What is Vitamin K?

• Vitamin K is a crucial nutrient that plays a vital role in the human body. It is a family of fat-soluble vitamers that are present in various foods and are also available as dietary supplements. The primary function of vitamin K is to aid in the post-synthesis modification of certain proteins necessary for blood coagulation. This process is vital as it controls the binding of calcium in bones and other tissues. Therefore, the synthesis involves the final modification of these “Gla proteins” by an enzyme known as gamma-glutamyl carboxylase, which utilizes vitamin K as a cofactor.
• Besides its role in blood coagulation, vitamin K is also used in the liver. Here, it acts as the intermediate VKH2 to deprotonate a glutamate residue. Then, it is reprocessed into vitamin K through a vitamin K oxide intermediate. The presence of uncarboxylated proteins in the body is an indicator of a vitamin K deficiency. Carboxylation enables these proteins to bind calcium ions, which they cannot do otherwise. Without adequate vitamin K, the blood’s ability to coagulate is severely compromised, leading to uncontrolled bleeding. Moreover, research has shown that a deficiency in vitamin K may weaken bones, potentially leading to osteoporosis, and may also promote the calcification of arteries and other soft tissues.
• Chemically, the vitamin K family consists of 2-methyl-1,4-naphthoquinone derivatives. It includes two primary natural vitamers: vitamin K1 (phylloquinone) and vitamin K2 (menaquinone). Vitamin K2 further comprises several related chemical subtypes, each with different lengths of carbon side chains made of isoprenoid groups of atoms. The most studied among these are menaquinone-4 (MK-4) and menaquinone-7 (MK-7).
• Vitamin K1 is synthesized by plants and is abundantly found in green leafy vegetables due to its direct involvement in photosynthesis. It is active as a vitamin in animals, performing the classic functions of vitamin K, including its role in producing blood-clotting proteins. Animals can also convert it to vitamin K2, specifically the MK-4 variant. Furthermore, bacteria in the gut flora have the ability to convert K1 into K2. All forms of K2, excluding MK-4, can only be produced by bacteria during anaerobic respiration. It is also worth noting that Vitamin K3 (menadione), a synthetic variant of vitamin K, was previously used to treat vitamin K deficiency. However, due to its interference with the function of glutathione, it is no longer utilized in human nutrition.
• In conclusion, Vitamin K is a multifaceted nutrient with several roles in the body. It is essential for blood coagulation, bone health, and the prevention of arterial calcification. Whether sourced from plants, animals, or supplements, it is vital to ensure adequate intake for optimal health.

Definition of Vitamin K

Vitamin K is a fat-soluble vitamin essential for the synthesis of proteins involved in blood coagulation and bone health. It is naturally found in green leafy vegetables, certain animal foods, and is also produced by gut bacteria.

Properties of vitamin K

1. Fat-solubility: Vitamin K is a fat-soluble vitamin, meaning it requires dietary fat for absorption in the intestines and is stored in the liver and fatty tissues.
2. Coagulation: One of the primary roles of vitamin K is in the synthesis of proteins required for blood coagulation. Without adequate vitamin K, blood would not clot properly, leading to excessive bleeding.
3. Bone Health: Vitamin K is involved in the carboxylation of osteocalcin, a protein essential for binding calcium in bones. This property helps in maintaining bone density and strength.
4. Chemical Structure: Vitamin K compounds share a quinone ring but differ in the length and degree of saturation of the carbon tail and the number of repeating isoprene units in the side chain.
5. Variants: There are several forms of vitamin K, including vitamin K1 (phylloquinone), which is plant-derived, and vitamin K2 (menaquinone), which is produced by gut bacteria. Each form has its unique properties and functions.
6. Role in Calcium Regulation: Vitamin K helps regulate calcium deposition in the arteries and soft tissues, preventing arterial calcification and promoting cardiovascular health.
7. Synthesis by Gut Bacteria: The human gut flora can synthesize vitamin K2, contributing to the overall vitamin K status of an individual.
8. Photosynthesis: Vitamin K1 plays a role in the photosynthesis process in plants, making green leafy vegetables a rich source of this vitamin.
9. Conversion: The human body can convert vitamin K1 to vitamin K2, specifically the MK-4 variant, further diversifying its functions.
10. Toxicity: Natural forms of vitamin K have a low risk of toxicity, even at high intake levels. However, synthetic forms, like vitamin K3 (menadione), have been associated with toxicity and are no longer used for human nutrition.

