Misplaced Pages

#448551

42-410: The number n of isoprenyl units in their side chain differs and ranges from 4 to 13, hence vitamin K 2 consists of various forms. It is indicated as a suffix (-n), e. g. MK-7 or MK-9. The most common in the human diet is the short-chain, water-soluble menatetrenone (MK-4), which is usually produced by tissue and/or bacterial conversion of vitamin K 1 , and is commonly found in animal products. It

84-407: A byproduct of the thermal cracking of petroleum naphtha or oil, as a side product in the production of ethylene . Where thermal cracking of oil is less common, isopentane can be dehydrogenated or isoprene can be synthesized from isobutylene and formaldehyde . Where cheap acetylene is produced from coal-derived calcium carbide , it may be combined with acetone to make 3-methylbutynol which

126-627: A factor required for coagulation, but the functions performed by this vitamin group were revealed to be much more complex. K vitamins play an essential role as cofactor for the enzyme γ-glutamyl carboxylase, which is involved in vitamin K-dependent carboxylation of the gla domain in "gla proteins" (i.e., in conversion of peptide-bound glutamic acid (glu) to γ-carboxy glutamic acid (Gla) in these proteins). Carboxylation of these vitamin K-dependent Gla-proteins , besides being essential for

168-443: A possibility of cis–trans isomerism due to the double bonds present. In M. phlei , the 3'-methyl- cis MK9 (II-H) form seems to be more biologically active than trans MK9 (II-H) . However, with human enzymes, the naturally abundant trans form is more efficient. One hydrogenated MK that sees relevant amounts of human consumption is MK-9(4H), found in cheese fermented by Propionibacterium freudenreichii . This variation has

210-420: A similar role as other quinones such as ubiquinone . Oxygen, heme, and menaquinones are needed for many species of lactic acid bacteria to conduct respiration. Variations in biosynthetic pathways mean that bacteria also produce analogues of vitamin K 2 . For example, MK9 (II-H) , which replaces the second geranylgeranyl unit with a saturated phytyl, is produced by Mycobacterium phlei . There also exists

252-503: A structural isomer that has similar, but not identical, properties. Gla domain Vitamin K-dependent carboxylation/gamma-carboxyglutamic ( GLA ) domain is a protein domain that contains post-translational modifications of many glutamate residues by vitamin K -dependent carboxylation to form γ-carboxyglutamate (Gla). Proteins with this domain are known informally as Gla proteins . The Gla residues are responsible for

294-422: Is about equivalent to methane emissions and accounts for around one-third of all hydrocarbons released into the atmosphere. In deciduous forests, isoprene makes up approximately 80% of hydrocarbon emissions. While their contribution is small compared to trees, microscopic and macroscopic algae also produce isoprene. Isoprene is made through the methyl-erythritol 4-phosphate pathway (MEP pathway, also called

336-444: Is absorbed along with dietary fat from the small intestine and transported by chylomicrons in the circulation. Most of vitamin K 1 is carried by triacylglycerol-rich lipoproteins (TRL) and rapidly cleared by the liver; only a small amount is released into the circulation and carried by LDL-C and HDL-C. MK-4 is carried by the same lipoproteins (TRL, LDL-C, and HDL-C) and cleared fast as well. The long-chain menaquinones are absorbed in

378-765: Is incorporated into and helps stabilize cell membranes in response to heat stress. Isoprene also confers resistance to reactive oxygen species. The amount of isoprene released from isoprene-emitting vegetation depends on leaf mass, leaf area, light (particularly photosynthetic photon flux density, or PPFD) and leaf temperature. Thus, during the night, little isoprene is emitted from tree leaves, whereas daytime emissions are expected to be substantial during hot and sunny days, up to 25 μg/(g dry-leaf-weight)/hour in many oak species. The isoprene skeleton can be found in naturally occurring compounds called terpenes and terpenoid (oxygenated terpenes), collectively called isoprenoids. These compounds do not arise from isoprene itself. Instead,

420-674: Is known that production of MK-4 from dietary plant vitamin K 1 can be accomplished by animal tissues alone, as it proceeds in germ-free rodents. However, at least one published study concluded that "MK-4 present in food does not contribute to the vitamin K status as measured by serum vitamin K levels. MK-7, however significantly increases serum MK-7 levels and therefore may be of particular importance for extrahepatic tissues." Long-chain menaquinones (longer than MK-4) include MK-7, MK-8 and MK-9 and are more predominant in fermented foods such as natto and cheonggukjang . Longer-chain menaquinones (MK-10 to MK-13) are produced by anaerobic bacteria in

