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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__816196783868818__ initializing getValue debug = null getValue logLevel = null getValue allowjavascript = null AppletRegistry.checkIn(jmolApplet0_object__816196783868818__) 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:6264","platform":"J.awtjs2d.Platform","fullName":"jmolApplet0_object__816196783868818__","display":"jmolApplet0_canvas2d","signedApplet":"true","appletReadyCallback":"Jmol._readyCallback","statusListener":"[J.appletjs.Jmol.MyStatusListener object]","codeBase":"https://www.ebi.ac.uk/chebi/javascripts/jsmol/","syncId":"816196783868818","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__816196783868818__ 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 07280814463D starting HoverWatcher_5 Time for openFile( Marvin 07280814463D 25 24 0 0 0 0 999 V2000 -0.1131 2.8105 0.1980 N 0 0 0 0 0 0 0 0 0 0 0 0 0.7363 1.6461 0.4840 C 0 0 2 0 0 0 0 0 0 0 0 0 2.1285 1.9012 -0.0320 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3152 2.7450 -0.8760 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1556 0.4101 -0.2060 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2071 0.0782 0.4070 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7886 -1.1584 -0.2830 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1500 -1.4906 0.3290 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7083 -2.6782 -0.3320 N 0 3 0 0 0 0 0 0 0 0 0 0 3.1625 1.1898 0.4460 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1172 2.9267 -0.8040 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0519 2.5570 0.4640 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7727 1.4791 1.5600 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0563 1.3538 0.1150 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0366 0.6098 -1.2700 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8310 -0.4344 -0.0680 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0875 -0.1223 1.4710 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8833 0.9220 0.2690 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9076 -0.9587 -1.3480 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1124 -2.0023 -0.1450 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0317 -1.6908 1.3940 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8262 -0.6467 0.1920 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8184 -2.4919 -1.3180 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0827 -3.4588 -0.2050 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6068 -2.8973 0.0710 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 1 11 1 0 0 0 0 1 12 1 0 0 0 0 2 3 1 0 0 0 0 2 5 1 0 0 0 0 2 13 1 0 0 0 0 3 4 2 0 0 0 0 3 10 1 0 0 0 0 5 6 1 0 0 0 0 5 15 1 0 0 0 0 5 16 1 0 0 0 0 6 7 1 0 0 0 0 6 17 1 0 0 0 0 6 18 1 0 0 0 0 7 8 1 0 0 0 0 7 19 1 0 0 0 0 7 20 1 0 0 0 0 8 9 1 0 0 0 0 8 21 1 0 0 0 0 8 22 1 0 0 0 0 9 23 1 0 0 0 0 9 24 1 0 0 0 0 9 25 1 0 0 0 0 10 14 1 0 0 0 0 M CHG 1 9 1 M END): 16 ms reading 25 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 25 atoms created ModelSet: not autobonding; use forceAutobond=true to force automatic bond creation Script completed Jmol script terminated
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| Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. Lysine contains an α-amino group (which is in the protonated −NH+3 form when the lysine is dissolved in water at physiological pH), an α-carboxylic acid group (which is in the deprotonated −COO− form when the lysine is dissolved in water at physiological pH), and a side chain (CH2)4NH2 (which is partially protonated when the lysine is dissolved in water at physiological pH), and so it is classified as a basic, charged (in water at physiological pH), aliphatic amino acid. It is encoded by the codons AAA and AAG. Like almost all other amino acids, the α-carbon is chiral and lysine may refer to either enantiomer or a racemic mixture of both. For the purpose of this article, lysine will refer to the biologically active enantiomer L-lysine, where the α-carbon is in the S configuration.
The human body cannot synthesize lysine. It is essential in humans and must therefore be obtained from the diet. In organisms that synthesise lysine, two main biosynthetic pathways exist, the diaminopimelate and α-aminoadipate pathways, which employ distinct enzymes and substrates and are found in diverse organisms. Lysine catabolism occurs through one of several pathways, the most common of which is the saccharopine pathway.
