Calcium in biology

Calcium (Ca²⁺) plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization. Many enzymes require calcium ions as a cofactor; those of the blood-clotting cascade being notable examples. Extracellular calcium is also important for maintaining the potential difference across excitable cell membranes, as well as proper bone formation.

Calcium levels in mammals are tightly regulated with bone acting as the major mineral storage site. Calcium ions, Ca²⁺, are released from bone into the bloodstream under controlled conditions. Calcium is transported through the bloodstream as dissolved ions or bound to proteins such as serum albumin. Parathyroid hormone secreted by the parathyroid gland regulates the resorption of Ca²⁺ from bone, reabsorption in the kidney back into circulation, and increases the activation of vitamin D3 to Calcitriol. Calcitriol, the active form of vitamin D3, promotes absorption of calcium from the intestines and the mobilization of calcium ions from bone matrix. Calcitonin secreted from the parafollicular cells of the thyroid gland also affects calcium levels by opposing parathyroid hormone, however, its physiological significance in humans is dubious.

Animals

Vertebrates

Main article: Calcium metabolism

In vertebrates, calcium ions are of such vital importance to many physiological processes that its concentration is maintained within specific limits to ensure adequate homeostasis. This is evidenced by human plasma calcium, which is one of the most closely regulated physiological variables in the human body. Normal plasma levels vary between 1-2% over any given time. Approximately half of all ionized calcium circulates in its unbound form with the other half being complexed with plasma proteins such as albumin, as well as anions including bicarbonate, citrate, phosphate and sulfate.

Different tissues contain calcium in different concentrations. For instance, Ca²⁺ (mostly calcium phosphate and some calcium sulfate) is the most important (and specific) element of bone and calcified cartilage. In humans, the total body content of calcium is mostly present in the form of bone mineral (roughly 99%). In this state, it is largely unavailable for exchange/bioavailablity. The way to over come this is through the process of bone resorption, in which calcium is liberated into the bloodstream through the action of bone osteoclasts. The remainder of calcium is present within the extracellular and intracellular fluids.

Within a typical cell, the intracelluar concentration of ionized calcium is roughly 100nM, but is subject to increases of 10-100 fold during various cellular functions. The intracellular calcium level is kept relatively low with respect to the extracellular fluid, by an approximate magnitude of 12,000-fold. This gradient is maintained through various plasma membrane calcium pumps that utilize ATP for energy, as well as a sizable storage within intracellular compartments.

Effects

The effects of calcium on human cells are specific, meaning different types of cells respond in different ways. However, in certain circumstances its action may be more general. Ca²⁺ ions are one of the most widespread second messengers used in signal transduction. They make their entrance into the cytoplasm either from outside the cell through the cell membrane via calcium channels (such as Calcium-binding proteins or voltage-gated calcium channels), or from some internal calcium storages such as the endoplasmic reticulum and mitochondria. Levels of intracellular calcium are regulated by transport proteins that remove it from the cell. For example, the sodium-calcium exchanger uses energy from the electrochemical gradient of sodium by pumping calcium out of the cell in exchange for the entry of sodium. Additionally, the plasma membrane Ca²⁺ ATPase (PMCA) obtains energy to pump calcium out of the cell by hydrolysing adenosine triphosphate (ATP). In neurons, voltage-dependent, calcium-selective ion channels are important for synaptic transmission through the release of neurotransmitters into the synaptic cleft by vesicle fusion of synaptic vesicles.

Calcium's function in muscle contraction was found as early as 1882 by Ringer and led the way for further investigations to reveal its role as a messenger about a century later. Because its action is interconnected with cAMP, they are called synarchic messengers. Calcium can bind to several different calcium-modulated proteins such as troponin-C (the first one to be identified) or calmodulin, proteins which are necessary for promoting contraction in muscle.

Cell type	Effect
secretory cells (mostly)	↑secretion (vesicle fusion)
juxtaglomerular cell	↓secretion
Parathyroid chief cells	↓secretion
Neurons	transmission (vesicle fusion)
myocytes	contraction Activation of protein kinase C
Various	Activation of protein kinase C Further reading: Function of protein kinase C

Negative effects and pathology

Substantial decreases in extracellular Ca²⁺ ion concentrations may result in a condition known as hypocalcemic tetany, which is marked by spontaneous motor neuron discharge. Additionally, severe hypocalcemia will begin to affect aspects of blood coagulation and signal transduction.

Ca²⁺ ions can damage cells if they enter in excessive numbers (for example in the case of excitotoxicity, or over-excitation of neural circuits, which can occur in neurodegenerative diseases or after insults such as brain trauma or stroke). Excessive entry of calcium into a cell may damage it or even cause it to undergo apoptosis or death by necrosis. Calcium also acts as one of the primary regulators of osmotic stress (Osmotic shock). Chronically elevated plasma calcium (hypercalcemia) is associated with cardiac arrhythmias and decreased neuromuscular excitability. One cause of hypercalcemia is a condition known as hyperparathyroidism.

Invertebrates

Some invertebrates use calcium compounds for building their exoskeleton (shells and carapaces) or endoskeleton (echinoderm plates and poriferan calcareous spicules). Many protists also make use of calcium.

Plants

Structural roles

Ca²⁺ ions are an essential component of plant cell walls and cell membranes, and are used as cations to balance organic anions in the plant vacuole. The Ca²⁺ concentration of the vacuole may reach millimolar levels. The most striking use of Ca²⁺ ions as a structural element in plants occurs in the marine coccolithophores, which use Ca²⁺ to form the calcium carbonate plates with which they are covered.

Some plants accumulate Ca in their tissues, thus making them more firm. Calcium is stored as Ca-oxalate crystals in plastids.

Cell signaling

Ca²⁺ ions are usually kept at nanomolar levels in the cytosol of plant cells, and act in a number of signal transduction pathways.

Measuring calcium in living tissue

The total amount of Ca²⁺ present in a tissue may be measured using atomic absorption spectrometry, in which the tissue is vaporized and combusted. To measure Ca²⁺ in vivo, a range of cell permeable, calcium binding fluorescent dyes may be used.

Food sources

The USDA web site has a very complete table of calcium content (in mg) of common foods per common measures (link below).

Calcium amount in foods, 100 g:

• parmesan (cheese) = 1140 mg
• sesame seeds (unhulled) = 989 mg
• milk powder = 909 mg
• molasses = 273 mg
• hazelnuts = 250 mg
• almonds = 234 mg
• nuts = 99 mg
• ricotta (skimmed milk cheese) = 90 mg
• brown sugar = 85 mg
• lentils = 79 mg
• wheat germ = 72 mg
• pigeon pea = 62.7 mg
• egg, 1 = 54 mg
• chickpea = 53.1
• flour = 41 mg
• orange = 40 mg
• human milk = 33 mg
• Rice, white, long-grain, parboiled, enriched, cooked = 19 mg
• trout = 19 mg
• beef = 12 mg
• cod = 11 mg
• horse meat = 10 mg
• honey = 5 mg
• white sugar = 0 mg

See also

• Bone seeker

External links

• USDA national nutritional database, Calcium content of selected foods
• Calcium and vitamin D.