462-699: Is noteworthy that most food assays measure only fully unsaturated menaquinones.) MK-4 is synthesized by animal tissues and is found in meat, eggs, and dairy products. Cheeses have been found to contain MK-8 at 10–20 μg per 100 g and MK-9 at 35–55 μg per 100 g. In one report, no substantial differences in MK-4 levels were observed between wild game, free-range animals, and factory farm animals. In addition to its animal origins, menaquinones are synthesized by bacteria during fermentation and so, as stated, are found in most fermented cheese and soybean products. As of 2001,

SECTION 10

#1733085977449

504-409: Is now known to be a circulating intermediate in the animal production of MK-4. Vitamin K 2 , the main storage form in animals, has several subtypes, which differ in isoprenoid chain length. These vitamin K 2 homologues are called menaquinones , and are characterized by the number of isoprenoid residues in their side chains. Menaquinones are abbreviated MK- n , where M stands for menaquinone,

546-618: Is often linked to undesired soft-tissue calcification in both children and adults. This process has been shown to be dependent upon the action of K vitamins. Vitamin K deficiency results in undercarboxylation of MGP. Also in humans on OAC treatment, two-fold more arterial calcification was found as compared to patients not receiving vitamin K antagonists. Among consequences of anticoagulant treatment: increased aortic wall stiffness, coronary insufficiency, ischemia, and even heart failure. Arterial calcification might also contribute to systolic hypertension and ventricular hypertrophy. Anticoagulant therapy

588-436: Is regulated both by substrate level and enzyme activity. Isoprene is the most abundant hydrocarbon measurable in the breath of humans. The estimated production rate of isoprene in the human body is 0.15 μmol /(kg·h), equivalent to approximately 17 mg/day for a person weighing 70 kg. Human breath isoprene originates from lipolytic cholesterol metabolism within the skeletal muscular peroxisomes and IDI2 gene acts as

630-548: Is then hydrogenated and dehydrated to isoprene. About 800,000 metric tons are produced annually. About 95% of isoprene production is used to produce cis-1,4-polyisoprene—a synthetic version of natural rubber . Natural rubber consists mainly of poly-cis-isoprene with a molecular mass of 100,000 to 1,000,000 g/mol. Typically natural rubber contains a few percent of other materials, such as proteins, fatty acids, resins, and inorganic materials. Some natural rubber sources, called gutta percha , are composed of trans-1,4-polyisoprene,

672-399: Is usually instituted to avoid life-threatening diseases, and high vitamin K intake interferes with anticoagulant effects. Patients on warfarin (Coumadin) or being treated with other vitamin K antagonists are therefore advised not to consume diets rich in K vitamins. Many bacteria synthesize menaquinones from chorismic acid . They use it as a part of the electron transport chain , playing

714-471: The K stands for vitamin K, and the n represents the number of isoprenoid side chain residues. For example, menaquinone-4 (abbreviated MK-4) has four isoprene residues in its side chain. Menaquinone-4 (also known as menatetrenone from its four isoprene residues) is the most common type of vitamin K 2 in animal products since MK-4 is normally synthesized from vitamin K 1 in certain animal tissues (arterial walls, pancreas, and testes) by replacement of

756-426: The colon , but they are not well absorbed at this level and have little physiological impact. When there are no isoprenyl side chain units, the remaining molecule is vitamin K 3 . This is usually made synthetically, and is used in animal feed . It was formerly given to premature infants , but due to inadvertent toxicity in the form of hemolytic anemia and jaundice , it is no longer used for this purpose. K 3

798-531: The US Institute of Medicine , on reviewing existing evidence, have decided there is insufficient evidence to publish a dietary reference value for vitamin K or for K 2 . They have, however, published an Adequate Intake (AI) for vitamin K, but no value specifically for K 2 . Parts of the scientific literature, dating back to 1998, suggest that the AI values are based only on the hepatic requirements (i.e. related to

840-446: The carboxylase. The 3D structures of several Gla domains have been solved. Calcium ions induce conformational changes in the Gla domain and are necessary for the Gla domain to fold properly. A common structural feature of functional Gla domains is the clustering of N-terminal hydrophobic residues into a hydrophobic patch that mediates interaction with the cell surface membrane. At present,

882-400: The cell membrane monolayer of many Archaea , filling the space between the diglycerol tetraether head groups. This is thought to add structural resistance to harsh environments in which many Archaea are found. Similarly, natural rubber is composed of linear polyisoprene chains of very high molecular weight and other natural molecules. Isoprene is most readily available industrially as

SECTION 20

#1733085977449

924-461: The colon by Escherichia coli bacteria . However, these menaquinones synthesized by bacteria in the gut appear to contribute minimally to overall vitamin K status. MK-4 and MK-7 are both found in the United States in dietary supplements for bone health. All K vitamins are similar in structure: they share a " quinone " ring, but differ in the length and degree of saturation of the carbon tail and