Lysine plays several roles in humans, most importantly proteinogenesis, but also in the crosslinking of collagen polypeptides, uptake of essential mineral nutrients, and in the production of carnitine, which is key in fatty acid metabolism. Lysine is also often involved in histone modifications, and thus, impacts the epigenome. The ε-amino group often participates in hydrogen bonding and as a general base in catalysis. The ε-ammonium group (−NH+3) is attached to the fourth carbon from the α-carbon, which is attached to the carboxyl (−COOH) group.
Due to its importance in several biological processes, a lack of lysine can lead to several disease states including defective connective tissues, impaired fatty acid metabolism, anaemia, and systemic protein-energy deficiency. In contrast, an overabundance of lysine, caused by ineffective catabolism, can cause severe neurological disorders.
Lysine was first isolated by the German biological chemist Ferdinand Heinrich Edmund Drechsel in 1889 from hydrolysis of the protein casein, and thus named it Lysin, from Greek λύσις (lysis) 'loosening'. In 1902, the German chemists Emil Fischer and Fritz Weigert determined lysine's chemical structure by synthesizing it.
The one-letter symbol K was assigned to lysine for being alphabetically nearest, with L being assigned to the structurally simpler leucine, and M to methionine.
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Read full article at Wikipedia
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| InChI=1S/C6H14N2O2/c7-4-2-1-3-5(8)6(9)10/h5H,1-4,7-8H2,(H,9,10)/t5-/m0/s1 |
| KDXKERNSBIXSRK-YFKPBYRVSA-N |
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Mus musculus
(NCBI:txid10090)
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Source: BioModels - MODEL1507180067
See:
PubMed
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Chlamydomonas reinhardtii
(NCBI:txid3055)
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See:
PubMed
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Saccharomyces cerevisiae
(NCBI:txid4932)
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See:
PubMed
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Escherichia coli
(NCBI:txid562)
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See:
PubMed
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Escherichia coli
(NCBI:txid562)
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See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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See:
PubMed
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Bronsted base
A molecular entity capable of accepting a hydron from a donor (Bronsted acid).
(via organic amino compound )
Bronsted acid
A molecular entity capable of donating a hydron to an acceptor (Bronsted base).
(via oxoacid )
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micronutrient
Any nutrient required in small quantities by organisms throughout their life in order to orchestrate a range of physiological functions.
algal metabolite
Any eukaryotic metabolite produced during a metabolic reaction in algae including unicellular organisms like chlorella and diatoms to multicellular organisms like giant kelps and brown algae.
mouse metabolite
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
human metabolite
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
Escherichia coli metabolite
Any bacterial metabolite produced during a metabolic reaction in Escherichia coli.
Saccharomyces cerevisiae metabolite
Any fungal metabolite produced during a metabolic reaction in Baker's yeast (Saccharomyces cerevisiae ).
plant metabolite
Any eukaryotic metabolite produced during a metabolic reaction in plants, the kingdom that include flowering plants, conifers and other gymnosperms.
Daphnia magna metabolite
A Daphnia metabolite produced by the species Daphnia magna.
(via lysine )
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nutraceutical
A product in capsule, tablet or liquid form that provide essential nutrients, such as a vitamin, an essential mineral, a protein, an herb, or similar nutritional substance.
anticonvulsant
A drug used to prevent seizures or reduce their severity.
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View more via ChEBI Ontology
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(2S)-2,6-diaminohexanoic acid
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L-lysine
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lysina
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WHO MedNet
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lysine
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WHO MedNet
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lysine
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WHO MedNet
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lysinum
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WHO MedNet
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(S)-2,6-diaminohexanoic acid
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NIST Chemistry WebBook
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(S)-α,ε-diaminocaproic acid
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NIST Chemistry WebBook
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(S)-lysine
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NIST Chemistry WebBook
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6-ammonio-L-norleucine
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PDBeChem
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K
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NIST Chemistry WebBook
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L-2,6-Diaminocaproic acid
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HMDB
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L-Lysin
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ChEBI
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L-Lysine
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KEGG COMPOUND
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Lys
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NIST Chemistry WebBook
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Lysine acid
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KEGG COMPOUND
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1622
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DrugCentral
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C00001378
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KNApSAcK
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C00047
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KEGG COMPOUND
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D02304
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KEGG DRUG
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DB00123
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DrugBank
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ECMDB00182
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ECMDB
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HMDB0000182
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HMDB
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LYS
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MetaCyc
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Lysine
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Wikipedia
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YMDB00330
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YMDB
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| View more database links |
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1722531
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Reaxys Registry Number
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Reaxys
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364182
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Gmelin Registry Number
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Gmelin
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56-87-1
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CAS Registry Number
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KEGG COMPOUND
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56-87-1
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CAS Registry Number
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NIST Chemistry WebBook
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56-87-1
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CAS Registry Number
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ChemIDplus
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Ravi G, Venkatesh YP (2014)
Recognition of flavin mononucleotide, Haemophilus influenzae type b and its capsular polysaccharide vaccines by antibodies specific to D-ribitol-5-phosphate.
