Calcitriol Calcium metabolism refers to the movements and regulation of calcium ions (Ca2+) in and out of various body compartments, such as the gastrointestinal tract, the blood plasma, the extracellular and intracellular fluids, and bone tissue. An important aspect of calcium metabolism is plasma calcium homeostasis, the regulation of calcium ions in the blood plasma within narrow limits. In this process, bone tissue acts as a calcium storage center for deposits and withdrawals as needed by the blood, via continual bone remodeling.:276–277 Derangement of this mechanism leads to hypercalcemia or hypocalcemia, both of which can have consequences for health. The level of the calcium in humans' plasma is regulated by calcitonin and parathyroid hormone (PTH); calcitonin is released by the thyroid gland when its plasma level is above its set normal point (in order to lower calcium level); PTH is released by the parathyroid glands when calcium level falls below set point (in order to raise it). Calcium is the most abundant mineral in the human body. The average adult body contains in total approximately 1 kg, 99% in the skeleton in the form of calcium phosphate salts. The extracellular fluid (ECF) contains approximately 22 mmol, of which about 9 mmol is in the plasma. Approximately 10 mmol of calcium is exchanged between bone and the ECF over a period of twenty-four hours. The concentration of calcium ions inside the cells (in the intracellular fluid) is more than 7,000 times lower than in the blood plasma (i.e. at <0.0002 mmol/L, compared with 1.4 mmol/L in the plasma) Calcium has several main functions in the body. It readily binds to proteins, particularly those with amino acids whose side chains terminate in carboxyl (-COOH) groups (e.g. glutamate residues). When such binding occurs the electrical charges on the protein chain change, causing the protein's tertiary structure (i.e. 3-dimensional form) to change. Good examples of this are several of the clotting factors in the blood plasma, which are functionless in the absence of calcium ions, but become fully functional on the addition of the correct concentration of calcium salts. The voltage gated sodium ion channels in the cell membranes of nerves and muscle are particularly sensitive to the calcium ion concentration in the plasma. Relatively small decreases in the plasma ionized calcium levels (hypocalcemia) cause these channels to leak sodium into the nerve cells or axons, making them hyper-excitable (positive bathmotropic effect), thus causing spontaneous muscle spasms (tetany) and paraesthesia (the sensation of 'pins and needles') of the extremities and round the mouth. When the plasma ionized calcium rises above normal (hypercalcemia) more calcium is bound to these sodium channels having a negative bathmotropic effect on them, causing lethargy, muscle weakness, anorexia, constipation and labile emotions. Because the intracellular calcium ion concentration is extremely low (see above) the entry of minute quantities of calcium ions from the endoplasmic reticulum or from the extracellular fluids, cause rapid, very marked, and readily reversible changes in the relative concentration of these ions in the cytosol. This can therefore serve as a very effective intracellular signal (or 'second messenger') in a variety of circumstances, including muscle contraction, the release of hormones (e.g. insulin from the beta cells in the pancreatic islets) or neurotransmitters (e.g. acetylcholine from pre-synaptic terminals of nerves) and other functions. Calcium acts structurally as supporting material in bones as calcium hydroxyapatite (Ca10(PO4)6(OH)2). In skeletal and heart muscle calcium ions, released from the sarcoplasmic reticulum (the endoplasmic reticulum of striated muscles) binds to the troponin C protein present on the actin-containing thin filaments of the myofibrils. The troponin's 3D structure changes as a result, causing the tropomyosin to which it is attached to be rolled away from the myosin-binding sites on the actin molecules that form the back-bone of the thin filaments. Myosin can then bind to the exposed myosin-binding sites on the thin filament, to undergo a repeating series of conformational changes called the cross-bridge cycle, for which ATP provides the energy. During the cycle, each myosin protein ‘paddles’ along the thin actin filament, repeatedly binding to myosin-binding sites along the actin filament, ratcheting and letting go. In effect, the thick filament moves or slides along the thin filament, resulting in muscle contraction. This process is known as the sliding filament model of muscle contraction. The plasma total calcium concentration is in the range of 2.2-2.6 mmol/L (9-10.5 mg/dL), and the normal ionized calcium is 1.3-1.5 mmol/L (4.5-5.6 mg/dL). The amount of total calcium in the blood varies with the level of plasma albumin, the most abundant protein in plasma, and therefore the main carrier of protein-bound calcium in the blood. The biologic effect of calcium is, however, determined by the amount of ionized calcium, rather than the total calcium. It is therefore the plasma ionized calcium level which is tightly regulated to remain within very narrow limits by homeostatic negative feedback systems. Between 35-50% of the calcium in plasma is protein-bound, and 5-10% is in the form of complexes with organic acids and phosphates. The remainder (50-60%) is ionized. The ionized calcium can be determined directly by colorimetry, or it can be read off from nomograms, though the usefulness of the latter is limited when the pH and protein content of the plasma deviate widely from the normal.