Summary
Vitamin Ok obtained its identify from the truth that it’s required for regular blood coagulation, and through about half a century it was believed that hemostasis was the one metabolic course of through which vitamin Ok is concerned. This view is out of date now. For the reason that identification of Gla as the results of vitamin Ok motion, it turned doable to seek for vitamin Ok-dependent proteins on the premise of their amino acid construction: every protein through which gammacarboxyglutamate, typically known as Gla, is discovered accommodates the fingerprint of vitamin Ok motion throughout its biosynthesis (1). On this manner all kinds of proteins had been discovered starting from osteocalcin (essentially the most ample non-collagenous protein in bone), to matrix Gla-protein (MGP, the potent calcification inhibitor in our arteries), and the growth-arrest sequence-6 protein (Gas6, a protein concerned in cell development regulation). Whereas the proteins concerned in blood coagulation invariably are synthesized within the liver, the newly found Gla-proteins have key features in different metabolic processes and are synthesized in all kinds of tissues. An summary of the varied Gla-proteins and their features (so far as they’re recognized) is given in Desk 1.
The molecular perform of vitamin Ok is exactly recognized: it serves as a cofactor for the enzyme gammaglutamate carboxylase (GGCX), which is discovered within the endoplasmic reticulum of all kinds of mammalian cells and that catalyzes the conversion of the amino acid glutamate into Gla. The oxidation of vitamin Ok hydroquinone supplies the vitality required for this carboxylation response. All Gla-proteins are secretory proteins discovered within the extracellular matrix or in physique fluids. Gla-residues kind sturdy calcium-binding teams within the proteins to which they’re hooked up and in all circumstances through which their perform is understood the Gla-residues are important for the perform of those proteins (2).
All Gla-proteins recognized as we speak comprise a number of Gla-residues per molecule starting from three within the bone Gla-protein osteocalcin to 10 in prothrombin and as a lot as 16 in Gla-rich protein (GRP). The place of the Gla-residues throughout the respective proteins is well-defined, however within the case of vitamin Ok insufficiency under-carboxylated and even uncarboxylated Gla-proteins are synthesized. Such proteins lack organic exercise and could also be considered biomarkers for vitamin Ok insufficiency. Probably the most correct definition of vitamin Ok is due to this fact: a compound (or a gaggle of compounds) catalyzing the carboxylation of protein-bound glutamate by serving as a coenzyme for the GGCX enzyme.
Vitamin Ok in our food plan
Vitamin Ok shouldn’t be a single compound, however a gaggle identify for a household of associated buildings that every one share a methylated naphthoquinone ring system substituted with a variable aliphatic facet chain (3). In phylloquinone (vitamin K1) the facet chain consists of 4 isoprenoid residues, the final three of that are saturated. Menaquinones (vitamin K2) kind a sub-family through which the size of the facet chain could vary from 1 to 13 isoprene residues, all of that are unsaturated. The varied menaquinones are typically denoted as MK-n, the place n represents the variety of isoprene residues within the aliphatic facet chain. Vital menaquinones are the brief chain MK-4 and the lengthy chain menaquinones MK-7, MK-8, MK-9, and MK-10 that every one happen within the human food plan, whereas small quantities of MK-6 have additionally been present in numerous meals.
