The Importance of Calcium Ions in Biological Processes

By V. Sai Kalyani

Bioinorganic chemistry of Calcium


Calcium is a mineral that we come across frequently, especially in relation to milk and its ability to strengthen bones, as we are often told by our elders. However, there is much more to calcium than just that. Our blog article on the bioinorganic chemistry of calcium takes a detailed look at the role of calcium ions in biological processes, providing a comprehensive exploration of its significance.


Table of contents

  1. Introduction to Calcium ions

  2. Biological importance of Calcium ions

  3. Role of Calcium ions in blood clotting

    1. Blood Coagulation Cascade

    2. Formation of prothrombin activator

    3. Conversion of Prothrombin to Thrombin

    4. Conversion of Fibrinogen into Fibrin

  4. Main sources of Calcium

  5. Mechanism of calcium absorption by human body

  6. Factors affecting the calcium absorption

  7. Adverse effects of Calcium ions on biological system

    1. Hypocalcemia

    2. Hypercalcemia

  8. FAQs on bioinorganic chemistry of calcium

  9. MCQs on bioinorganic chemistry of calcium


Introduction of Calcium ions


Calcium, an essential bioinorganic element, is present in the human body with an average concentration ranging from 100 to 170 grams. It serves as a vital component of bones and teeth, existing as a double salt of calcium and phosphate.

The majority of calcium, approximately 99%, is found in the skeletal system, while only a small fraction, about 0.5%, is present in soft tissues.

In the plasma, calcium exists in three primary forms:

  •  Diffusible ionized calcium. It is physiologically active form of calcium
  •  Protein bound calcium. Albumin is the major protein with which calcium is bound
  • Calcium in complexes with organic acids

It shows dietary sources and the biological importance of Calcium.


Biological importance of Ca2+ ions


1. Ca2+ plays a crucial role in regulating heart rhythm.

2. In bones and teeth, Ca2+ ions are present as apatite (Ca3(PO4)2), while teeth enamel contains fluorapatite [3{Ca3 (PO4)2}.CaF2].

3. Calcium is recommended as a treatment for specific cases of cardiac arrest caused by hyperkalemia, hypocalcemia, or calcium-channel blocker overdose.

4. Ca2+ ions function as messengers in hormonal action and contribute to maintaining homeostasis and the level of parathyroid hormone.

5. Ca2+ ions are crucial for initiating nerve impulses and activating choline during nerve transmission.

6. Ca2+ ions play a significant role in stabilizing protein structures.

7. Ca2+ ions act as cofactors for several enzymes, including protein kinase, lipase, adenylate cyclase, and more.

8. Ca2+ ions form complexes with K+ and Mg2+ ions, which are essential for processes like muscle contraction and glycolysis.

9. Ca2+ ions exhibit a strong affinity for water, proteins, and enzymes, primarily due to their higher concentration in extracellular fluids compared to intracellular fluids.


Role of Calcium ions in blood clotting


Blood coagulation, also known as clotting, is a crucial process that prevents excessive blood loss during injuries or trauma.

When a wound occurs, blood clotting mechanisms are triggered to stop the flow of blood. The resulting clot, or coagulum, forms a network of fibrin threads that trap deformed and dead formed elements such as erythrocytes, leukocytes, and platelets.

Prothrombin, an inactive form of thrombin found in plasma, is converted to active thrombin by thrombokinase. Thrombin, in turn, activates fibrinogen to form fibrin, contributing to the formation of the blood clot. These various clotting factors play essential roles in the process of blood coagulation.

Platelets or thrombocytes release several factors in response to an injury, initiating the cascade of blood clotting. Calcium ions play a vital role in the process of blood coagulation.

Blood coagulation involves a series of reactions triggered by the activation of clotting factors. There are a total of 13 clotting factors involved in the process of blood clotting.


  1. Factor I Fibrinogen
  2. Factor II Prothrombin
  3. Factor III Thromboplastin
  4. Factor IV Calcium Factor
  5. Factor V Labile factor (Proaccelerin)
  6. Factor VI Unassigned
  7. Factor VII Stable factor
  8. Factor VIII Antihemophilic factor
  9. Factor IX Christmas factor            
  10. Factor X Stuart-Prower factor
  11. Factor XI Plasma thromboplastin antecedent
  12. Factor XII Hageman factor
  13. Factor XIII Fibrin-stabilising factor


Blood Coagulation Cascade


Coagulation is a sequential series of enzyme-catalyzed reactions, where the activation of one factor triggers the activation of subsequent factors.

The blood coagulation cascade involves three primary steps:

➤ Formation of prothrombin activator:

The process begins with the activation of specific factors, usually triggered by tissue injury or exposure to substances that initiate coagulation.