Glycoconjugate journal 31, 573-585 [PubMed:25108762]
[show Abstract]
D-Ribitol-5-phosphate (Rbt-5-P) is an important metabolite in the pentose phosphate pathway and an integral part of bacterial cell wall polysaccharides, specifically as polyribosyl ribitol phosphate (PRP) in Haemophilus influenzae type b (Hib). The major objective of this study was to investigate whether an antibody specific to Rbt-5-P can recognize the PRP of Hib. D-Ribose-5-phosphate was reacted with proteins in the presence of sodium cyanoborohydride to obtain Rbt-5-P epitopes; 120 h reaction resulted in conjugation of ~30 and ~17 moles of Rbt-5-P/mole of BSA and OVA, respectively, based on decrease in amino groups, MALDI-TOF analyses, an increase in apparent molecular weight (SDS-PAGE) and glycoprotein staining. Immunization of rabbits with Rbt-5-P-BSA conjugate generated antibodies to Rbt-5-P as demonstrated by dot immunoblot and non-competitive ELISA. Homogeneous Rbt-5-P-specific antibody was purified from Rbt-5-P-BSA antiserum subjected to caprylic acid precipitation followed by hapten-affinity chromatography; its affinity constant is 7.1 × 10(8) M(-1). Rbt-5-P antibody showed 100 % specificity to Rbt-5-P, ~230 %, 10 % and 3.4 % cross-reactivity to FMN, riboflavin and FAD, respectively; the antibody showed ~4 % cross-reactivity to D-ribitol and <3 % to other sugars/sugar alcohols. Rbt-5-P-specific antibody recognized Hib conjugate vaccines containing PRP which was inhibited specifically by Rbt-5-P, and also detected Hib cell-surface capsular polysaccharides by immunofluorescence. In conclusion, Rbt-5-P-protein conjugate used as an immunogen elicited antibodies binding to an epitope also present in PRP and Hib bacteria. Rbt-5-P-specific antibody has potential applications in the detection and quantification of free/bound Rbt-5-P and FMN as well as immunological recognition of Hib bacteria and its capsular polysaccharide. | King ZA, Feist AM (2014)
Optimal cofactor swapping can increase the theoretical yield for chemical production in Escherichia coli and Saccharomyces cerevisiae.
Metabolic engineering 24, 117-128 [PubMed:24831709]
[show Abstract]
Maintaining cofactor balance is a critical function in microorganisms, but often the native cofactor balance does not match the needs of an engineered metabolic flux state. Here, an optimization procedure is utilized to identify optimal cofactor-specificity "swaps" for oxidoreductase enzymes utilizing NAD(H) or NADP(H) in the genome-scale metabolic models of Escherichia coli and Saccharomyces cerevisiae. The theoretical yields of all native carbon-containing molecules are considered, as well as theoretical yields of twelve heterologous production pathways in E. coli. Swapping the cofactor specificity of central metabolic enzymes (especially GAPD and ALCD2x) is shown to increase NADPH production and increase theoretical yields for native products in E. coli and yeast--including L-aspartate, L-lysine, L-isoleucine, L-proline, L-serine, and putrescine--and non-native products in E. coli-including 1,3-propanediol, 3-hydroxybutyrate, 3-hydroxypropanoate, 3-hydroxyvalerate, and styrene. | He L, Yang H, Hou Y, Li T, Fang J, Zhou X, Yin Y, Wu L, Nyachoti M, Wu G (2013)
Effects of dietary L-lysine intake on the intestinal mucosa and expression of CAT genes in weaned piglets.
