Human Biochemistry, Volume 2 - Murray R. 1993

Biochemistry of Intracellular and Intercellular Communications
Hormones Regulating Calcium Metabolism
Calcium Homeostasis

The primordial ocean was rich in K⁺ and Mg²⁺, which is why Proteins that emerged during evolution function most effectively in precisely this environment. Over time, the composition of seawater changed, making Na⁺ and Ca²⁺ the predominant ions. Consequently, to ensure optimal conditions for intracellular protein function, a mechanism evolved to restrict the concentration of Na⁺ and Ca²⁺ inside Cells while maintaining high levels of K⁺ and Mg²⁺. Membrane-bound sodium and calcium pumps served as this mechanism, capable of maintaining a steep ion concentration gradient (up to 1000-fold in the case of Ca²⁺) between the Cytosol and the extracellular fluid. In modern Multicellular Organisms, Na⁺ and Ca²⁺ are the primary ions of the extracellular environment. Hormones and other BIOLOGICALLY ACTIVE SUBSTANCES induce rapid, transient changes in calcium ion fluxes across Cell/30.html">The Plasma Membrane and between intracellular compartments. As a result, Calcium Ions act as intracellular messengers that regulate A wide variety of metabolic processes (see Chapter 44).

The transition from an aquatic environment rich in Ca²⁺ to a terrestrial habitat where this element is relatively scarce required The Development of a sophisticated calcium Homeostasis mechanism. This system ensures the extraction of Ca²⁺ from dietary sources and prevents sharp fluctuations of Ca²⁺ concentration in the extracellular fluid (ECF). This mechanism involves three hormones—parathyroid hormone (PTH), calcitriol [1,25(OH)₂-D₃], and Calcitonin (CT)—acting upon three target Organs: bones, Kidneys, and intestines. When the plasma ionized calcium level falls below the critical threshold (<1.1 mmol/L), the Parathyroid glands increase PTH secretion. PTH stimulates the release of calcium and phosphate from bone into the bloodstream, as well as enhancing renal calcium reabsorption and phosphate excretion.

The second crucial aspect of PTH action on the kidneys is The stimulation of 1,25(OH)₂-D₃ synthesis. Now known as calcitriol, this compound is the active form of what was formerly called vitamin D. Calcitriol acts on the intestines to enhance calcium absorption and appears to play a permissive role in the effects of PTH on bone and kidneys. The coordinated actions of these agents are aimed at increasing extracellular Ca²⁺ levels while keeping phosphate levels constant or reduced. Once extracellular Ca²⁺ concentration returns to normal, PTH secretion is suppressed via a negative feedback loop. Elevated Ca²⁺ levels also inhibit calcitriol synthesis (partially by reducing PTH), while simultaneously increasing The production of inactive metabolites of this compound. All of these factors lead to a decrease in intestinal calcium absorption and diminished effects of PTH on the kidneys and Skeleton. In some animals, an increase in extracellular Ca²⁺ levels triggers calcitonin (CT) secretion by C-cells of The Thyroid Gland or ultimobranchial bodies. In humans, The Physiological Role of CT in calcium homeostasis remains unclear; however, some in vitro data suggest that CT can inhibit bone resorption.