➤ Conversion of prothrombin to thrombin:

The activated factors further stimulate the activation of more factors, leading to the amplification of the coagulation response.

➤ Conversion of fibrinogen into fibrin

This step involves the formation of a fibrin clot through the activation of fibrinogen, which is converted into fibrin by the action of activated thrombin. The fibrin clot reinforces the platelet plug and stabilizes the clot at the site of injury.


Formation of prothrombin activator


The formation of prothrombin activator is an essential step in the secondary hemostasis blood coagulation cascade. It involves two pathways: the extrinsic pathway and the intrinsic pathway.

Extrinsic Coagulation Pathway

Also known as the tissue factor pathway, it is a shorter pathway. Damaged vascular walls release tissue factors or tissue thromboplastins, which activate factor VII to VIIa. Factor VIIa, in the presence of Ca2+, further activates factor X to Xa.

Intrinsic Coagulation Pathway

The intrinsic pathway, a longer pathway in secondary hemostasis, begins with the exposure of blood to collagen from the damaged endothelium. This activation leads to the activation of plasma factor XII to XIIa.

XIIa, a serine protease, then activates factor XI to XIa. In the presence of Ca2+ ions, XIa activates factor IX to IXa.

Factor IXa, along with factor VIIIa, Ca2+, and phospholipids, activates factor X to Xa.

Common Pathway

The formation of the prothrombin activator occurs when factor Xa, factor V, phospholipids, and calcium ions come together. This marks the initiation of the common pathway, which is shared by both the extrinsic and intrinsic pathways in the coagulation process.


Conversion of Prothrombin to Thrombin


Prothrombin, also known as factor II, is a plasma protein and exists as an inactive enzyme called thrombin. The synthesis of prothrombin in the liver requires vitamin K. 

The prothrombin activator formed in the previous step facilitates the conversion of prothrombin to thrombin. 

Thrombin, being a proteolytic enzyme, also enhances its own production by converting prothrombin to thrombin. Additionally, thrombin activates factors VIII, V, and XIII, promoting the formation of the prothrombin activator.

                                       Ca2+

Prothrombin       →       Thrombin

                     Thromboplastin


Conversion of Fibrinogen into Fibrin


Thrombin plays a crucial role in the conversion of fibrinogen, also known as factor I, into fibrin. Thrombin acts on fibrinogen and forms fibrin monomers, which then undergo polymerization to create long fibrin threads.

These threads are further stabilized by the action of factor XIII, also known as fibrin stabilizing factor. Thrombin activates the fibrin stabilizing factor, converting it into its active form, factor XIIIa. 

Factor XIIIa facilitates the cross-linking between fibrin threads in the presence of Ca2+, thereby providing stability to the fibrin meshwork. The formed elements are trapped within this fibrin meshwork, leading to the formation of a solid mass known as a clot.

                        Thrombin

Fibrinogen     →    Fibrin (Clot)


Main sources of Calcium


Calcium is a vital mineral that is widely distributed in various food sources. It can be found in foods such as milk, cheese, egg yolk, beans, lentils, nuts, figs, cabbage, and cauliflower, among others. These food substances serve as excellent dietary sources of calcium, ensuring its availability for the human body.

The daily recommended intake of calcium varies depending on age and life stage. For adult individuals, a daily intake of 800 mg of calcium is generally recommended to support the smooth functioning of biological processes that rely on calcium. This includes maintaining proper bone health, supporting muscle function, and aiding in nerve transmission.

Pregnant women and growing children have increased calcium needs due to the demands of pregnancy and growth. It is recommended for them to consume approximately 1,500 mg of calcium per day to support the development of strong bones and teeth, as well as to meet the calcium requirements necessary for proper physiological processes.

By incorporating calcium-rich foods into their diet and meeting the recommended daily intake, individuals can ensure they have an adequate supply of calcium to support their overall health and well-being.


Mechanism of calcium absorption by human body


The human body possesses a well-regulated mechanism for the absorption of calcium. The absorption process primarily occurs in the small intestine and involves several intricate steps.

Calcium enters the body through dietary sources, particularly in the form of neutral phosphates found in food. Within the acidic environment of the digestive tract, these calcium phosphates undergo a transformation into soluble acid phosphates like CaHPO4 and Ca (H2PO4)2. These soluble acid phosphates are then absorbed in the intestine and enter the bloodstream.

In a healthy adult, approximately 40% of dietary calcium is successfully absorbed. However, as individuals age beyond 60 years, there is a gradual decrease in the intestinal absorption of calcium.


