|
|
| phylloquinone |
|
| CHEBI:18067 |
|
| A member of the class of phylloquinones that consists of 1,4-naphthoquinone having methyl and phytyl groups at positions 2 and 3 respectively. The parent of the class of phylloquinones. |
|
This entity has been manually annotated by the ChEBI Team.
|
|
|
CHEBI:11611, CHEBI:45148, CHEBI:8181, CHEBI:14833, CHEBI:26105
|
|
| ZINC000003831332 |
|
|
Molfile
XML
SDF
|
|
|
more structures >>
|
|
call loadScript javascripts\jsmol\core\package.js call loadScript javascripts\jsmol\core\core.z.js -- required by ClazzNode call loadScript javascripts\jsmol\J\awtjs2d\WebOutputChannel.js Jmol JavaScript applet jmolApplet0_object__994419449443222__ initializing getValue debug = null getValue logLevel = null getValue allowjavascript = null AppletRegistry.checkIn(jmolApplet0_object__994419449443222__) call loadScript javascripts\jsmol\core\corestate.z.js viewerOptions: { "name":"jmolApplet0_object","applet":true,"documentBase":"https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:11611","platform":"J.awtjs2d.Platform","fullName":"jmolApplet0_object__994419449443222__","display":"jmolApplet0_canvas2d","signedApplet":"true","appletReadyCallback":"Jmol._readyCallback","statusListener":"[J.appletjs.Jmol.MyStatusListener object]","codeBase":"https://www.ebi.ac.uk/chebi/javascripts/jsmol/","syncId":"994419449443222","bgcolor":"#000" } (C) 2012 Jmol Development Jmol Version: 13.2.7 $Date: 2013-10-01 11:35:15 -0500 (Tue, 01 Oct 2013) $ java.vendor: j2s java.version: 0.0 os.name: j2s Access: ALL memory: 0.0/0.0 processors available: 1 useCommandThread: false appletId:jmolApplet0_object (signed) starting HoverWatcher_1 getValue emulate = null defaults = "Jmol" getValue boxbgcolor = null getValue bgcolor = #000 backgroundColor = "#000" getValue ANIMFRAMECallback = null getValue APPLETREADYCallback = Jmol._readyCallback APPLETREADYCallback = "Jmol._readyCallback" getValue ATOMMOVEDCallback = null getValue CLICKCallback = null getValue ECHOCallback = null getValue ERRORCallback = null getValue EVALCallback = null getValue HOVERCallback = null getValue LOADSTRUCTCallback = null getValue MEASURECallback = null getValue MESSAGECallback = null getValue MINIMIZATIONCallback = null getValue PICKCallback = null getValue RESIZECallback = null getValue SCRIPTCallback = null getValue SYNCCallback = null getValue STRUCTUREMODIFIEDCallback = null getValue doTranslate = null language=en_US getValue popupMenu = null getValue script = null Jmol applet jmolApplet0_object__994419449443222__ ready call loadScript javascripts\jsmol\core\corescript.z.js call loadScript javascripts\jsmol\J\script\FileLoadThread.js starting QueueThread0_2 script 1 started starting HoverWatcher_3 starting HoverWatcher_4 The Resolver thinks Mol Marvin 02060822303D starting HoverWatcher_5 Time for openFile( Marvin 02060822303D 79 80 0 0 1 0 999 V2000 -5.9722 -6.3033 -0.5710 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1492 -5.7956 -1.5907 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7404 -5.3828 0.2002 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6403 -4.0193 -0.1022 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5700 -5.8756 1.2407 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0722 -7.6872 -0.2733 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8460 -3.5591 -1.1465 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6530 -7.2485 1.5176 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0811 -4.4360 -1.8682 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9032 -8.1570 0.7571 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2599 -3.2344 0.6113 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4883 -6.6036 -2.2365 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8289 -2.0987 -1.3845 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5745 -0.0746 -0.6130 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4983 0.4520 0.2257 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2390 0.8344 -1.5410 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1779 0.3095 -0.5621 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9370 0.8077 0.2023 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3892 0.6418 -0.5926 C 0 0 1 0 0 0 0 0 0 0 0 0 1.5276 1.3245 0.2176 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7018 -0.8385 -0.9823 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8814 1.2840 -0.5188 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0521 1.8790 0.2699 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4337 1.7871 -0.4542 C 0 0 1 0 0 0 0 0 0 0 0 0 6.5634 2.4680 0.3734 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8513 0.3343 -0.8298 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2824 3.9487 0.7238 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3374 4.6505 1.5989 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9605 6.1141 1.9875 C 0 0 2 0 0 0 0 0 0 0 0 0 8.1232 6.7537 2.7866 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6137 6.2690 2.7554 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8478 -1.3960 -0.5717 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1676 -3.9647 -2.9269 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1324 -5.2456 1.8190 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5410 -8.3839 -0.8015 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2579 -7.5846 2.2702 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9631 -9.1579 0.9551 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6703 -1.8597 -2.4361 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8076 -1.6483 -1.1969 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6629 1.4963 0.5032 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4106 -0.0857 1.1766 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3108 0.8592 -1.3438 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8743 1.8624 -1.4863 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0673 0.5091 -2.5692 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0548 -0.7522 -0.7829 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2363 0.8490 -1.5135 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1022 1.8667 0.4278 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8615 0.2793 1.1573 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2830 1.2038 -1.5272 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2754 2.3741 0.4077 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6308 