966-575: The compound in 1860 after obtaining it from the pyrolysis of natural rubber. He correctly deduced the mass shares of carbon and hydrogen (but due to modern atomic weight of carbon not yet adopted at the Karlsruhe Congress arrived at an incorrect formula C 10 H 8 ). He didn't specify the reasons for the name, but it's hypothesized that it came from "propylene" with which isoprene shares some physical and chemical properties. The first one to observe recombination of isoprene into rubber-like substance

1008-641: The following human Gla-containing proteins (Gla 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 , periostin (a factor necessary for migration and adhesion of epithelial cells), plus two proline-rich Gla-proteins (PRGPs) and two transmembrane Gla proteins (TMGPs),

1050-512: The function of the protein, is also an important vitamin recovery mechanism since it serves as a recycling pathway to recover vitamin K from its epoxide metabolite (KO) for reuse in carboxylation. Several human Gla-containing proteins synthesized in several different types of tissue have been discovered: Vitamin may have a protective effect on bone mineral density and reduced risk of hip, vertebral and non-vertebral fractures. These effects appear to be accentuated when combined with vitamin D and in

1092-510: The high-affinity binding of calcium ions. The GLA domain binds calcium ions by chelating them between two carboxylic acid residues. These residues are part of a region that starts at the N-terminal extremity of the mature form of Gla proteins, and that ends with a conserved aromatic residue. This results in a conserved Gla-x(3)-Gla-x-Cys motif that is found in the middle of the domain, and which seems to be important for substrate recognition by

1134-626: The hypothesis that isoprene may protect plants against heat stress (thermotolerance hypothesis, see below). Emission of isoprene is also observed in some bacteria and this is thought to come from non-enzymatic degradations from DMAPP. Global emission of isoprene by plants is estimated at 350 million tons per year. Isoprene emission in plants is controlled both by the availability of the substrate (DMAPP) and by enzyme (isoprene synthase) activity. In particular, light, CO 2 and O 2 dependencies of isoprene emission are controlled by substrate availability, whereas temperature dependency of isoprene emission

1176-584: The intake of either K 1 or K 2 ". Animal models involving rats, if generalisable to humans, show that MK-7 is well tolerated. Apart from animal livers, the richest dietary source of menaquinones are fermented foods (from bacteria, not molds or yeasts); sources include cheeses consumed in Western diets (e.g., containing MK-9, MK-10, and MK-11) and fermented soybean products (e.g., in traditional nattō consumed in Japan, containing MK-7 and MK-8). (Here and following it

1218-625: The intense smell and strong taste of nattō appear to make this soya food a less attractive source of K 2 for Western tastes. Supplement companies sell nattō extract reportedly standardized with regard to K 2 content, in capsule form. Notes: Recent studies found a clear association between long-term oral (or intravenous) anticoagulant treatment (OAC) and reduced bone quality due to reduction of active osteocalcin . OAC might lead to an increased incidence of fractures, reduced bone mineral density or content, osteopenia , and increased serum levels of undercarboxylated osteocalcin. Furthermore, OAC

1260-470: The liver). This hypothesis is supported by the fact that the majority of the Western population exhibits a substantial fraction of undercarboxylated extra-hepatic proteins. Thus, complete activation of coagulation factors is satisfied, but there does not seem to be enough vitamin K 2 for the carboxylation of osteocalcin in bone and MGP in the vascular system. There is no known toxicity associated with high doses of menaquinones (vitamin K 2 ). Unlike

1302-485: The non- mevalonate pathway ) in the chloroplasts of plants. One of the two end-products of MEP pathway, dimethylallyl pyrophosphate (DMAPP), is cleaved by the enzyme isoprene synthase to form isoprene and diphosphate. Therefore, inhibitors that block the MEP pathway, such as fosmidomycin , also block isoprene formation. Isoprene emission increases dramatically with temperature and maximizes at around 40 °C. This has led to

Vitamin K2 - Misplaced Pages Continue

1344-429: The number of repeating isoprene units in the "side chain". The number of repeating units is indicated in the name of the particular menaquinone (e.g., MK-4 means that four isoprene units are repeated in the carbon tail). The chain length influences lipid solubility and thus transport to different target tissues. The mechanism of action of vitamin K 2 is similar to vitamin K 1 . K vitamins were first recognized as

1386-537: The other fat-soluble vitamins, vitamin K is not stored in any significant quantity in the liver . All data available as of 2017 demonstrate that vitamin K has no adverse effects in healthy subjects. The recommendations for the daily intake of vitamin K, as issued recently by the US Institute of Medicine, also acknowledge the wide safety margin of vitamin K: "a search of the literature revealed no evidence of toxicity associated with