Factors affecting the calcium absorption


The absorption of calcium differs from that of sodium (Na) and potassium (K) as it is not readily absorbed. Several factors that affect the absorption of calcium are outlined below:


  • The presence of an acidic pH in the intestinal environment facilitates calcium absorption.
  • A diet rich in protein promotes the absorption of calcium.
  • Organic acids produced through the microbial fermentation of sugars in the gut enhance calcium absorption.
  • Vitamin D plays a crucial role in promoting calcium absorption in the body.


On the other hand, certain factors can hinder the absorption of calcium:

Cereals containing phytic acid, food items with high oxalate content, excessive intake of magnesium, phosphates, and a high-fiber diet can lead to the formation of insoluble calcium salts, reducing calcium absorption.


Adverse effects of Calcium ions on biological system


When the concentration of calcium exceeds the normal level in the human body, it is referred to as hypercalcemia. Conversely, if the concentration of calcium falls below the normal level, it is known as hypocalcemia.


Hypocalcemia


A deficiency of calcium results in weakened bones and teeth, leading to their softening and distortion. In children, the deficiency of calcium, vitamin D, and phosphorus can cause rickets, a condition characterized by retarded growth and deformed bones such as bowlegs, enlarged joints, and knock knees. In adults, calcium deficiency can lead to osteoporosis, which involves the loss of bone mass and an increased risk of bone fractures. Insufficient calcium levels can also prolong blood clotting time during injuries and impair nerve function.


Hypercalcemia


Despite excess calcium being excreted as water-soluble calcium salts through urine, hypercalcemia can still have detrimental effects on the human body. It can contribute to the formation of kidney and gall bladder stones, a condition known as lithogenesis. Excessive calcium deposits in the body can lead to kidney failure, Addison's disease, and thyrotoxicosis. Additionally, when calcium concentration is elevated, it may deposit as calcium carbonate and calcium phosphate at the ends of bone joints and teeth.


FAQs on bioinorganic chemistry of calcium


Write any two biological functions of Calcium?


Calcium is essential for the strengthening and hardening of teeth and bones. In teeth and bones, calcium exists in the form of calcium phosphate and calcium carbonate, which provide structural support and contribute to their overall strength.

Calcium plays a crucial role in the activation of various enzymes within the body. Enzymes such as ATPase and succinic dehydrogenase require calcium ions to become active and carry out their specific biochemical reactions. Calcium acts as a cofactor, facilitating the proper functioning of these enzymes and contributing to various metabolic processes in the body.


What are the primary dietary sources of calcium?


Dairy products such as milk and cheese serve as the main dietary sources of calcium, meeting approximately 65-75% of the body's calcium requirements. Additionally, eggs, fish, and meat contribute about 5-10% of the necessary calcium intake. Apart from dairy and animal-based products, non-dairy sources like nuts, beans, lentils, and figs, as well as certain vegetables like cabbage and cauliflower, provide smaller amounts of calcium.

Some other sources of dietary calcium include dark green leafy vegetables such as kale, collard greens, and spinach and calcium-fortified foods such as breakfast cereals, orange juice, and soy milk.

Calcium-rich foods are also available in supplement form, such as calcium carbonate and calcium citrate.


What factors contribute to hypocalcemia in humans?


Low intake of dairy products and animal protein can contribute to the development of hypocalcemia. These food sources are rich in calcium and essential for maintaining adequate levels of calcium in the body.

In addition, certain conditions such as sprue syndrome and intestinal malabsorption can interfere with the absorption of calcium in the digestive tract, leading to insufficient supply of calcium to the body. These physiological illnesses disrupt the normal absorption process and can result in lower calcium levels.


MCQs on bioinorganic chemistry of Calcium


1. How much calcium that a pregnant women should intake per day?

  1. 1000 grams

  2. 1500 grams

  3. 1200 grams

  4. 850 grams

Answer: 1500 grams

2. What is the metal ion that plays a vital role in blood clotting?

  1. Magnesium

  2. Calcium

  3. Molybdenum

  4. Copper

Answer: Calcium

3. Rickets disease is caused by the deficiency of ____________________

  1. Manganese, Phospohorous, Vitamin-D

  2. Vitamin-D, Magnesium, Calcium

  3. Calcium, Phosphorous, Vitamin-D

  4. Calcium, Cobalt, Vitamin-D

Answer: Calcium, Phosphorous, Vitamin-D

4. Excess calcium concentration in human body leads to______________

  1. Hypercalcemia

  2. Hypocalcemia

  3. Calcemia

  4. Hyperkalemia

Answer: Hypercalcemia

5. Which of the following factor favours the calcium absorption in human body?

  1. Acidic pH of intestinal milieu

  2. High protein diet

  3. Vitamin-D

  4. All the above

Answer: All the above