Different forms of vitamin K

Vitamin K, an essential nutrient, is categorized into several distinct forms, each with its unique sources and functions. Delving into the specifics, we can identify three primary forms of Vitamin K:

1. Phylloquinone (Vitamin K1): Phylloquinone, commonly referred to as Vitamin K1, is predominantly derived from plants. It plays a crucial role in photosynthesis, which is the process by which plants convert light energy into chemical energy. Therefore, green leafy vegetables, such as spinach, kale, and broccoli, are rich sources of Vitamin K1. Besides its role in plants, Vitamin K1 is active as a vitamin in animals, emphasizing its importance in the production of blood-clotting proteins.
2. Menaquinone (Vitamin K2): Menaquinone, or Vitamin K2, is not typically obtained directly from dietary sources. Instead, it is synthesized by bacteria present in the human gut. This form of Vitamin K is particularly intriguing because of its bacterial origin. Within the category of Vitamin K2, there are several subtypes, differentiated by the lengths of their carbon side chains. The most studied subtypes include menaquinone-4 (MK-4) and menaquinone-7 (MK-7). These subtypes further highlight the complexity and diversity of Vitamin K2.
3. Menadione (Vitamin K3): Menadione represents the synthetic form of Vitamin K. It was previously used to treat Vitamin K deficiencies. However, due to its interference with the function of glutathione, a critical antioxidant in the body, its use in human nutrition has been discontinued.

In terms of their chemical structure, all these forms of Vitamin K share a ubiquinone-like structure, characterized by a quinone ring. However, they differ in the length and degree of saturation of their carbon tails and the number of repeating isoprene units in their side chains.

Chemistry of vitamin K

Diving into the intricate world of Vitamin K’s chemistry, one can discern its multifaceted nature, which is evident in its various forms and structural derivatives. Let’s delve into a detailed and sequential exploration of the chemistry of Vitamin K.

• Different Forms of Vitamin K: Vitamin K is not a singular entity but exists in multiple forms, each with its unique chemical structure and source.
  • a. Vitamin K1 (Phylloquinone): Phylloquinone, commonly referred to as Vitamin K1, is predominantly found in plants. Its presence in the plant kingdom is crucial, especially in green leafy vegetables.
  • b. Vitamin K2 (Menaquinone): Menaquinone, or Vitamin K2, has a dual origin. It is synthesized by the bacteria residing in the human intestine and is also present in animals. This dual origin adds to the complexity of Vitamin K2’s chemistry.
  • c. Vitamin K3 (Menadione): Menadione stands out as the synthetic form of Vitamin K. Unlike its natural counterparts, it is man-made and was initially developed for specific medical applications.
• Chemical Structure: All three forms of Vitamin K – K1, K2, and K3, are derivatives of naphthoquinone. This means they share a common core structure, which is the naphthoquinone ring. However, what differentiates Vitamin K1 and K2 from K3 is the presence of an isoprenoid side chain. This side chain adds to the structural complexity of the vitamins and plays a pivotal role in their functions.
• Stability and Reactivity: From a chemical standpoint, the Vitamin K family showcases stability when exposed to heat, making them resilient during cooking processes. However, their stability is compromised in the presence of certain agents and conditions. Oxidizing agents, irradiation, strong acids, and alkalies can lead to the loss of their activity. Therefore, it’s essential to store and handle them with care to preserve their efficacy.

Absorption, transport and storage of vitamin K

• Dietary Intake and Synthesis: Vitamin K can be introduced into the human body through two primary sources. Firstly, it is taken in through the diet, especially from green leafy vegetables and certain animal products. Secondly, the beneficial bacteria residing in our intestines play a pivotal role in synthesizing Vitamin K, further contributing to the body’s reserves.
• Absorption Mechanism: The absorption of Vitamin K is intricately linked with dietary fats. When ingested, Vitamin K is absorbed in tandem with fat in the form of chylomicrons. This process is not standalone and is heavily reliant on the presence of bile salts. Bile salts, produced by the liver and stored in the gallbladder, facilitate the emulsification of dietary fats, thereby aiding in the efficient absorption of fat-soluble vitamins like Vitamin K.
• Transportation: Once absorbed, Vitamin K doesn’t remain stagnant. It is actively transported throughout the body. This transportation is facilitated by Low-Density Lipoproteins (LDL), a type of cholesterol carrier. LDL ensures that Vitamin K reaches various tissues and organs where it is needed.
• Storage: The liver stands out as the primary storage site for Vitamin K. Given the liver’s role in various metabolic processes and its capacity to store vitamins, it serves as a reservoir for Vitamin K. Besides the liver, Vitamin K is also stored, albeit in smaller quantities, in other tissues within the body.