0.8393 1.1934 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5746 -0.9290 -1.6266 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8601 -1.4463 -0.0893 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0793 -1.2940 -1.5854 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7903 1.7903 -1.4850 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1429 0.2447 -0.6762 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1181 1.4052 1.2545 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7431 2.9146 0.4186 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3427 2.3369 -1.3971 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4998 2.4275 -0.1896 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7144 1.9049 1.2994 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8436 0.3087 -1.2815 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1822 -0.1048 -1.5713 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8549 -0.3092 0.0528 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1139 4.5177 -0.1953 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3780 3.9762 1.3221 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2798 4.6392 1.0439 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4852 4.0577 2.5068 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8588 6.6842 1.0581 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0533 6.7122 2.2161 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2751 6.2287 3.7323 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9159 7.8031 3.0013 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4486 7.3028 3.0625 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5945 5.6370 3.6458 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7559 6.0068 2.1332 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3185 -1.9543 0.0655 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5537 -4.7261 -3.4111 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4550 -3.2429 -2.5211 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7263 -3.4964 -3.7390 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 12 2 0 0 0 0 3 1 4 0 0 0 0 3 4 1 0 0 0 0 4 11 2 0 0 0 0 3 5 4 0 0 0 0 1 6 4 0 0 0 0 4 7 1 0 0 0 0 7 13 1 0 0 0 0 5 8 4 0 0 0 0 7 9 2 0 0 0 0 2 9 1 0 0 0 0 9 33 1 0 0 0 0 6 10 4 0 0 0 0 8 10 4 0 0 0 0 13 32 1 0 0 0 0 32 14 2 0 0 0 0 14 15 1 0 0 0 0 14 16 1 0 0 0 0 15 17 1 0 0 0 0 17 18 1 0 0 0 0 18 19 1 0 0 0 0 19 20 1 0 0 0 0 19 21 1 0 0 0 0 20 22 1 0 0 0 0 22 23 1 0 0 0 0 23 24 1 0 0 0 0 24 25 1 0 0 0 0 24 26 1 0 0 0 0 25 27 1 0 0 0 0 27 28 1 0 0 0 0 28 29 1 0 0 0 0 29 30 1 0 0 0 0 29 31 1 0 0 0 0 5 34 1 0 0 0 0 6 35 1 0 0 0 0 8 36 1 0 0 0 0 10 37 1 0 0 0 0 13 38 1 0 0 0 0 13 39 1 0 0 0 0 15 40 1 0 0 0 0 15 41 1 0 0 0 0 16 42 1 0 0 0 0 16 43 1 0 0 0 0 16 44 1 0 0 0 0 17 45 1 0 0 0 0 17 46 1 0 0 0 0 18 47 1 0 0 0 0 18 48 1 0 0 0 0 19 49 1 0 0 0 0 20 50 1 0 0 0 0 20 51 1 0 0 0 0 21 52 1 0 0 0 0 21 53 1 0 0 0 0 21 54 1 0 0 0 0 22 55 1 0 0 0 0 22 56 1 0 0 0 0 23 57 1 0 0 0 0 23 58 1 0 0 0 0 24 59 1 0 0 0 0 25 60 1 0 0 0 0 25 61 1 0 0 0 0 26 62 1 0 0 0 0 26 63 1 0 0 0 0 26 64 1 0 0 0 0 27 65 1 0 0 0 0 27 66 1 0 0 0 0 28 67 1 0 0 0 0 28 68 1 0 0 0 0 29 69 1 0 0 0 0 30 70 1 0 0 0 0 30 71 1 0 0 0 0 30 72 1 0 0 0 0 31 73 1 0 0 0 0 31 74 1 0 0 0 0 31 75 1 0 0 0 0 32 76 1 0 0 0 0 33 77 1 0 0 0 0 33 78 1 0 0 0 0 33 79 1 0 0 0 0 M END): 24 ms reading 79 atoms ModelSet: haveSymmetry:false haveUnitcells:false haveFractionalCoord:false 1 model in this collection. Use getProperty "modelInfo" or getProperty "auxiliaryInfo" to inspect them. Default Van der Waals type for model set to Babel 79 atoms created ModelSet: not autobonding; use forceAutobond=true to force automatic bond creation Script completed Jmol script terminated
|
| Phytomenadione, also known as vitamin K1, phylloquinone, or phytonadione, is a vitamin found in food and used as a dietary supplement. It is on the World Health Organization's List of Essential Medicines.
It is used to treat certain bleeding disorders, including warfarin overdose, vitamin K deficiency, and obstructive jaundice. Use is typically recommended by mouth, intramuscular injection or injection under the skin. When given by injection benefits are seen within two hours. It is also recommended for preventing and treating vitamin K deficiency bleeding in infants. Many countries in the world choose intramuscular injections in newborn to keep them safe from vitamin K deficiency bleeding. It is considered a safe treatment and saves many children from death and severe neurologic deficit every year.
Side effects when given by injection may include pain at the site of injection. Severe allergic reactions may occur when it is injected into a vein or muscle, but this has mainly happened when large doses of a certain type of supplement containing castor oil were given intravenously. Use during pregnancy is considered safe, use is also likely okay during breastfeeding. It works by supplying a required component for making a number of blood clotting factors. Food sources include green vegetables, vegetable oil, and some fruit.
Phytomenadione was first isolated in 1939. In 1943 Edward Doisy and Henrik Dam were given a Nobel Prize for its discovery. |
|
Read full article at Wikipedia
|
InChI=1S/C31H46O2/c1- 22(2)12-9-13-23(3)14-10-15-24(4)16-11-17-25(5)20-21-27-26(6)30(32)28-18-7-8-19-29(28)31(27)33/h7-8,18-20,22-24H,9-17,21H2,1-6H3/b25-20+/t23-,24-/m1/s1 |
| MBWXNTAXLNYFJB-NKFFZRIASA-N |
| CC(C)CCC[C@@H](C)CCC[C@@H](C)CCC\C(C)=C\CC1=C(C)C(=O)C2=C(C=CC=C2)C1=O |
|
|
Homo sapiens
(NCBI:txid9606)
|
See:
DOI
|
|
Homo sapiens
(NCBI:txid9606)
|
Found in
blood plasma
(BTO:0000118).
See:
PubMed
|
|
human metabolite
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
plant metabolite
Any eukaryotic metabolite produced during a metabolic reaction in plants, the kingdom that include flowering plants, conifers and other gymnosperms.
cofactor
An organic molecule or ion (usually a metal ion) that is required by an enzyme for its activity. It may be attached either loosely (coenzyme) or tightly (prosthetic group).
mouse metabolite
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
(via vitamin K )
fat-soluble vitamin (role)
Any vitamin that dissolves in fats and are stored in body tissues. Unlike the water-soluble vitamins, they are stored in the body for long periods of time and generally pose a greater risk for toxicity when consumed in excess.
