12.5 Vitamin K

Vitamin K

There are 3 forms of vitamin K. Phylloquinone (K1), the plant form of vitamin K, is the primary dietary form of vitamin K and found in green leafy vegetables, broccoli, Brussels sprouts, and asparagus are foods that are good sources of phylloquinone1. Another form of vitamin K, menaquinone (K2), is synthesized by bacteria in the colon. Menaquinone comprises ~10% of absorbed vitamin K every day and can also be found in small amounts in animal products. Its structure is shown below2. The third form, a synthetic form of vitamin K, is menadione (K3).

Vitamin K is absorbed like other fat-soluble substances. Approximately 80% of phylloquinone and menaquinone are incorporated into chylomicrons and stored primarily in the liver1,3. Once metabolized, vitamin K is primarily excreted via bile in the feces, with a lesser amount excreted in urine3.

For more information on vitamin K, see the Required Web Link below.

Required Web LinkVitamin K Fact Sheet for Health Professionals

Subsections:

• 12.51 Vitamin K Functions
• 12.52 Vitamin K Deficiency & Toxicity

References & Links

• McGuire M, Beerman KA. (2011) Nutritional sciences: From fundamentals to food. Belmont, CA: Wadsworth Cengage Learning.
• Byrd-Bredbenner C, Moe G, Beshgetoor D, Berning J. (2009) Wardlaw’s perspectives in nutrition. New York, NY: McGraw-Hill.
• Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.

Vitamin K Functions

Vitamin K is a cofactor for carboxylation reactions that add a CO₂ to the amino acid, glutamic acid (glutamate), in certain proteins. The enzyme, gamma-glutamyl carboxylase, uses a vitamin K cofactor to convert glutamic acid to gamma-carboxyglutamic acid (Gla). Gla proteins are those that contain glutamic acid(s) that have been converted to gamma-carboxyglutamic acid(s). The formation of Gla proteins allows the 2 positive charges of calcium to bind between the 2 negative charges on the carboxylic acid groups (COO-) in the Gla. The binding of calcium activates these proteins1-3.

Figure 12.512 Gamma-glutamyl carboxylase converts glutamic acid to gamma-carboxyglutamic acid (Gla).

Gla proteins are important in blood clotting. Blood clotting occurs through a cascade of events, as shown in the following 2 videos. The animation below gives an overview of blood clotting, the video is a fun depiction of the blood clotting cascade.

Web LinksHemostasis AnimationVideo: The Clotting Cascade (1:20)

If these proteins within the blood clotting cascade are not activated to Gla, the cascade does not proceed as normal, leading to impaired blood clotting. After being used as a cofactor by gamma-glutamyl carboxylase to produce a Gla protein, vitamin K becomes vitamin K epoxide. Vitamin K epoxide needs to be converted back to vitamin K to serve as a cofactor again.

Warfarin (Coumadin) and dicumarol are a couple of blood thinning drugs that inhibit this regeneration of vitamin K. This reduces the amount of Gla in the blood clotting proteins, thus reducing the clotting response. The structure of warfarin and dicumarol are shown in Figure 12.514.

Figure 12.514 Structure of warfarin5

Figure 12.515 Structure of dicumarol6

The following coumadin rap song video gives further information on warfarin.

Web LinkVideo: Coumadin Rap Song (3:44)

Vitamin K may also be important for bone health. There are 3 Gla proteins found in bone: osteocalcin, matrix Gla protein (MGP), and protein S4. Osteocalcin is a major bone protein, constituting 15-20% of all non-collagen proteins in bone. However, overall, the function of these 3 proteins in bone is not known2,3. Some research suggests that higher vitamin K status or intake decreases bone loss, but it is still not clear whether vitamin K truly is important for bone health7.

References & Links

• Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.
• Byrd-Bredbenner C, Moe G, Beshgetoor D, Berning J. (2009) Wardlaw’s perspectives in nutrition. New York, NY: McGraw-Hill.
• McGuire M, Beerman KA. (2011) Nutritional sciences: From fundamentals to food. Belmont, CA: Wadsworth Cengage Learning.

• Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, editors. (2006) Modern nutrition in health and disease. Baltimore, MD: Lippincott Williams & Wilkins.
• http://en.wikipedia.org/wiki/File:Warfarin.svg
• http://en.wikipedia.org/wiki/File:Dicumarol.svg
• Shea MK, Booth S. (2008) Update on the role of vitamin K in skeletal health. Nutr Rev 66(10): 549-557.

Videos

Hemostasis Animation- http://www.mhhe.com/biosci/esp/2002_general/Esp/folder_structure/tr/m1/s7/trm1s7_3.ht m

The Clotting Cascade – https://www.youtube.com/watch?v=NJm4DE-tVuY&feature=related Coumadin Rap Song – http://www.youtube.com/watch?v=Mfk05IFfW48&feature=watch_response

Vitamin K Deficiency & Toxicity

Vitamin K deficiency is rare, but can occur in newborn infants. They are at higher risk, because there is poor transfer of vitamin K across the placental barrier, their gastrointestinal tracts do not contain vitamin K producing bacteria, and breast milk is generally low in vitamin K1. As a result, it is recommended (and widely practiced) that all infants receive a vitamin K injection within 6 hours of birth2.

Prolonged antibiotic treatment (which kills bacteria in the gastrointestinal tract) and lipid absorption problems can also lead to vitamin K deficiency3. Vitamin K deficient individuals have an increased risk of bleeding or hemorrhage. Remember that high levels of vitamin E intake can also interfere with vitamin K’s blood clotting function. It is believed that a vitamin E metabolite, with similar structure to the vitamin K quinones, antagonizes the action of vitamin K.

Phylloquinone and menaquinone have no reported toxicities. However, menadione can cause liver damage1.

References & Links

• Gropper SS, Smith JL, Groff JL. (2008) Advanced nutrition and human metabolism. Belmont, CA: Wadsworth Publishing.
• Byrd-Bredbenner C, Moe G, Beshgetoor D, Berning J. (2009) Wardlaw’s perspectives in nutrition. New York, NY: McGraw-Hill.
• McGuire M, Beerman KA. (2011) Nutritional sciences: From fundamentals to food. Belmont, CA: Wadsworth Cengage Learning.