Biochemical functions of vitamin K

• Role in Blood Clotting: Vitamin K is instrumental in the blood clotting process. It facilitates the post-translational modification of certain blood clotting factors. Specifically, clotting factors II (prothrombin), VII, IX, and X are produced in the liver as inactive precursors or zymogens. Vitamin K acts as a coenzyme for the carboxylation of glutamic acid residues present in these proteins. This enzymatic reaction, catalyzed by a microsomal carboxylase, transforms glutamate (Glu) into γ-carboxyglutamate (Gla). This conversion requires the presence of Vitamin K, oxygen (O2), and carbon dioxide (CO2). Notably, the formation of γ-carboxyglutamate is inhibited by dicumarol, an anticoagulant found in spoiled sweet clover. Warfarin, a synthetic analog, can also impede Vitamin K’s action. The γ-carboxyglutamate residues in clotting factors are negatively charged, allowing them to bind with positively charged calcium ions (Ca2+). This binding forms a complex, and the mechanism of its action has been extensively studied in prothrombin. The prothrombin-Ca complex adheres to the phospholipids on the platelet membrane surface. This adherence accelerates the conversion of prothrombin into thrombin, a crucial step in the blood clotting cascade.
• Role in Bone Health: Beyond its role in coagulation, Vitamin K is also vital for bone health. It is required for the carboxylation of glutamic acid residues in osteocalcin, a calcium-binding protein found in bones. Properly carboxylated osteocalcin can bind calcium, aiding in the mineralization of the bone matrix and ensuring bone strength.
• Mechanism of Carboxylation: While the exact mechanism of carboxylation remains a subject of research, it is known that a 2,3-epoxide derivative of Vitamin K emerges as an intermediate during the reaction. Dicumarol inhibits the enzyme responsible for converting this epoxide into active Vitamin K.
• Role in Cellular Respiration: There’s evidence suggesting Vitamin K’s involvement in cellular respiration. Given its ubiquinone-like structure, Vitamin K might play a role in the electron transport chain, facilitating ATP production.

Recommended dietary allowance (RDA) of vitamin K

The Recommended Dietary Allowance (RDA) for vitamin K varies based on age, gender, and life stage. While the human gut can synthesize vitamin K with the help of bacteria, it’s essential to obtain a portion of this vitamin from dietary sources to ensure optimal health.

For adults, the suggested RDA for vitamin K is as follows:

• Men (aged 19 years and older): 120 micrograms (μg) per day
• Women (aged 19 years and older): 90 micrograms (μg) per day

It’s worth noting that pregnant and lactating women might have different requirements, and it’s always best to consult with a healthcare professional for individual needs.

It’s essential to maintain an adequate intake of vitamin K, as it plays a crucial role in blood clotting, bone health, and other vital physiological functions.

Dietary source of Vitamin K

• Vitamin K is a crucial nutrient that plays a pivotal role in various physiological functions, especially in the process of blood clotting. Therefore, understanding its dietary sources is essential for maintaining optimal health.
• Green vegetables are among the primary sources of vitamin K. Specifically, cabbage and cauliflower stand out as rich sources. Besides these, spinach, a leafy green vegetable, is also packed with this vital vitamin. Alfa-alfa and tomatoes further contribute to the dietary intake of vitamin K.
• However, vitamin K is not limited to plant-based sources. Animal-derived foods, such as egg yolk, are also enriched with this nutrient. Additionally, meat, particularly liver, contains significant amounts of vitamin K. Dairy products, including cheese and butter, are other notable sources.

Vitamin K Deficiency Syndrome

Vitamin K Deficiency Syndrome is a condition that arises when the body lacks adequate amounts of vitamin K, a crucial nutrient responsible for blood clotting and bone health. While this deficiency is relatively rare due to the widespread presence of vitamin K in various foods and its synthesis by intestinal bacteria, certain situations can lead to its onset.