(via vitamin K )
|
|
View more via ChEBI Ontology
|
2-methyl-3-[(2E,7R,11R)-3,7,11,15-tetramethylhexadec-2-en-1-yl]naphthalene-1,4-dione
|
fitomenadiona
|
WHO MedNet
|
|
phytomenadione
|
WHO MedNet
|
phytoménadione
|
WHO MedNet
|
phytomenadionum
|
WHO MedNet
|
|
2-Methyl-3-(3,7,11,15-tetramethyl-2-hexadecenyl)-1,4-naphthalenedione
|
ChemIDplus
|
|
2-Methyl-3-[(2E)-3,7,11,15-tetramethyl-2-hexadecenyl]naphthoquinone
|
NIST Chemistry WebBook
|
2-Methyl-3-phytyl-1,4-naphthochinon
|
ChemIDplus
|
|
2-methyl-3-phytyl-1,4-naphthoquinone
|
KEGG COMPOUND
|
|
3-phytylmenadione
|
ChemIDplus
|
|
α-phylloquinone
|
NIST Chemistry WebBook
|
|
fitomenadione
|
ChemIDplus
|
|
Phyllochinon
|
ChemIDplus
|
|
Phyllochinonum
|
ChemIDplus
|
|
Phylloquinone
|
KEGG COMPOUND
|
|
PHYLLOQUINONE
|
PDBeChem
|
|
phylloquinone
|
UniProt
|
|
phytonadione
|
KEGG COMPOUND
|
|
Phytonadionum
|
ChemIDplus
|
|
Phytylmenadione
|
ChemIDplus
|
|
trans-Phylloquinone
|
NIST Chemistry WebBook
|
|
Vitamin K1
|
KEGG COMPOUND
|
|
vitamin K1
|
ChEBI
|
|
vitamin K1(20)
|
ChemIDplus
|
|
2568816
|
Reaxys Registry Number
|
Reaxys
|
|
84-80-0
|
CAS Registry Number
|
KEGG COMPOUND
|
|
84-80-0
|
CAS Registry Number
|
ChemIDplus
|
|
84-80-0
|
CAS Registry Number
|
NIST Chemistry WebBook
|
(2021)
Differential Impact of Dietary Vitamin K (phylloquinone) on Coagulation Factor Activities and Clotting Times in Warfarin-Treated Rats
Current developments in nutrition 5, 1310-1310 [PubMed Central:PMC8180628]
[show Abstract]
Abstract Objectives Investigate the impact of variable vitamin K (VK) intakes on the coagulation activities of four VK-dependent factors and clotting times, in warfarin-treated rats. Methods Male Wistar rats were randomly allocated to a AIN-93 based diet containing low (L: 80 mcg/kg/d), adequate (A: 750 mcg/kg/d) or enriched (E: 2000 mcg/kg/d) phylloquinone (K1) containing diet (n = 24/diet group). After one week, half the animals from each diet group were randomly allocated to receive 0.2 mg warfarin/kg/d through drinking water (W gp) or plain water (C gp), for 10 weeks. Coagulation activity (%) was assessed for factors II, VII, IX and X, and clotting times were based on prothrombin [PT (sec)] and activated thromboplastin times [APTT (sec)]. Measures were obtained at the end of the study and were conducted in the hospital clinical laboratory using standard procedures. Diet effects within C and W groups were investigated using one-way ANOVA and uncorrected Fisher post-hoc tests. Results Warfarin treatment resulted in significantly higher clotting times (PT and APTT) in all diet groups when compared to corresponding C groups (p < 0.05), the highest increase being observed in the L, followed by A and E groups, each diet being statistically different from each other (p < 0.01). Warfarin treatment also resulted in statistically significant decreases in activities of all coagulation factors although the impact of the diets varied according to factors: FVII and FX, between L and E groups only; FIX, between L and A, and L and E groups; FII, between all diet groups; (p < 0.05 in all cases). Conclusions Results from this study confirm the impact of dietary VK on coagulation factor activities and resulting clotting times, and suggest that for a given dose of W, this impact will depend on VK intake levels. Currently, individuals undergoing warfarin treatment are advised to aim for stable daily VK intakes. Results from this study provide data supporting this recommendation. Funding Sources This study was funded by CIHR and MHI Foundation. | EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP), Bampidis V, Azimonti G, Bastos ML, Christensen H, Dusemund B, Fašmon Durjava M, Kouba M, López-Alonso M, López Puente S, Marcon F, Mayo B, Pechová A, Petkova M, Ramos F, Ramos F, Sanz Y, Villa RE, Woutersen R, Groop J, Anguita M, Galobart J, Holczknecht O, Manini P, Pettenati E, Pizzo F, Tarrés-Call J (2021)
Safety and efficacy of an additive consisting of synthetic vitamin K1 (phytomenadione) for horses (JARAZ Enterprises GmbH & Co. KG).
EFSA journal. European Food Safety Authority 19, e06538 [PubMed:33968245]
[show Abstract]
Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of a feed additive consisting of vitamin K1 (phytomenadione) produced by chemical synthesis when used as a nutritional additive in complementary feed of horses at a maximum supplemental level of 14 mg vitamin K1/horse per day. The use of vitamin K1 is safe when used as a feed additive for horses under the proposed conditions of use. The use of vitamin K1 in nutrition of horses under the proposed conditions of use is considered safe for the consumer and the environment. No exposure of users by inhalation is expected. The Panel cannot conclude on the potential of the additive to be a skin and eye irritant. Vitamin K1 is considered a moderate dermal sensitiser. Vitamin K1 is an effective source of vitamin K in horse nutrition. The Panel recommends that the specifications of the additive refer to the substance-related impurities listed in the most updated monograph of the European Pharmacopoeia. | Sriwichai W, Collin M, Avallone S (2021)
Partial disintegration of vegetable cell wall during cooking improves vitamin K1 (phylloquinone) bioaccessibility in in vitro digestion.
International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition 91, 439-450 [PubMed:34134516]
[show Abstract]
Vegetables rich in vitamin K consumption could prevent bleeding and maintain bone status. The aims of the present work were to investigate i) the effect of household cooking (i.e., boiling for 5 min at 100 °C in distilled water and stir-frying for 3 min at 180 °C in hot canola oil) on phylloquinone bioaccessibility of five rich phylloquinone leafy vegetables, namely Water spinach (Ipomoea aquatic Forssk), Amaranth (Amaranthus blitum subsp. oleraceus L.), Chinese broccoli (Brassica alboglabra), Pak choi (Brassica rapa L.) and Drumstick (Moringa oleifera Lam.), and ii) the structural changes of these leaves before and after in vitro gastro-intestinal digestion. All the experiments were realized in triplicate for each vegetable. The amounts of phylloquinone in leafy vegetables were noticeable in almost all species and ranged from 94 to 182 μg/100 g DM. Their cell wall polysaccharide contents greatly varied from 4.3 to 8.4 g for 100 g. The content in bioaccessible phylloquinone was low in raw leaves (<25 μg/100 g DM) as well as its bioaccessibility (<15%). Leaf pectin content impaired phylloquinone bioaccessibility using principal component analysis. Boiling and stir-frying significantly improved the bioaccessibility of phylloquinone in leaves by a factor of three to twelve and two to seven respectively (p<0.05). These variations were associated with changes in leaf structure. Palisade and spongy cells appeared ruptured and disorganized after stir-frying. Given the estimated bioaccessibility of phylloquinones, the consumption of 500 g of cooked wet leaves per day would cover phylloquinone needs of an individual adult average body weight. | Gu X, Chen IG, Harding SA, Nyamdari B, Ortega MA, Clermont K, Westwood JH, Tsai CJ (2021)
Plasma membrane phylloquinone biosynthesis in nonphotosynthetic parasitic plants.
Plant physiology 185, 1443-1456 [PubMed:33793953]
[show Abstract]
Nonphotosynthetic holoparasites exploit flexible targeting of phylloquinone biosynthesis to facilitate plasma membrane redox signaling. Phylloquinone is a lipophilic naphthoquinone found predominantly in chloroplasts and best known for its function in photosystem I electron transport and disulfide bridge formation of photosystem II subunits. Phylloquinone has also been detected in plasma membrane (PM) preparations of heterotrophic tissues with potential transmembrane redox function, but the molecular basis for this noncanonical pathway is unknown. Here, we provide evidence of PM phylloquinone biosynthesis in a nonphotosynthetic holoparasite Phelipanche aegyptiaca. A nonphotosynthetic and nonplastidial role for phylloquinone is supported by transcription of phylloquinone biosynthetic genes during seed germination and haustorium development, by PM-localization of alternative terminal enzymes, and by detection of phylloquinone in germinated seeds. Comparative gene network analysis with photosynthetically competent parasites revealed a bias of P. aegyptiaca phylloquinone genes toward coexpression with oxidoreductases involved in PM electron transport. Genes encoding the PM phylloquinone pathway are also present in several photoautotrophic taxa of Asterids, suggesting an ancient origin of multifunctionality. Our findings suggest that nonphotosynthetic holoparasites exploit alternative targeting of phylloquinone for transmembrane redox signaling associated with parasitism. | Mi YN, Yan PP, Yu RH, Li QG, Wang CC, Hui MQ, Cao L, Cao YX (2020)
Determination of pharmacokinetic parameters of vitamin K1 in rats after an intravenous infusion.
