Phylloquinone and related compounds vitamin K

The structure of vitamin K is characterized by methylnaphthoquinone rings with a side chain at position 3. It exists naturally in two forms phylloquinone (vitamin Kj 6.13) occurs only in plants, while menaquinones (vitamin K2 6.14) are a family of compounds with a side chain consisting of between 1 and 14 isoprene units. Menaquinones are synthesized only by bacteria (which inhabit the human gastrointestinal tract and thus provide some of the vitamin K required by the body). Menadione (vitamin K3 6.15) is a synthetic compound with vitamin K activity. Unlike Kj and Kj, menadione is water soluble and is not active until it is alkylated in vivo. 

The physiological role of vitamin K is in blood clotting and is essential for the synthesis of at least four of the proteins (including prothrombin) involved in this process. Vitamin K also plays a role in the synthesis of a protein (osteocalcin) in bone. Vitamin K deficiency is rare but can result from impaired absorption of fat. Vitamin K levels in the body are also reduced if the intestinal flora is killed (e.g. by antibiotics). Vitamin K toxicity is rare but can be caused by excessive intake of vitamin K supplements. Symptoms include erythrocyte haemolysis, jaundice, brain damage and reduced effectiveness of anticoagulants. 

The RDAs for vitamin K for people aged 19-24 years are 70 pg and 60/igday for men and women, respectively. Corresponding values for 

Whole cows milk contains 0.4-1.8/ig vitamin K per 100 g while human milk contains about 0.2/ig per 100 g. Human colostrum contains higher concentrations of vitamin K, which are necessary since bacteria capable of synthesizing vitamin K take time to become established in the intestine of the neonate. Irradiation under anerobic and apolar conditions can result in cis-trans isomerization, resulting in loss of activity since only the trans isomer has vitamin K activity. However, unit operations in dairy processing are unlikely to have an effect on the stability of this nutrient. 

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FIGURE 9.24 Wamin K and related compounds. Vitamin Kj, also called phylloquinone, is 2-methyl-3-phytyl-l,4-naphtiioquinone. Vitamin K2, also called menaquinone, occurs naturally with a polyisoprenoid tail containing from 5 to 13 isoprenoid units. The figure shows menaquinone-7 (MK-7), which contains a seven-isoprenoid-unit tail. Studies of human Uver have revealed that MK-7, MK-8, MK-10, MK-11, and MK-12 account for most of the vitamin K in this tissue, while phylloquinone accounts for about 10% of the vitamin K (Suttie, 1995). Vitamin K3 is a synthetic version of the vitamin. 

There are different physiological forms known as vitamins K, namely vitamin Kj (phylloquinone, phytonadi-one) and vitamin K2 (farnoquinone). There are active anologs and related compounds knows as vitamins K, namely menadiol diphosphate, menadione (vitamin K3 ), menadione bisulfite, phthiocol, synkayvite, menadiol (vitamin K4), menaquinone-n (MK-n), ubiquinone (Q-n), and plastoquinone (PQ-n) [3]. 

Another important family of quinones, related in structure to those already discussed, are the vitamins K (Fig. 15-24, Box 15-F). These occur naturally as two families. The vitamins K, (phylloquinones) have only one double bond in the side chain and that is in the prenyl unit closest to the ring. This suggests again the possibility of chromanol formation. In the vitamin K2 (menaquinone) series, a double bond is present in each of the prenyl units. A synthetic compound menadione completely lacks the polyprenyl side chain and bears a hydrogen in the corresponding position on the ring. Nevertheless, menadione serves as a synthetic vitamin K, apparently because it can be converted in the body to forms containing polyprenyl side chains. 

The mechanism of intestinal absorption of compounds with vitamin K activity varies with their solubility. In the presence of bile salts, phylloquinone and the menaquinones are adequately absorbed from the intestine, almost entirely by way of the lymph. Phylloquinone is absorbed by an energy-dependent, saturable process in proximal portions of the small intestine menaquinones are absorbed by diffusion in the distal portions of the small intestine and in the colon. Following absorption, phylloquinone is incorporated into chylomicrons in close association with triglycerides and lipoproteins. The extremely low phylloquinone levels in newborns may be partly related to very low plasma lipoprotein concentrations at birth and may lead to an underestimation of vitamin K tissue stores. Absorbed phylloquinone and menaquinones are concentrated in the liver, but the concentration of phylloquinone declines rapidly. Menaquinones, produced in the lower bowel, are less biologically active than phylloquinone due to their long side chain. Very little vitamin K accumulates in other tissues. 

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