Article by hi joiney

Chemical structure All members of the vitamin K group of vitamins share a methylated naphthoquinone ring structure and vary in the aliphatic side chain attached at the 3 position see figure 1 Phylloquinone also known as vitamin K1 invariably contains in its side chain four isoprenoid residues one of which is unsaturated Menaquinones have side chains composed of a variable number of unsaturated isoprenoid residues generally they are designated as MK n where n specifies the number of isoprenoids It is generally accepted that the naphthoquinone is the functional group so that the mechanism of action is similar for all K vitamins Substantial differences may be expected however with respect to intestinal absorption transport tissue distribution and bio availability These differences are caused by the different lipophilicity of the various side chains and by the different food matrices in which they occur Physiology Vitamin K is involved in the carboxylation of certain glutamate residues in proteins to form gamma carboxyglutamate residues abbreviated Gla residues The modified residues are often but not always situated within specific protein domains called Gla domains Gla residues are usually involved in binding calcium The Gla residues are essential for the biological activity of all known Gla proteins At this time update 14 human proteins with Gla domains have been discovered and they play key roles in the regulation of three physiological processes Blood coagulation prothrombin factor II factors VII IX X protein C protein S and protein Z Bone metabolism osteocalcin also called bone Gla protein BGP and matrix gla protein MGP Vascular biology Recommended amounts The U S Dietary Reference Intake DRI for an Adequate Intake AI of vitamin K for a 25 year old male is 120 micrograms day The Adequate Intake AI of this phytonutrient for adult women is 90 micrograms day for infants is 1020 micrograms day for children and adolescents 15100 micrograms day In 2002 it was found that to get maximum carboxylation of osteocalcin one may have to take up to 1000 g of vitamin K1 Like other liposoluble vitamins A D E vitamin K is stored in the fat tissue of the human body Toxicity Although allergic reaction from supplementation is possible there is no known toxicity associated with high doses of the phylloquinone vitamin K1 or menaquinone vitamin K2 forms of vitamin K and therefore no Tolerable Upper Intake Level UL has been set However a synthetic form of vitamin K vitamin K3 menadione is demonstrably toxic In fact the FDA has banned this synthetic form of the vitamin from over the counter supplements because large doses have been shown to cause allergic reactions hemolytic anemia and cytotoxicity in liver cells Drug Interactions Phylloquinone K1 or menaquinone K2 are capable of blocking the blood thinning action of anticoagulants like warfarin which work by interfering with the action of vitamin K They also reverse the tendency of these drugs to cause arterial calcification in the long term Sources Vitamin K1 is found chiefly in leafy green vegetables such as spinach swiss chard and Brassica e g cabbage kale cauliflower broccoli and brussels sprouts some fruits such as avocado and kiwifruit are also high in vitamin K By way of reference two tablespoons of parsley contain 153 of the recommended daily amount of vitamin K Some vegetable oils notably soybean contain vitamin K but at levels that would require relatively large caloric consumption to meet the USDA recommended levels It is believed that phylloquinone s tight binding to the thylakoid membranes in the chloroplasts is the reason behind the poor bioavailability of vitamin K in green plants For example cooked spinach has a 4 percent bioavailability of phylloquinone However when one adds butter to the spinach the bioavailability increases to 13 percent due to the increased solubility of vitamin K in fat Menaquinone 4 and menaquinone 7 vitamin K2 are found in meat eggs dairy and natto MK 4 is synthesized by animal tissues the rest mainly MK 7 are synthesized by bacteria during fermentation In natto 0 of vitamin K is from MK 4 and in cheese 27 Gut bacteria produce significant amounts of usable vitamin K In haemorrhagic disease of the newborn the gut has not yet been colonized with bacteria and to prevent this disease vitamin K shots are given to babies born in the US Similarly persons on large doses of antibiotics are at risk for developing vitamin K deficiency because of a lack of normal flora Deficiency Main article Vitamin K deficiency Average diets are usually not lacking in vitamin K and primary vitamin K deficiency is rare in healthy adults As