Amino acids 45, 383-391 [PubMed:23722415]
[show Abstract]
The objective of this study was to evaluate effects of dietary L-lysine on the intestinal mucosa and expression of cationic amino acid transporters (CAT) in weaned piglets. Twenty-eight piglets weaned at 21 days of age (Duroc × Landrace × Yorkshire; 6.51 ± 0.65 kg body weight) were assigned randomly into one of the four groups: Zein + LYS (zein-based diet + 1.35 % supplemental lysine), Zein - LYS (zein-based diet), NF (nitrogen-free diet), and CON (basal diet). The experiment lasted for 3 weeks, during which food intake and body weight were recorded. At the end of the trial, blood was collected from the jugular vein of all pigs, followed by their euthanasia. Dietary supplementation with lysine enhanced villus height and crypt depth in the jejunum (P < 0.05). Jejunal mRNA levels for the b(0,+)-AT, y(+)LAT1 and CAT1 genes were greater (P < 0.05) in the Zein + LYS group than in the control, and the opposite was observed for CAT1. Dietary content of lysine differentially affected intestinal CAT expression to modulate absorption of lysine and other basic amino acids. Thus, transport of these nutrients is a key regulatory step in utilization of dietary protein by growing pigs and lysine in the diet influences the expression of amino acid transporters in the small intestine. | Tsurugizawa T, Uematsu A, Uneyama H, Torii K (2013)
Reversible brain response to an intragastric load of L-lysine under L-lysine depletion in conscious rats.
The British journal of nutrition 109, 1323-1329 [PubMed:23167968]
[show Abstract]
L-Lysine (Lys) is an essential amino acid and plays an important role in anxiogenic behaviour in both human subjects and rodents. Previous studies have shown the existence of neural plasticity between the Lys-deficient state and the normal state. Lys deficiency causes an increase in noradrenaline release from the hypothalamus and serotonin release from the amygdala in rats. However, no studies have used functional MRI (fMRI) to compare the brain response to ingested Lys in normal, Lys-deficient and Lys-recovered states. Therefore, in the present study, using acclimation training, we performed fMRI on conscious rats to investigate the brain response to an intragastric load of Lys. The brain responses to intragastric administration of Lys (3 mmol/kg body weight) were investigated in six rats intermittently in three states: normal, Lys-deficient and recovered state. First, in the normal state, an intragastric load of Lys activated several brain regions, including the raphe pallidus nucleus, prelimbic cortex and the ventral/lateral orbital cortex. Then, after 6 d of Lys deprivation from the normal state, an intragastric load of Lys activated the ventral tegmental area, raphe pallidus nucleus and hippocampus, as well as several hypothalamic areas. After recovering from the Lys-deficient state, brain activation was similar to that in the normal state. These results indicate that neural plasticity in the prefrontal cortex, hypothalamic area and limbic system is related to the internal Lys state and that this plasticity could have important roles in the control of Lys intake. | Ruane KM, Lloyd AJ, Fülöp V, Dowson CG, Barreteau H, Boniface A, Dementin S, Blanot D, Mengin-Lecreulx D, Gobec S, Dessen A, Roper DI (2013)
Specificity determinants for lysine incorporation in Staphylococcus aureus peptidoglycan as revealed by the structure of a MurE enzyme ternary complex.