Clinical and experimental pharmacology & physiology 47, 1439-1447 [PubMed:32222983]
[show Abstract]
Pharmacokinetic parameters of vitamin K1 have a large range of values in different literature. The aim of this study was to determine the pharmacokinetic parameters of vitamin K1 following post-constant speed intravenous infusion (PCSII) to provide rational pharmacokinetic parameters of vitamin K1 and compare these with results of noncompartmental analysis following intravenous injection (IV). After 15 hours intravenous infusion of vitamin K1 in rats, the logarithmic concentration-time curve of vitamin K1 was fit to a linear equation following PCSII (R2 = 0.9599 ± 0.0096). Then, half-time (T1/2 ), apparent volume of distribution (Vd ), and clearance rate (CL) were estimated successively. T1/2 of vitamin K1 was 4.07 ± 0.41 hour, CL was 89.47 ± 3.60 mL/h, and Vd was 525.38 ± 54.45 mL in rats following PCSII. There was no significant difference in pharmacokinetic parameters of vitamin K1 among different sampling times. For noncompartmental analysis, T1/2 and mean residence time (MRTINF ) for a sampling duration of 6h were shorter than those of 12 hours or 24 hours sampling duration following IV (P < .05, P < .01). In addition, T1/2 of vitamin K1 was obviously different from MRT-equated half-time (T1/2,MRT )(P < .05). Vd and CL of vitamin K1 following PCSII were larger than those following IV based on noncompartmental analysis (P < .01). The results demonstrated that drug distribution in the body was balanced and the Napierian logarithmic concentration-time curve of vitamin K1 fit to a linear equation following PCSII. Vitamin K1 has a long T1/2 and a relatively large Vd following PCSII. | Westerman K, Kelly JM, Ordovás JM, Booth SL, DeMeo DL (2020)
Epigenome-wide association study reveals a molecular signature of response to phylloquinone (vitamin K1) supplementation.
Epigenetics 15, 859-870 [PubMed:32090699]
[show Abstract]
Evidence suggests there are roles for vitamin K in various chronic disease outcomes, but population-level diet and supplement recommendations are difficult to determine due to high levels of variability in measures of status and response to intake compared to other nutrients. In this preliminary investigation, a blood-based epigenome-wide association study (EWAS) comparing responders and non-responders to phylloquinone (vitamin K1) supplementation (NCT00183001) was undertaken in order to better understand the molecular underpinnings of this observed variability. Responders (n = 24) and non-responders (n = 24) were identified in a prior 3-year phylloquinone supplementation trial based on their changes in plasma phylloquinone concentrations. Differential DNA methylation was identified in multiple regions with previously unknown relationships to phylloquinone absorption and metabolism, such as at the TMEM263 locus. A hypothesis-driven analysis of lipid-related genes highlighted a site in the NPC1L1 gene, supplementing existing evidence for its role in phylloquinone absorption. Furthermore, an EWAS for baseline plasma phylloquinone concentrations revealed a strong correlation between the epigenomic signatures of phylloquinone baseline status and response to supplementation. This work can guide future epigenomic research on vitamin K and contributes to the development of more personalized dietary recommendations for vitamin K. | Xiong Z, Liu Y, Chang T, Xu X, Huo S, Deng H, Liu T, Leng Y (2020)
Effect of vitamin K1 on survival of patients with chronic liver failure: A retrospective cohort study.
Medicine 99, e19619 [PubMed:32221088]
[show Abstract]
The effectiveness of vitamin K1 for the treatment of liver failure has been controversial, and no studies have investigated the effect of vitamin K1 on the risk of death and coagulation function in patients with chronic liver failure. This study aimed to explore the effect of vitamin K1 on death risk and international normalized ratio in patients with chronic liver failure.From December 2013 to August 2017, this retrospective cohort study screened patients hospitalized for chronic liver failure (n = 80) who received routine treatment. The patients were categorized into the vitamin K1 and control groups according to whether they had received intramuscular injection of vitamin K1 on the basis of conventional treatment. Baseline data were analyzed with χ test and independent sample t-test; the survival curve of 48 weeks was created with Kaplan-Meier estimator. Correlation between death event and vitamin K1, age, sex, albumin (ALB), total bilirubin (TBIL), and alkaline phosphatase (ALP) was determined with the Cox proportional risk regression model.Fifty-seven Chinese patients were finally included in the analysis. Patients treated with vitamin K1 had a lower risk of death (hazards ratio [HR] 0.37, P = 0.009) than the control group (P = 0.006). Men had a higher risk of death (HR 2.97, P = 0.005). Age, ALB, TBIL, and ALP had a certain correlation with risk of death. Vitamin K1 reduced the international normalized ratio levels [P < 0.01 (95% confidence interval 0.000-0.002)].Vitamin K1 may reduce the risk of death in patients with chronic liver failure. Male sex, age, ALB, TBIL, and ALP are potential risk factors for increased risk of death in these patients. Based on these findings, vitamin k1 can be used in patients with chronic liver failure. Prospective studies are still needed, however, to validate the role of vitamin K1 in the chronic liver failure. | Bates D, Edwards J, Langevin A, Abu-Ulba A, Yallou F, Wilson B, Ghosh S (2020)
Rebleeding in Variceal and Nonvariceal Gastrointestinal Bleeds in Cirrhotic Patients Using Vitamin K1: The LIVER-K Study.
The Canadian journal of hospital pharmacy 73, 19-26 [PubMed:32109957]
[show Abstract]
BackgroundGastroesophageal varices are the most common cause of upper gastrointestinal bleeding (UGIB) in patients with cirrhosis. Vitamin K1 is commonly administered to patients presenting with UGIB and elevated international normalized ratio, despite limited evidence to support this practice.ObjectivesThe primary objective was to describe the incidence of rebleeding within 30 days after vitamin K1 administration in patients with cirrhosis and UGIB. The secondary objective was to describe prescribing patterns for vitamin K1.MethodsThis retrospective, descriptive multicentre study involved patients with cirrhosis and UGIB who were admitted to any of the 4 adult acute care hospitals in Calgary, Alberta, from January 1, 2014, to December 31, 2016. Patients were divided into 2 groups: those who received vitamin K1 and those who did not.ResultsA total of 370 patients met the inclusion criteria, of whom 243 received vitamin K1 and 127 did not. Baseline characteristics were similar between the groups. Greater proportions of patients in the vitamin K1 group received transfusions of packed red blood cells, fresh frozen plasma, platelets, cryoprecipitate, or prothrombin concentrate during their admissions. There was no significant difference in the duration of octreotide and pantoprazole infusions. Among patients in the vitamin K1 group, there were more admissions to the intensive care unit and longer lengths of stay. More patients in the no vitamin K1 group had esophageal varices evident on endoscopy that required endoscopic treatment. Forty of the patients (16.5%) in the vitamin K1 group and 7 (5.5%) in the no vitamin K1 group had rebleeding within 30 days of the initial bleed. The median total vitamin K1 dose administered was 25 mg.ConclusionsThe study results suggest that vitamin K1 does not reduce the incidence of rebleeding within 30 days of the initial bleed in patients with cirrhosis and UGIB. | Boegh Andersen I, Brasen CL, Schmedes A, Brandslund I, Madsen JS (2020)
In Search of Normality for Vitamin K1: Establishing Age-Dependent Reference Intervals in the Danish Population.
