Intestinal Absorption of Vitamin K: Cellular and Molecular Mechanisms




Abstract


The lipid-soluble Vitamin K plays an essential role in facilitating blood coagulation by activating clotting factors; it also plays a role in signal transduction, cell proliferation, and in bone and cartilage metabolism. Vitamin K is widely distributed in diet, and is also produced by the normal gut microbiota. Humans cannot synthesize Vitamin K endogenously, and thus, must obtain it from exogenous sources via intestinal absorption. Absorption of dietary Vitamin K in the small intestine is carrier-mediated and energy-dependent process, while absorption of the microbiota-generated Vitamin K is via passive diffusion. A role for the Niemann-Pick C1-like 1 (NPC1L1) protein as well as for the scavenger receptor class B-type I (SR-BI) and the cluster-determinant 36 (CD36) in intestinal Vitamin K absorption has been reported. However, little is currently known about the relative contribution of these different systems toward overall Vitamin K absorption process in health and disease and needs further investigations.




Keywords

Vitamin K, Intestinal absorption, Transport mechanism

 




Abbreviations


CD36


cluster determinant 36


GGCX


γ-carboxyglutamyl carboxylase


MK


Vitamin K 2 [represented by members of the menaquinones (MK) family]


NPC1L1


Niemann-Pick C1-like 1


Phylloquinone


Vitamin K 1


SR-BI


scavenger receptor class B-type I


UBIAD1


UbiA prenyltransferase-containing domain 1




Acknowledgment


Supported by grants from the Department of Veterans Affairs and the National Institutes of Health (DK56061, DK58057 and AA 018071).





Metabolic Role and Effect of Deficiency


Vitamin K ( Fig. 53.1 ) refers to a group of fat-soluble molecules that are known for their essential role in facilitating blood coagulation by activating clotting factors (e.g., prothrombin and factors II, VII, IX, and X) in the liver. Antagonizing this effect of Vitamin K with the use drugs such as warfarin is the basis for clinical use of such medications in the prevention of thromboembolism in humans. At the metabolic level, Vitamin K serves as a cofactor for one microsomal enzyme, γ-carboxyglutamyl carboxylase (GGCX), which catalyzes the conversion of peptide-bound glutamate residues of specific proteins to γ-carboxyglutamate. Such conversion provides sites for calcium binding to the particular protein. Because the Vitamin K-dependent proteins (e.g., the blood-clotting factors, osteocalcin, and matrix γ-carboxyglutamic acid) serve in a variety of cellular reactions and are expressed in a variety of tissues, the vitamin assumes other functions beside blood coagulation including bone and cartilage metabolism, signal transduction, and cell proliferation. Vitamin K also appears to have physiological roles that are not related to its function as a cofactor for GGCX. From the above, it becomes clear that optimizing body homeostasis of Vitamin K brings about clear health benefits to humans (e.g., it decreases the risk of certain cardiovascular diseases and osteoporosis) . Vitamin K deficiency in normal human subjects is rare due to the ubiquitous distribution of the vitamin in the diet, its synthesis by normal gut microbiota, and the fact that only small quantities of the vitamin is required to serve as a cofactor in γ-glutamyl carboxylation reactions. The recent recognition of ability of many cell types to regenerate Vitamin K from its epoxide metabolite, via what is known as the Vitamin K cycle, also contributes to the low requirement of the vitamin as a cofactor (reviewed in Ref. ). Suboptimal/deficient levels of Vitamin K, however, do occur in patients with fat malabsorption disorders (e.g., pancreatic insufficiency, biliary tract disease, cystic fibrosis, bacterial overgrowth in the small intestine, chronic use of bile acid resins such as cholestyramine, short bowel syndrome), those receiving Vitamin K antagonists (e.g., warfarin), and those with inadequate body stores (like newborn infants, where IM administration of the vitamin is recommended to prevent hemorrhagic disease of the newborn). Suboptimal levels of Vitamin K have also been reported in individuals on broad-spectrum antibiotics for long periods (due to disturbance in gut microbiota). The adequate intake level for Vitamin K is set at 90 μg/day for women and 120 μg/day for men.




Fig. 53.1


Chemical structure of Vitamin K compounds.


Like many other vitamins, the human body cannot synthesize Vitamin K endogenously, and therefore, must obtain the vitamin from exogenous sources via intestinal absorption. Thus, the intestine plays an important role in regulating and maintaining normal body level of the vitamin. The human intestine is exposed to two sources of Vitamin K: a dietary source and a microbiota source. Vitamin K exists in two major forms: Vitamin K 1 (phylloquinone) and Vitamin K 2 [represented by members of the menaquinones (MK) family]. All Vitamin K compounds share a common structure of 2-methyl-1,4-naphthoquinone ring (called menadione; Fig. 53.1 ) to which a hydrophobic polyisoprenoid side chain of varying length and degree of saturation is attached at position 3 of the ring. Vitamin K1 represents the majority (between 75% and 90%) of Vitamin K in Western diets, and is found in leafy green vegetables and in certain vegetable oils, such as soybean and olive oil. Vitamin K2 forms are found in liver and fermented products (e.g., cheese) ; they are also the forms generated by the gut microbiota. Members of the Vitamin K2 family are named according to the number of prenyl units present in the side chain, with MK-6, -7, -8, -10, and -11 forms representing the major forms produced by the gut microbiota. Bioavailability of the gut microbiota-generated Vitamin K2 forms has been documented and their contribution to human nutrition is established.

Only gold members can continue reading. Log In or Register to continue

Apr 21, 2019 | Posted by in ABDOMINAL MEDICINE | Comments Off on Intestinal Absorption of Vitamin K: Cellular and Molecular Mechanisms
Premium Wordpress Themes by UFO Themes