Causes of Vitamin K Deficiency:

1. Antibiotic Consumption: Prolonged use of antibiotics can disrupt the intestinal bacteria that produce vitamin K.
2. Malabsorption: Conditions that hinder the absorption of vitamins, such as celiac disease or severe liver disease, can lead to a deficiency.
3. Dietary Insufficiency: A diet lacking in green leafy vegetables, fish, meat, and dairy, which are primary sources of vitamin K.
4. Excessive Loss: Conditions like chronic diarrhea can lead to the loss of vitamin K.
5. Newborns: Infants are at a higher risk because they have a sterile intestine at birth, and breast milk might not provide adequate vitamin K.

Symptoms and Consequences:

1. Impaired Blood Clotting: The primary function of vitamin K is to aid in blood clotting. A deficiency can lead to prolonged bleeding, easy bruising, and hemorrhages.
2. Osteoporosis: Vitamin K plays a role in bone health. Its deficiency can lead to weakened bones and increased risk of fractures.
3. Hemolytic Anemia and Jaundice in Infants: Excessive vitamin K in infants can affect red blood cells, leading to conditions like hemolytic anemia and jaundice.

Treatment and Prevention:

1. Dietary Intake: Consuming a balanced diet rich in green leafy vegetables, fish, meat, and dairy can ensure adequate vitamin K levels.
2. Supplementation: In cases of severe deficiency or for newborns, vitamin K supplements or injections might be prescribed.
3. Monitoring Medication: If on long-term antibiotics or other medications that affect vitamin K levels, regular monitoring and adjustments are essential.

Hypervitaminosis K

Hypervitaminosis K refers to the condition resulting from excessive intake or accumulation of vitamin K in the body. While vitamin K is essential for various bodily functions, particularly blood clotting, an overabundance can lead to adverse effects.

Causes of Hypervitaminosis K: The primary cause of Hypervitaminosis K is the administration of large doses of vitamin K. This can occur due to excessive supplementation or medical treatments that involve high doses of this vitamin.

Effects on the Body:

1. Hemolytic Anemia: One of the primary consequences of excessive vitamin K is hemolytic anemia. This condition arises when there is an accelerated breakdown of red blood cells (RBCs) in the bloodstream, leading to a reduction in the number of functioning RBCs.
2. Jaundice: Jaundice is characterized by a yellowing of the skin and eyes. It occurs when there is an accumulation of bilirubin, a yellow compound formed by the breakdown of hemoglobin in RBCs. In the context of Hypervitaminosis K, jaundice is particularly prevalent in infants.

Special Emphasis on Infants: Infants are especially susceptible to the toxic effects of excessive vitamin K. Their bodies are not equipped to handle large doses, and therefore, they are at a higher risk of developing conditions like hemolytic anemia and jaundice. It is crucial to monitor and regulate the vitamin K intake in this age group to prevent potential complications.

Antagonists of vitamin K

Antagonists of Vitamin K play a crucial role in the realm of biochemistry, particularly in the context of blood coagulation. These compounds counteract the effects of vitamin K, which is essential for blood clotting. Understanding these antagonists is vital for medical and therapeutic applications, especially in conditions where blood clotting needs to be controlled or inhibited.

Primary Antagonists of Vitamin K:

1. Heparin: Heparin is a well-known anticoagulant, which means it prevents the formation of blood clots. It acts in opposition to the effects of vitamin K, thereby inhibiting the clotting process.
2. Bishydroxy-Coumarin: This compound also functions as an anticoagulant, counteracting the clot-promoting effects of vitamin K.
3. Salicylates: Salicylates are another group of compounds that act as antagonists to vitamin K. They interfere with the clotting process by opposing the actions of vitamin K.
4. Dicumarol: Dicumarol is particularly interesting because it shares a structural similarity with vitamin K. Due to this resemblance, dicumarol acts as a competitive inhibitor in the synthesis of active prothrombin, a protein essential for blood clotting.

Mechanism of Action: The antagonistic action of these compounds, especially dicumarol, is rooted in their ability to interfere with the synthesis of active prothrombin. Prothrombin is a precursor to thrombin, an enzyme that plays a pivotal role in the blood clotting cascade. By inhibiting the synthesis of prothrombin, these antagonists effectively disrupt the clotting process.