The journal of applied laboratory medicine 5, 531-543 [PubMed:32445363]
[show Abstract]
BackgroundA growing body of evidence suggests that vitamin K has beneficial effects on human health, especially cardiovascular and bone health. Vitamin K1 (phylloquinone), the predominant form of vitamin K in blood, is regarded as an indicator of vitamin K status, but to our knowledge no reference intervals (RIs) have been established for vitamin K1.MethodsIn this population-based study, vitamin K1 was measured in serum from 3808 Caucasian individuals without diabetes from 26 to 78 years of age. The need for gender- and age-partitioned vitamin K1 reference intervals was evaluated using Lahti's method, and exclusion criteria were defined to obtain as healthy a study group as possible. The excluded subgroups were tested for differences in mean serum vitamin K1 levels. Serum vitamin K1 levels were quantified using an in-house newly developed, validated, and highly sensitive online SPE-LC-MS/MS method with a limit of quantitation of (LOQ) 0.05 nmol/L.ResultsThe reference interval for serum vitamin K1 was 0.22 to 3.95 nmol/L for individuals aged 26 to 44 years and 0.35 to 3.70 nmol/L for individuals aged 45 to 78. Similar age-specific reference intervals were established for vitamin K1-triglyceride ratio being 0.20 to 3.16 and 0.31 to 3.44, respectively. No significant difference was found between genders. Serum vitamin K1 was detectable in all serum samples. Individuals with known comorbidity were found to have significantly lower serum vitamin K1 compared to those without comorbidity. Current smokers had lower serum vitamin K1 compared to nonsmokers.ConclusionAge-dependent reference intervals were established for serum vitamin K1 and vitamin K1-triglyceride ratio in a well-defined, healthy Caucasian population. Lower serum vitamin K1 levels were found in individuals with known comorbidity, suggesting an association between serum vitamin K1 and disease status. Further studies are needed to determine an optimal serum vitamin K1 level. | Kelly J, Westerman K, Ordovas J, Booth S (2019)
Epigenome-wide Association Study of Plasma Phylloquinone Response to Phylloquinone Supplementation (OR31-04-19)
Current developments in nutrition 3, [PubMed Central:PMC6577341]
[show Abstract]
Abstract Objectives Genetics explains a small amount of the variability in the response of plasma phylloquinone to phylloquinone intake. Whether epigenetic modifications, which reflect interactions between the genome and environment, are related to the plasma phylloquinone response to supplementation has not been examined. The objective of this study was to conduct an epigenome-wide association study (EWAS) to identify genetic loci whose methylation levels associate with changes in circulating phylloquinone in response to phylloquinone supplementation. Methods We used data from a 3-year, randomized controlled, phylloquinone supplementation (500 ug/d) trial in healthy older adults. One hundred four white participants in the supplementation group who passed filters for adherence to the protocol (mean age = 68(5.0) years, 56% female) were classified as responders or non-responders according to their change in plasma phylloquinone. Of these, 24 participants with the smallest (non-responders) and 24 participants with the largest (responders) change in plasma phylloquinone were selected for DNA methylation analysis. DNA was isolated from baseline blood samples. Bisulfite-converted DNA for these 48 individuals was analyzed using the Illumina MethylationEPIC microarray platform at the Yale Center for Genome Analysis in New Haven, CT. The association of responder status with methylation beta-value at each site was examined using logistic regression adjusted for control-probe principal components. Results Forty (38%) of the 104 participants had changes in plasma phylloquinone that classified them as non-responders. A single CpG site (cg10918016 in NCOR2) was associated with plasma phylloquinone responder status at genome-wide Bonferroni level of significance (P < 6.4 × 10−8). In the presence of moderate genomic inflation (λ = 1.21), 5239 sites showed suggestive associations (Benjamini-Hochberg FDR < 0.2). Conclusions DNA methylation levels may contribute toward the inter-individual plasma phylloquinone response to supplementation. Larger studies in diverse populations are warranted to clarify the causal influence of methylation on the vitamin K status. Funding Sources Study supported by the USDA Agricultural Research Service under Cooperative Agreement No. 58-1950-7-707, NHLBI T32HL069772, and the Gerald Cassidy Student Research Award. *JMK and KW contributed equally to this research. Supporting Tables, Images and/or Graphs | Chatron N, Hammed A, Benoît E, Lattard V (2019)
Structural Insights into Phylloquinone (Vitamin K1), Menaquinone (MK4, MK7), and Menadione (Vitamin K3) Binding to VKORC1.
Nutrients 11, E67 [PubMed:30609653]
[show Abstract]
Vitamin K family molecules-phylloquinone (K1), menaquinone (K2), and menadione (K3)-act as γ-glutamyl carboxylase (GGCX)-exclusive cofactors in their hydroquinone state, activating proteins of main importance for blood coagulation in the liver and for arterial calcification prevention and energy metabolism in extrahepatic tissues. Once GGCX is activated, vitamin K is found in the epoxide state, which is then recycled to quinone and hydroquinone states by vitamin K epoxide reductase (VKORC1). Nevertheless, little information is available concerning vitamin K1, K2, or K3 tissue distribution and preferential interactions towards VKORC1. Here we present a molecular modeling study of vitamin K1, menaquinones 4, 7 (MK4, MK7), and K3 structural interactions with VKORC1. VKORC1 was shown to tightly bind vitamins K1 and MK4 in the epoxide and quinone states, but not in the hydroquinone state; five VKORC1 residues were identified as crucial for vitamin K stabilization, and two other ones were essential for hydrogen bond formation. However, vitamin MK7 revealed shaky binding towards VKORC1, induced by hydrophobic tail interactions with the membrane. Vitamin K3 exhibited the lowest affinity with VKORC1 because of the absence of a hydrophobic tail, preventing structural stabilization by the enzyme. Enzymatic activity towards vitamins K1, MK4, MK7, and K3 was also evaluated by in vitro assays, validating our in silico predictions: VKORC1 presented equivalent activities towards vitamins K1 and MK4, but much lower activity with respect to vitamin MK7, and no activity towards vitamin K3. Our results revealed VKORC1's ability to recycle both phylloquinone and some menaquinones, and also highlighted the importance of vitamin K's hydrophobic tail size and membrane interactions. | Basset GJ, Latimer S, Fatihi A, Soubeyrand E, Block A (2017)
Phylloquinone (Vitamin K1): Occurrence, Biosynthesis and Functions.