The Journal of biological chemistry 288, 33439-33448 [PubMed:24064214]
[show Abstract]
Formation of the peptidoglycan stem pentapeptide requires the insertion of both L and D amino acids by the ATP-dependent ligase enzymes MurC, -D, -E, and -F. The stereochemical control of the third position amino acid in the pentapeptide is crucial to maintain the fidelity of later biosynthetic steps contributing to cell morphology, antibiotic resistance, and pathogenesis. Here we determined the x-ray crystal structure of Staphylococcus aureus MurE UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:meso-2,6-diaminopimelate ligase (MurE) (E.C. 6.3.2.7) at 1.8 Å resolution in the presence of ADP and the reaction product, UDP-MurNAc-L-Ala-γ-D-Glu-L-Lys. This structure provides for the first time a molecular understanding of how this Gram-positive enzyme discriminates between L-lysine and D,L-diaminopimelic acid, the predominant amino acid that replaces L-lysine in Gram-negative peptidoglycan. Despite the presence of a consensus sequence previously implicated in the selection of the third position residue in the stem pentapeptide in S. aureus MurE, the structure shows that only part of this sequence is involved in the selection of L-lysine. Instead, other parts of the protein contribute substrate-selecting residues, resulting in a lysine-binding pocket based on charge characteristics. Despite the absolute specificity for L-lysine, S. aureus MurE binds this substrate relatively poorly. In vivo analysis and metabolomic data reveal that this is compensated for by high cytoplasmic L-lysine concentrations. Therefore, both metabolic and structural constraints maintain the structural integrity of the staphylococcal peptidoglycan. This study provides a novel focus for S. aureus-directed antimicrobials based on dual targeting of essential amino acid biogenesis and its linkage to cell wall assembly. | Prolla IR, Rafii M, Courtney-Martin G, Elango R, da Silva LP, Ball RO, Pencharz PB (2013)
Lysine from cooked white rice consumed by healthy young men is highly metabolically available when assessed using the indicator amino acid oxidation technique.
The Journal of nutrition 143, 302-306 [PubMed:23325920]
[show Abstract]
Cooked white rice (CWR) provides up to 71% of the dietary protein for many people worldwide. The protein digestibility-corrected amino acid (AA) score is the method adopted by FAO/WHO to evaluate protein quality. Our group has proposed the metabolic availability (MA) of AAs as another determinant of protein quality. It measures the percentage of an indispensable AA that is incorporated during protein synthesis. This study is the first to our knowledge to assess the MA of l-lysine (L-Lys) from CWR in humans using the indicator AA oxidation (IAAO) technique. Three amounts of L-Lys, 10, 15, and 19 mg · kg(-1) · d(-1) (= 28.5, 42.8, and 54.3% of the mean L-Lys requirement of 35 mg · kg(-1) · d(-1)), were studied in 5 healthy young men in a repeated-measures design. To test the principle that the Maillard reaction has an effect on the MA of LLys, we also assessed the MA of L-Lys in oven-browned, cooked rice (n = 3) in the amount of 19 mg · kg(-1) · d(-1) L-Lys. The MA of L-Lys was estimated by comparing the IAAO response with varying L-Lys intakes in rice compared with the IAAO response to varying l-Lys intakes in the reference protein (crystalline AA mixture patterned after egg protein) using the slope ratio method. The MA of L-Lys from CWR was high (97%), but the effect of the Maillard reaction reduced it to 70%. The results show that despite its relatively low content in rice, L-Lys has a high MA when the rice is cooked without being browned. | Usha R, Sreeram KJ, Rajaram A (2012)
Stabilization of collagen with EDC/NHS in the presence of L-lysine: a comprehensive study.
Colloids and surfaces. B, Biointerfaces 90, 83-90 [PubMed:22019452]
[show Abstract]
This paper reports the effect of L-lysine on the conformational, rheological, and thermal properties of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) cross linked collagen and investigates the influence of l-lysine on the self assembly processes of collagen. In the absence of L-lysine, the rheological characterization of collagen cross linked with EDC/NHS showed an increase in shearing stress with shearing speed indicating that the collagen chains become rigid and the molecules are reluctant to flow. On the other hand, the increase in shearing stress with shearing speed is comparatively much less in the presence of L-lysine indicating a greater flexibility of the collagen molecules. The self assembly processes of collagen treated with EDC/NHS in the absence and presence of L-lysine were characterized using powder XRD, FT-IR, polarizing optical microscopy and kinetic studies. XRD studies show an increase in peak intensity and sharpness in the presence of L-lysine indicating the enhancement of crystallinity of collagen nano-fibrils. FT-IR results suggest that the incorporation of L-lysine in the EDC/NHS cross linking favors the molecular stability of collagen. From the present study, it is possible to conclude that the pre-treatment of collagen with L-lysine enhances EDC/NHS cross linking and can be used for biomaterial applications. | Woodward AD, Fan MZ, Geor RJ, McCutcheon LJ, Taylor NP, Trottier NL (2012)
Characterization of L-lysine transport across equine and porcine jejunal and colonic brush border membrane.