Vitamin K1 is shaped in crops and vital sources in our food plan are inexperienced leafy greens reminiscent of spinach, broccoli, Brussels sprouts, and kale. It’s positioned within the chloroplasts the place it types a part of the electron transport system and about 90% of the entire vitamin Ok within the western food plan is shaped by K1. Menaquinones (besides MK-4) are of microbial origin and comparatively excessive concentrations are solely present in just a few meals objects. Natto is a conventional Japanese meals consisting of fermented soybeans; Bacillus subtilis natto is the supply of vitamin K2 (nearly solely MK-7) on this meals, which can comprise as much as 1100 µg of K2 per 100 grams of meals. The sharp style of natto is very appreciated in Japan however not in western societies. Different vitamin K2-producing micro organism are lactic acid micro organism (primarily MK-8 and MK-9) and propionic acid micro organism (primarily MK-10). Each strains are used within the manufacturing of cheese and curd cheese, which kind the richest sources of vitamin K2 in Europe and Northern America. Small quantities of MK-4 may be obtained from animal merchandise reminiscent of meat and egg yolk; the MK-4 originates from menadione (2-methyl naphthoquinone), which is added to the animal meals, and which is transformed into MK-4 after uptake within the blood stream. It has additionally been reported that flatfish and eel, dwelling on the backside of the seas and lakes, comprise small quantities of K2 that had been regarded to originate from the micro organism in decomposing natural materials serving as their meals.
Pharmacokinetics and efficacy of various types of vitamin Ok
As will be understood from their molecular buildings, the lipophylicity of the varied Ok-vitamins differs considerably with rising fat-solubility at rising facet chain size. Whereas menadione (no facet chain) is water-soluble, phylloquinone and MK-4 are mildly hydrophobic, and the lengthy chain menaquinones (MK-7 and better) are solely soluble in apolar natural solvents like hexane.
Intestinal uptake of Ok-vitamins is considerably affected by the meals matrix through which it’s embedded. Vitamin K1, as an example, is tightly certain to the chloroplasts of inexperienced greens from which it’s hardly liberated within the digestive tract. Uptake from cooked spinach and broccoli is 5–10% solely, which may double by concomitant fats consumption. K2-vitamins, alternatively, are primarily discovered within the fats fraction of dairy and are absorbed nearly utterly (4). From these knowledge it may be understood that, though 90% of our vitamin Ok consumption consists of K1, phylloquinone and menaquinones contribute roughly equally to the human vitamin Ok standing. Additionally purified types of vitamin Ok that could be current in meals dietary supplements and practical meals are readily absorbed, particularly together with a meal (4).
After intestinal uptake, all Ok-vitamins are integrated in triglyceride-rich lipoproteins and transported to the liver. A exceptional distinction is that almost all of vitamin K1 is retained by the liver for use for clotting issue synthesis, whereas K2-vitamins are integrated into low density lipoproteins (LDL) and let out within the blood stream (5). On this manner extrahepatic tissues together with bone and arteries are equipped with the vitamin Ok required for extrahepatic Gla-protein carboxylation. The totally different transport programs for nutritional vitamins K1 and K2 kind the premise for his or her totally different goal tissues. Since no particular receptors for vitamin Ok have been found on the outer membrane of assorted cells, it’s seemingly that LDL-bound vitamin Ok is taken up by the cells by way of the LDL-receptors and subsequently dissolves within the membrane buildings of the cells, notably the endoplasmic reticulum the place it shows its cofactor perform.
One other distinction between K1 and MK-4 on the one hand and the long-chain menaquinones alternatively is their organic half-life time within the blood stream (5). Whereas K1 and MK-4 usually exhibit half-life instances of 1–1.5 hour, lengthy chain menaquinones reminiscent of MK-7 and MK-9 are characterised by half life instances of a number of days (4, 6). This was demonstrated in a volunteer experiment through which equal quantities of K1 and MK-7 had been ingested; it resulted that K1 had nearly utterly disappeared after 8 hours, whereas MK-7 (nearly solely certain to LDL) remained detectable till greater than 4 days. Related observations had been made for MK-9 (LJ Schurgers, unpublished knowledge). It should be concluded, due to this fact, that the long-chain menaquinones stay accessible longer for take up by extrahepatic tissues and that extra fixed circulating ranges are generated as a result of the postprandial fluctuations are smaller than within the case of K1.
Vitamin Ok-insufficiency – “vitamin k blood coagulation”
Supplementation
Battle of curiosity and funding
The writer has not obtained any funding or advantages from trade or elsewhere to conduct this research.
“vitamin k blood coagulation”