Mini reviews in medicinal chemistry 17, 1028-1038 [PubMed:27337968]
[show Abstract]
BackgroundPhylloquinone is a prenylated naphthoquinone that is synthesized exclusively by plants, green algae, and some species of cyanobacteria, where it serves as a vital electron carrier in photosystem I and as an electron acceptor for the formation of protein disulfide bonds.ObjectiveIn humans and other vertebrates, phylloquinone plays the role of a vitamin (vitamin K1) that is required for blood coagulation and bone and vascular metabolism. Phylloquinone from green leafy vegetables and vegetable oil represents the major dietary source of vitamin K for humans.MethodIn recent years, reverse genetics and biochemical approaches using the model plant Arabidopsis thaliana have shown that phylloquinone biosynthesis in plants involves paralogous and multifunctional enzymes, a compartmentation of the corresponding pathway in plastids and peroxisomes, and trafficking of some biosynthetic intermediates within plastids themselves. Furthermore, phylloquinone biosynthetic intermediates create crucial metabolic branch-points with other plastid-synthesized metabolites such as chlorophylls, tocopherols and salicylate.Results & conclusionThis review presents an update on recent studies of the central role of plastids in the biosynthesis of phylloquinone, in particular on the discovery of novel enzymatic steps that are likely paradigms for phylloquinone and menaquinone (vitamin K2)-synthesizing organisms alike. | Holmes MV, Hunt BJ, Shearer MJ (2012)
The role of dietary vitamin K in the management of oral vitamin K antagonists.
Blood reviews 26, 1-14 [PubMed:21914559]
[show Abstract]
Vitamin K antagonists (VKA) have been the mainstay of oral anticoagulant therapy for over 60years. In this review we critically assess the evidence for the importance of vitamin K nutrition during VKA therapy; the methodologies for measuring dietary intakes; the vitamin K intake data in patients on VKA and healthy people; and the experimental evidence for the influence of vitamin K intakes and biochemical measures of vitamin K status on VKA response. Several studies show that dietary intakes of phylloquinone (vitamin K1) are associated to the sensitivity and stability of anticoagulation during initiation and maintenance dosing with low habitual intakes associated with greater instability of the INR and risk of sub-therapeutic anticoagulation. Preliminary evidence suggests that the stability of anticoagulation therapy may be improved by daily vitamin K supplementation, but further studies are needed to find out whether this, or other dietary interventions, can improve anticoagulant control in routine clinical practice. | Terachi T, Inoue Y, Ashihara N, Kobayashi M, Ando K, Matsui T (2011)
Plasma vitamin K concentration in horses supplemented with several vitamin K homologs.
Journal of animal science 89, 1056-1061 [PubMed:21169510]
[show Abstract]
The effect of several vitamin K homologs on plasma vitamin K concentration was determined to assess their potential as a vitamin K supplement for adult horses. Sixteen Thoroughbred horses consisting of 8 mares and 8 geldings, aged 8.4 ± 3.6 yr and weighing 520.8 ± 36.1 kg, were allocated to 4 groups (n = 4). Each group was given phylloquinone, menaquinone-4, or menadione at 58 µmol/d, or no vitamin K supplement for 7 d. Plasma samples were collected before feeding, and 2, 4, and 8 h after feeding on d 7, and plasma concentrations of phylloquinone and menaquinone-4 were determined. Plasma phylloquinone concentration was greater in the phylloquinone group than in the other groups (P < 0.001). The phylloquinone concentration quadratically increased (P < 0.001) after feeding in the phylloquinone group but no changes in the plasma phylloquinone concentration were observed after feeding in the other groups. Plasma menaquinone-4 concentration was greater (P < 0.001) in the menadione group than the other groups, including the menaquinone-4 group. Menaquinone-4 concentration did not change (P = 0.192) after feeding in each group. Menaquinone-4 has been considered the most potent vitamin K homolog for bone metabolism; therefore, the present experiment indicates that menadione is a good source of vitamin K for bone health in horses because it is the only vitamin K homolog that increased the plasma concentrations of menaquinone-4. | Eugeni Piller L, Besagni C, Ksas B, Rumeau D, Bréhélin C, Glauser G, Kessler F, Havaux M (2011)
Chloroplast lipid droplet type II NAD(P)H quinone oxidoreductase is essential for prenylquinone metabolism and vitamin K1 accumulation.
Proceedings of the National Academy of Sciences of the United States of America 108, 14354-14359 [PubMed:21844348]
[show Abstract]
Lipid droplets are ubiquitous cellular structures in eukaryotes and are required for lipid metabolism. Little is currently known about plant lipid droplets other than oil bodies. Here, we define dual roles for chloroplast lipid droplets (plastoglobules) in energy and prenylquinone metabolism. The prenylquinones--plastoquinone, plastochromanol-8, phylloquinone (vitamin K(1)), and tocopherol (vitamin E)--are partly stored in plastoglobules. This work shows that NAD(P)H dehydrogenase C1 (NDC1) (At5g08740), a type II NAD(P)H quinone oxidoreductase, associates with plastoglobules. NDC1 reduces a plastoquinone analog in vitro and affects the overall redox state of the total plastoquinone pool in vivo by reducing the plastoquinone reservoir of plastoglobules. Finally, NDC1 is required for normal plastochromanol-8 accumulation and is essential for vitamin K(1) production. | Ahmed S, Kishikawa N, Ohyama K, Imazato T, Ueki Y, Kuroda N (2011)
Selective chemiluminescence method for monitoring of vitamin K homologues in rheumatoid arthritis patients.
Talanta 85, 230-236 [PubMed:21645693]
[show Abstract]
Vitamin K is a fat-soluble vitamin involved in blood coagulation and bone metabolism. The detection and monitoring of vitamin K homologues in rheumatoid arthritis (RA) patients is a challenging problem due to the smaller concentrations of vitamin K and the presence of several interfering medications. Therefore, this study aimed to develop a new highly sensitive and selective chemiluminescence (CL) method designated to quantify vitamin K homologues in plasma of RA patients including phylloquinone (PK, vitamin K(1)), menaquinone-4 (MK-4, vitamin K(2)) and menaquinone-7 (MK-7, vitamin K(2)). The method was based on the unique photochemical properties of vitamin K homologues that were exploited for selective luminol CL reaction. The correlation coefficients of 0.998 or more were obtained in the concentration ranges of 0.1-100 ng mL(-1) vitamin K homologues. The detection limits were 0.03-0.1 ng mL(-1) in human plasma for vitamin K homologues. The developed HPLC-CL system was successfully applied for selective determination of vitamin K homologues in plasma of RA patients. The developed method may provide a useful tool for monitoring vitamin K homologues in different clinical studies such as RA, osteoporosis and hepatocellular carcinoma in which vitamin K is intervented. | Yuan Y, Chung JD, Fu X, Johnson VE, Ranjan P, Booth SL, Harding SA, Tsai CJ (2009)
Alternative splicing and gene duplication differentially shaped the regulation of isochorismate synthase in Populus and Arabidopsis.