1428-412: The phytyl tail with an unsaturated geranylgeranyl tail containing four isoprene units, thus yielding menaquinone-4 which is water soluble in nature. This homolog of vitamin K 2 may have enzyme functions distinct from those of vitamin K 1 . MK-7 and other long-chain menaquinones are different from MK-4 in that they are not produced by human tissue. MK-7 may be converted from phylloquinone (K 1 ) in

1470-409: The precursor to isoprene units in biological systems is dimethylallyl pyrophosphate (DMAPP) and its isomer isopentenyl pyrophosphate (IPP). The plural 'isoprenes' is sometimes used to refer to terpenes in general. Examples of isoprenoids include carotene , phytol , retinol ( vitamin A ), tocopherol ( vitamin E ), dolichols , and squalene . Heme A has an isoprenoid tail, and lanosterol ,

1512-601: The production determinant. Due to the absence of IDI2 gene, animals such as pigs and bottle-nose dolphins do not exhale isoprene. Isoprene is common in low concentrations in many foods. Many species of soil and marine bacteria, such as Actinomycetota , are capable of degrading isoprene and using it as a fuel source. Isoprene emission appears to be a mechanism that trees use to combat abiotic stresses . In particular, isoprene has been shown to protect against moderate heat stress (around 40 °C). It may also protect plants against large fluctuations in leaf temperature. Isoprene

1554-1058: The richest known source of natural K 2 was nattō fermented using the nattō strain of Bacillus subtilis , which is reportedly a good source of long-chain MK-7. In nattō, MK-4 is absent as a form of vitamin K, and in cheeses it is present among the vitamins K only in low proportions. Still it is unknown whether B. subtilis will produce K 2 using other legumes (e.g., chickpeas , or lentils ) or even B. subtilis fermented oatmeal . According to Rebecca Rocchi et al., 2024, creating natto by using Bacillus subtilis to ferment boiled red lentils , chickpeas , or green peas produced greater amounts of MK-7 than creating natto by using Bacillus subtilis to ferment boiled soybeans , lupins , or brown beans . Food frequency questionnaire-derived estimates of relative intakes of vitamins K in one northern European country suggest that for that population, about 90% of total vitamin K intakes are provided by K 1 , about 7.5% by MK-5 through MK-9 and about 2.5% by MK-4;

1596-498: The same way as vitamin K 1 and MK-4 but are efficiently redistributed by the liver in predominantly LDL-C (VLDL-C). Since LDL-C has a long half-life in the circulation, these menaquinones can circulate for extended times resulting in higher bioavailability for extra-hepatic tissues as compared to vitamin K 1 and MK-4. Accumulation of vitamin K in extra-hepatic tissues has direct relevance to vitamin K functions not related to hemostasis. The European Food Safety Authority ( EU ) and

1638-399: The second and third units replaced with phytyl. Isoprenyl Isoprene , or 2-methyl-1,3-butadiene , is a common volatile organic compound with the formula CH 2 =C(CH 3 )−CH=CH 2 . In its pure form it is a colorless volatile liquid. It is produced by many plants and animals (including humans) and its polymers are the main component of natural rubber . C. G. Williams named

1680-427: The setting of osteoporosis . Research suggests that vitamin K 2 (Menaquinone 7, MK-7]) may reduce the rate and severity of night time leg cramps. With regard to utilisation, reports suggest that vitamin K 2 is preferred by the extrahepatic tissues (bone, cartilage, vasculature), which may be produced as MK-4 by the animal from K 1 , or it may be of bacterial origin (from MK-7, MK-9, and other MKs). Vitamin K

1722-474: The sterol precursor in animals, is derived from squalene and hence from isoprene. The functional isoprene units in biological systems are dimethylallyl pyrophosphate (DMAPP) and its isomer isopentenyl pyrophosphate (IPP), which are used in the biosynthesis of naturally occurring isoprenoids such as carotenoids , quinones , lanosterol derivatives (e.g. steroids) and the prenyl chains of certain compounds (e.g. phytol chain of chlorophyll). Isoprenes are used in

Vitamin K2 - Misplaced Pages Continue

1764-431: Was Gustave Bouchardat  [ de ] in 1879, and William A. Tilden identified its structure five years later. Isoprene is produced and emitted by many species of trees (major producers are oaks , poplars , eucalyptus , and some legumes). Yearly production of isoprene emissions by vegetation is around 600 million metric tons , half from tropical broadleaf trees and the remainder primarily from shrubs . This

#448551