previously mentioned newborn infants are at an increased risk of deficiency Other populations with an increased prevalence of vitamin K deficiency include individuals who suffer from liver damage or disease e g alcoholics people with cystic fibrosis inflammatory bowel diseases or those who have recently had abdominal surgeries Groups which may suffer from secondary vitamin K deficiency include bulimics those on stringent diets and those taking anticoagulants Other drugs which have been associated with vitamin K deficiency include salicylates barbiturates and cefamandole although the mechanism is still unknown There is no difference between the sexes as both males and females are affected equally Symptoms of deficiency include heavy menstrual bleeding in women anemia bruising and bleeding of the gums or nose Osteoporosis and coronary heart disease are strongly associated with lower levels of K2 menaquinone Menaquinone is not inhibited by salicylates as happens with K1 so menaquinone supplementation can alleviate the chronic vitamin K deficiency caused by long term aspirin use citation needed Biochemistry Discovery In 1929 Danish scientist Henrik Dam investigated the role of cholesterol by feeding chickens a cholesterol depleted diet After several weeks the animals developed hemorrhages and started bleeding These defects could not be restored by adding purified cholesterol to the diet It appeared thatogether with the cholesterol second compound had been extracted from the food and this compound was called the coagulation vitamin The new vitamin received the letter K because the initial discoveries were reported in a German journal in which it was designated as Koagulationsvitamin Edward Adelbert Doisy of Saint Louis University did much of the research that led to the discovery of the structure and chemical nature of vitamin K Dam and Doisy shared the 1943 Nobel Prize for medicine for their work on vitamin K Several laboratories synthesized the compound in 1939 For several decades the vitamin K deficient chick model was the only method of quantifying vitamin K in various foods the chicks were made vitamin K deficient and subsequently fed with known amounts of vitamin K containing food The extent to which blood coagulation was restored by the diet was taken as a measure for its vitamin K content Three groups of physicians independently found this Biochemical Institute University of Copenhagen Dam and Johannes Glavind University of Iowa Department of Pathology Emory Warner Kenneth Brinkhous and Harry Pratt Smith and the Mayo Clinic Hugh Butt Albert Snell and Arnold Osterberg The first published report of successful treatment with vitamin K of life threatening hemorrhage in a jaundiced patient with prothrombin deficiency was made in 1938 by Smith Warner and Brinkhous Function in the cell The precise function of vitamin K was not discovered until 1974 when three laboratories Stenflo et al Nelsestuen et al and Magnusson et al isolated the vitamin K dependent coagulation factor prothrombin Factor II from cows that received a high dose of a vitamin K antagonist warfarin It was shown that while warfarin treated cows had a form of prothrombin that contained 10 glutamate amino acid residues near the amino terminus of this protein the normal untreated cows contained 10 unusual residues which were chemically identified as gamma carboxyglutamate or Gla The extra carboxyl group in Gla made clear that vitamin K plays a role in a carboxylation reaction during which Glu is converted into Gla The biochemistry of how vitamin K is used to convert Glu to Gla has been elucidated over the past thirty years in academic laboratories throughout the world Within the cell vitamin K undergoes electron reduction to a reduced form of vitamin K called vitamin K hydroquinone by the enzyme vitamin K epoxide reductase or VKOR Another enzyme then oxidizes vitamin K hydroquinone to allow carboxylation of Glu to Gla this enzyme is called the gamma glutamyl carboxylase or the vitamin K dependent carboxylase The carboxylation reaction will only proceed if the carboxylase enzyme is able to oxidize vitamin K hydroquinone to vitamin K epoxide at the same time the carboxylation and epoxidation reactions are said to be coupled reactions vitamin K epoxide is then re converted to vitamin K by vitamin K epoxide reductase These two enzymes comprise the so called vitamin K cycle One of the reasons humans are rarely deficient in vitamin K is that vitamin K is continually recycled in our cells Warfarin and other coumarin drugs block the action of the vitamin K epoxide reductase This results in decreased concentrations of vitamin K and vitamin K hydroquinone