Proceedings of the National Academy of Sciences of the United States of America 106, 22020-22025 [PubMed:19996170]
[show Abstract]
Isochorismate synthase (ICS) converts chorismate to isochorismate for the biosynthesis of phylloquinone, an essential cofactor for photosynthetic electron transport. ICS is also required for salicylic acid (SA) synthesis during Arabidopsis defense. In several other species, including Populus, SA is derived primarily from the phenylpropanoid pathway. We therefore sought to investigate ICS regulation in Populus to learn the extent of ICS involvement in SA synthesis and defense. Arabidopsis harbors duplicated AtICS genes that differ in their exon-intron structure, basal expression, and stress inducibility. In contrast, we found a single ICS gene in Populus and six other sequenced plant genomes, pointing to the AtICS duplication as a lineage-specific event. The Populus ICS encodes a functional plastidic enzyme, and was not responsive to stresses that stimulated phenylpropanoid accumulation. Populus ICS underwent extensive alternative splicing that was rare for the duplicated AtICSs. Sequencing of 184 RT-PCR Populus clones revealed 37 alternative splice variants, with normal transcripts representing approximately 50% of the population. When expressed in Arabidopsis, Populus ICS again underwent alternative splicing, but did not produce normal transcripts to complement AtICS1 function. The splice-site sequences of Populus ICS are unusual, suggesting a causal link between junction sequence, alternative splicing, and ICS function. We propose that gene duplication and alternative splicing of ICS evolved independently in Arabidopsis and Populus in accordance with their distinct defense strategies. AtICS1 represents a divergent isoform for inducible SA synthesis during defense. Populus ICS primarily functions in phylloquinone biosynthesis, a process that can be sustained at low ICS transcript levels. | Niklas J, Epel B, Antonkine ML, Sinnecker S, Pandelia ME, Lubitz W (2009)
Electronic structure of the quinone radical anion A1*- of photosystem I investigated by advanced pulse EPR and ENDOR techniques.
The journal of physical chemistry. B 113, 10367-10379 [PubMed:19588895]
[show Abstract]
Vitamin K1 (VK1) is an important cofactor of the electron-transfer chain in photosystem I (PS I), referred to as A1. The special properties of this quinone result from its unique interaction(s) with the protein surrounding. In particular, a single H-bond to neutral A1 was identified previously in the X-ray crystal structure of PS I. During light-induced electron transfer in PS I, A1 is transiently reduced to the radical anion A1*-. In this work, we characterized the electron spin density distribution of A1*- with the aim of understanding the influence of the protein surrounding on it. We studied the light-induced spin-polarized radical pair P700*+A1*- and the photoaccumulated radical anion A1*-, using advanced pulse EPR, ENDOR, and TRIPLE techniques at Q-band (34 GHz). Exchange with fully deuterated quinone in the A1 binding site allowed differentiation between proton hyperfine couplings from the quinone and from the protein surrounding. In addition, DFT calculations on a model of the A1 site were performed and provided proton hyperfine couplings that were in close agreement with the ones determined experimentally. This combined approach allowed the assignment of proton hyperfine coupling tensors to molecular positions, thereby yielding a picture of the spin density distribution in A1*-. Comparison with VK1*- in organic solvents (Epel et al. J. Phys. Chem. B 2006, 110, 11549.) leads to the conclusion that the single H-bond present in both the radical pair P700*+A1*- and the photoaccumulated radical anion A1*- is, indeed, the crucial factor that governs the electronic structure of A1*-. | de Moerloose P, Boehlen F (2005)
[Haemostasis. A search for an ideal antithrombotics agent].
Revue medicale suisse 1, 35-38 [PubMed:15773196]
[show Abstract]
Heparins and vitamin K antagonist are the main antithrombotic agents used since several years. These two classes of drugs are very effective but not devoid of side effects and require either injections or regular laboratory controls. Therefore new agents have been developed. Two of these agents (fondaparinux and ximelagatran) are already available. Both are of non animal origin, do not induce thrombocytopenia and do not require laboratory controls. In recent studies fondaparinux has shown a better efficacy than low molecular weight heparin in major orthopedic interventions. Ximelagatran, which can be given orally, is now admitted also for short term use. It was hoped that it could replace vitamin K antagonists but increase of liver enzymes occurring after a few weeks is a major problem. Other new drugs are in advanced stage and will be also described. | Shimada H, Ohno R, Shibata M, Ikegami I, Onai K, Ohto MA, Takamiya K (2005)
Inactivation and deficiency of core proteins of photosystems I and II caused by genetical phylloquinone and plastoquinone deficiency but retained lamellar structure in a T-DNA mutant of Arabidopsis.
The Plant journal : for cell and molecular biology 41, 627-637 [PubMed:15686525]
[show Abstract]
Phylloquinone, a substituted 1,4-naphthoquinone with an 18-carbon-saturated phytyl tail, functions as a bound one-electron carrier cofactor at the A1 site of photosystem I (PSI). A Feldmann tag line mutant, no. 2755 (designated as abc4 hereafter), showed pale-green young leaves and white old leaves. The mutated nuclear gene encoded 1,4-dihydroxy-2-naphtoic acid phytyltransferase, an enzyme of phylloquinone biosynthesis, and high-performance liquid chromatography analysis revealed that the abc4 mutant contained no phylloquinone, and only about 3% plastoquinone. Photooxidation of P700 of PSI in the abc4 mutant was not observed, and reduced-versus-oxidized difference spectroscopy indicated that the abc4 mutant had no P700. The maximum quantum yield of photosystem II (PSII) in the abc4 mutant was much decreased, and the electron transfer from PSII to PSI in the abc4 mutant did not occur. For the pale-green leaves of the abc4 mutant plant, the ultrastructure of the chloroplasts was almost the same as that of the wild-type plant. However, the chloroplasts in the albino leaves of the mutant were smaller and had a lot of grana thylakoids and few stroma thylakoids. The amounts of PSI and PSII core subunits in the abc4 mutant were significantly decreased compared with those in the wild type. These results suggested that a deficiency of phylloquinone in PSI caused the abolishment of PSI and a partial defect of PSII due to a significant decrease of plastoquinone, but did not influence the ultrastructure of the chloroplasts in young leaves. | Wilkins K, DeKoven J, Assaad D (2000)
Cutaneous reactions associated with vitamin K1.
Journal of cutaneous medicine and surgery 4, 164-168 [PubMed:11003724]
[show Abstract]
BackgroundVitamin K1 (phytonadione) is a fat-soluble, naturally occurring vitamin used to treat certain coagulation disorders. A review of the adverse cutaneous reactions to Vitamin K1 is important because this diagnosis can be easily overlooked. This is due to their low incidence and because the presentation and morphology can vary considerably.ObjectiveThe objective of this article is to summarize the different morphologies, the natural history, and the treatment of the cutaneous reactions reported to Vitamin K1.MethodsA case of a patient who developed a localized eczematous plaque at the site of a vitamin K1 injection is outlined. A review of the English medical literature focused on the adverse cutaneous reactions associated with intramuscular or subcutaneous use of vitamin K1.ResultsOur patient developed a localized eczematous reaction to subcutaneous vitamin K1. The eruption developed within 7 days of her dose of vitamin K1. The eruption persisted for 18 months despite treatment with topical and intralesional steroids. There are three distinct types of cutaneous reactions to vitamin K1: localized eczematous, localized morphea-form, and, very rarely, diffuse maculopapular eruption. The eczematous type (32 cases) appears at the site of injection, and the median number of days between injection and appearance of the eruption is 13 days. The dose range required to initiate the reaction is broad (10 to 410 mg). Thirteen of 32 cases took more than 2 months to resolve. The morphea-form type (7 cases) is a localized morphea-form patch that appears at the site of injection. The average delay before presentation of morphea-form changes was 8.5 months (range: 5 weeks-1.5 years). The dose range is broad (30-2080 mg), and the prognosis for resolution very poor.ConclusionThe diagnosis of an adverse cutaneous reaction to vitamin K can be made if the possibility is considered. Many of these reactions are very slow to clear up and some may persist as a chronic sclerodermoid change. Managing these reactions may be frustrating for both the patient and the clinician. | Begley GS, Furie BC, Czerwiec E, Taylor KL, Furie GL, Bronstein L, Stenflo J, Furie B (2000)
A conserved motif within the vitamin K-dependent carboxylase gene is widely distributed across animal phyla.
The Journal of biological chemistry 275, 36245-36249 [PubMed:10893417]
[show Abstract]
The vitamin K-dependent gamma-glutamyl carboxylase catalyzes the posttranslational conversion of glutamic acid to gamma-carboxyglutamic acid, an amino acid critical to the function of the vitamin K-dependent blood coagulation proteins. Given the functional similarity of mammalian vitamin K-dependent carboxylases and the vitamin K-dependent carboxylase from Conus textile, a marine invertebrate, we hypothesized that structurally conserved regions would identify sequences critical to this common functionality. Furthermore, we examined the diversity of animal species that maintain vitamin K-dependent carboxylation to generate gamma-carboxyglutamic acid. We have cloned carboxylase homologs in full-length or partial form from the beluga whale (Delphinapterus leucas), toadfish (Opsanus tau), chicken (Gallus gallus), hagfish (Myxine glutinosa), horseshoe crab (Limulus polyphemus), and cone snail (Conus textile) to compare these structures to the known bovine, human, rat, and mouse cDNA sequences. Comparison of the predicted amino acid sequences identified a nearly perfectly conserved 38-amino acid residue region in all of these putative carboxylases. In addition, this amino acid motif is also present in the Drosophila genome and identified a Drosophila homolog of the gamma-carboxylase. Assay of hagfish liver demonstrated vitamin K-dependent carboxylase activity in this hemichordate. These results demonstrate the broad distribution of the vitamin K-dependent carboxylase gene, including a highly conserved motif that is likely critical for enzyme function. The vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid appears to be a highly conserved function in the animal kingdom. | Huang Y, Zhang C, Zhang X, Zhang Z (1999)
Chemiluminescence analysis of menadione sodium bisulfite and analgin in pharmaceutical preparations and biological fluids.
Journal of pharmaceutical and biomedical analysis 21, 817-825 [PubMed:10701947]
[show Abstract]
A novel chemiluminescence (CL) flow system for two sulfite-containing drugs, namely, menadione sodium bisulfite (MSB) and analgin is described. It is based on the weak chemiluminescence induced by the oxidation of sulfite group in drugs with dissolved oxygen in the presence of acidic Rh6G. Tween 80 surfactant micelles showed a strong enhancement effect on this weak chemiluminescence. For MSB analysis, online conversion of MSB in alkaline medium into sodium bisulfite was necessary, whereas analgin could be determined directly. The proposed method allowed the measurement of 0.05-50 microg/ml(-1) MSB and 0.05-10 microg/ml(-1) analgin. The limits of detection (3sigma) were 0.01 microg/ml(-1) MSB and 0.003 microg/ml(-1) analgin. The method was applied satisfactorily to pharmaceutical preparations as well as biological fluids. | Jakob E, Elmadfa I (1995)
Rapid HPLC assay for the assessment of vitamin K1, A, E and beta-carotene status in children (7-19 years).
International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition 65, 31-35 [PubMed:7657478]
[show Abstract]
The method presented allows the determination of plasma concentrations of the fat soluble vitamins K1, A, E and beta-carotene. After the extraction of the plasma, the only clean-up step required consisted of washing the hexane-layer with a methanol/water mixture. The RP-HPLC system contained a zinc-filled reduction post-column and after chromatographic separation the vitamin K was detected by fluorescence. Only 0.5-1 ml plasma was required for this procedure. 2',3'-Dihydrophylloquinone was added as an internal standard. For phylloquinone the limit of detection was estimated at 0.09 nmol/l (0.04 ng/ml). Investigating a plasma pool with a mean concentration of 0.75 nmol phylloquinone/l plasma, the all-over coefficient of variation was 5.6% for within-day (n = 11) and 7.1% from day to day (n = 8). The rate of recovery was found to be in the range of 92-104% (the same pool as for the precision test was used, and the added amounts were 0.13, 0.5, 2.0 ng phylloquinone). From an aliquot of hexane-extract, the vitamins A, E and beta-carotene were separated by RP-HPLC. The concentrations of vitamins A, E and beta-carotene were measured on the UV and visible detector respectively. Coefficients of variation for all vitamins were < 10%. In a group of 7 to 19 year-old healthy children (n = 298), the concentrations of vitamins A, E, K1 and beta-carotene ranged from 0.34-2.10 mumol/l, 12.0-80.8 mumol/l, 0.09-2.22 nmol/l and 0.23-3.92 mumol/l respectively, and the medians were 1.02 mumol/l, 21.3 mumol/l, 0.49 nmol/l and 0.56 mumol/l respectively. | Hirauchi K, Sakano T, Nagaoka T, Morimoto A (1988)
Simultaneous determination of vitamin K1, vitamin K1 2,3-epoxide and menaquinone-4 in human plasma by high-performance liquid chromatography with fluorimetric detection.
Journal of chromatography 430, 21-29 [PubMed:2851012]
[show Abstract]
A highly sensitive method for measuring endogenous vitamin K1, menaquinone-4 (which is one of the K2 vitamins) and vitamin K1 2,3-epoxide in human plasma was developed, based on high-performance liquid chromatography with coulometric reduction and fluorimetric detection, following extraction from plasma and purification on a Sep-Pak silica cartridge. The detection limits of vitamin K1, menaquinone-4 and vitamin K1 2,3-epoxide were 5, 5 and 8 pg per injection for the standard substances and 30, 30 and 50 pg/ml in human plasma, respectively. | Gover PA, Ingram GI, Cork MS, Holland L, Hopkins RP, Callaghan P, Barkhan P, Shearer MJ (1976)
Bleeding from self-administration of phenindione: a detailed case study.
British journal of haematology 33, 551-564 [PubMed:1009028]
[show Abstract]
A young woman presented with a 2 year history of a severe bleeding disorder and marked deficiencies in all four vitamin-K-dependent factors. Metabolic studies with tracer doses of tritium-labelled vitamin K1 suggested that the patient might be taking an oral anticoagulant; and subsequently her plasma was found to contain a substance identical to phenindione in its spectrophotometric and chromatographic properties. The half-disappearance times of factors II, IX, X were measured after the administration of a concentrate of these factors and were found to conform with published figures. The concentrate controlled the patient's excessive bruising and prolonged skin and gingival bleeding. It would therefore seem that factor VII may not be essential in reversal of the bleeding disorder induced by anticoagulant overdose. | Shearer MJ, Mallinson CN, Webster GR, Barkhan P (1970)
Absorption of tritiated vitamin K1 in patients with fat malabsorption.
Gut 11, 1063-1064 [PubMed:5511811] |
|