in the tissues such that the carboxylation reaction catalyzed by the glutamyl carboxylase is inefficient This results in the production of clotting factors with inadequate Gla Without Gla on the amino termini of these factors they no longer bind stably to the blood vessel endothelium and cannot activate clotting to allow formation of a clot during tissue injury As it is impossible to predict what dose of warfarin will give the desired degree of suppression of the clotting warfarin treatment must be carefully monitored to avoid over dosing See the warfarin article Methods of assessment Prothrombin time test Measures the time required for blood to clot Blood sample mixed with citric acid and put in a fibrometer Delayed clot formation indicates a deficiency Unfortunately insensitive to mild deficiency as the values do not change until the concentration of prothrombin in the blood has declined by at least 50 percent Plasma Phylloquinone Was found to be positively correlated with phylloquinone intake in elderly British women but not men However an article by Schurges et al reported no correlation between FFQ and plasma phylloquinone Urinary carboxyglutamic acid Urinary Gla responds to changes in dietary vitamin K intake Several days are required before any change can be observed In a study by Booth et al increases of phylloquinone intakes from 100 g to between 377417 g for 5 days did not induce a significant change Response may be age specific Gla proteins At present the following human Gla containing proteins have been characterized to the level of primary structure the blood coagulation factors II prothrombin VII IX and X the anticoagulant proteins C and S and the Factor X targeting protein Z The bone Gla protein osteocalcin the calcification inhibiting matrix gla protein MGP the cell growth regulating growth arrest specific gene 6 protein Gas6 and the four transmembrane Gla proteins TMGPs the function of which is at present unknown Gas6 can function as a growth factor that activates the Axl receptor tyrosine kinase and stimulates cell proliferation or prevents apoptosis in some cells In all cases in which their function was known the presence of the Gla residues in these proteins turned out to be essential for functional activity Gla proteins are known to occur in a wide variety of vertebrates mammals birds reptiles and fish The venom of a number of Australian snakes acts by activating the human blood clotting system Remarkably in some cases activation is accomplished by snake Gla containing enzymes that bind to the endothelium of human blood vessels and catalyze the conversion of procoagulant clotting factors into activated ones leading to unwanted and potentially deadly clotting Another interesting class of invertebrate Gla containing proteins is synthesized by the fish hunting snail Conus geographus These snails produce a venom containing hundreds of neuro active peptides or conotoxins which is sufficiently toxic to kill an adult human Several of the conotoxins contain 25 Gla residues Function in bacteria Many bacteria such as Escherichia coli found in the large intestine can synthesize vitamin K2 menaquinone but not vitamin K1 phylloquinone In these bacteria menaquinone will transfer two electrons between two different small molecules in a process called anaerobic respiration For example a small molecule with an excess of electrons also called an electron donor such as lactate formate or NADH with the help of an enzyme will pass two electrons to a menaquinone The menaquinone with the help of another enzyme will in turn transfer these 2 electrons to a suitable oxidant such fumarate or nitrate also called an electron acceptor Adding two electrons to fumarate or nitrate will convert the molecule to succinate or nitrite water respectively Some of these reactions generate a cellular energy source ATP in a manner similar to eukaryotic cell aerobic respiration except that the final electron acceptor is not molecular oxygen but say fumarate or nitrate In aerobic respiration the final oxidant is molecular oxygen O2 which accepts four electrons from an electron donor such as NADH to be converted to water Escherichia coli can carry out aerobic respiration and menaquninone mediated anaerobic respiration Vitamin K injection in newborns The blood clotting factors of newborn babies are roughly 30 to 60 percent that of adult values this may be due to the reduced synthesis of precursor proteins and the sterility of their guts Human milk contains between 1 and 4 micrograms litre of vitamin K1 while formula derived milk can contain up to 100 micrograms litre in supplemented

2nd track on Incubus’ second album, SCIENCE