Journal of animal science 90, 853-862 [PubMed:22064742]
[show Abstract]
In nonruminant herbivores, microbially derived AA could contribute to whole-body AA homeostasis and thus decrease predicted AA requirements. However, postileal capacity of AA uptake is currently unknown. Therefore, to test the hypothesis that Lys is transported across the large colon mucosal apical membrane with capacity similar to that of the small intestinal mucosa in the pony and pig, we examined Lys transport in vitro using brush border membrane vesicles (BBMV). Mucosa was collected from the distal jejunum (DJ) and proximal large colon (PLC) of growing pigs (n = 3) and ponies (n = 4), flash frozen in liquid nitrogen, and stored at -80°C. Jejunal and colonic BBMV were manufactured by Mg(2+) precipitation and used to determine initial rates and kinetics [the maximal transport rate (V(max)) and the Michaelis constant (K(M))] of l-Lys transport into apical epithelia by rapid filtration technique in Na(+)-gradient incubation buffer. Initial rates of total l-Lys uptake did not differ between the PLC and DJ in either the pig or the pony, or between the pony and the pig, at each l-Lys concentration. In the pig, compared with the DJ, l-Lys transport V(max) in the PLC did not differ (121 ± 26 and 180 ± 26 pmol•mg of protein(-1)•s(-1), respectively; P = 0.14) and l-Lys K(M) in the PLC tended to be greater (0.23 ± 0.22 and 0.89 ± 0.22 mM, respectively; P = 0.09). In the pony, compared with the DJ, l-Lys transport V(max) in the PLC was greater (62 ± 25 and 149 ± 25 pmol•mg of protein(-1)•s(-1), respectively; P = 0.04) and l-Lys K(M) in the PLC was greater (0.08 ± 0.22 and 1.05 ± 0.22 mM, respectively; P = 0.02). l-Lysine diffusion was not different between segments; however, total intestinal diffusion was greater (P = 0.03) in the pony than in the pig (115 ± 10 and 73 ± 10 pmol·mg of protein(-1)•s(-1), respectively). These results demonstrate that the large colon is capable of l-Lys transport across the apical epithelial membrane with greater capacity and less affinity than the jejunum, indicating that the large colon may play a significant role in l-Lys absorption and homeostasis in hindgut fermenters. | Bordbar A, Mo ML, Nakayasu ES, Schrimpe-Rutledge AC, Kim YM, Metz TO, Jones MB, Frank BC, Smith RD, Peterson SN, Hyduke DR, Adkins JN, Palsson BO (2012)
Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation.
Molecular systems biology 8, 558 [PubMed:22735334]
[show Abstract]
Macrophages are central players in immune response, manifesting divergent phenotypes to control inflammation and innate immunity through release of cytokines and other signaling factors. Recently, the focus on metabolism has been reemphasized as critical signaling and regulatory pathways of human pathophysiology, ranging from cancer to aging, often converge on metabolic responses. Here, we used genome-scale modeling and multi-omics (transcriptomics, proteomics, and metabolomics) analysis to assess metabolic features that are critical for macrophage activation. We constructed a genome-scale metabolic network for the RAW 264.7 cell line to determine metabolic modulators of activation. Metabolites well-known to be associated with immunoactivation (glucose and arginine) and immunosuppression (tryptophan and vitamin D3) were among the most critical effectors. Intracellular metabolic mechanisms were assessed, identifying a suppressive role for de-novo nucleotide synthesis. Finally, underlying metabolic mechanisms of macrophage activation are identified by analyzing multi-omic data obtained from LPS-stimulated RAW cells in the context of our flux-based predictions. Our study demonstrates metabolism's role in regulating activation may be greater than previously anticipated and elucidates underlying connections between activation and metabolic effectors. | Mirmiranpour H, Bathaie SZ, Khaghani S, Nakhjavani M, Kebriaeezadeh A (2012)
Investigation of the mechanism(s) involved in decreasing increased fibrinogen activity in hyperglycemic conditions using L-lysine supplementation.
Thrombosis research 130, e13-9 [PubMed:22575419]
[show Abstract]
IntroductionFibrinogen is a plasma glycoprotein that participates in the hemostasis system. Its malfunction has been reported as a consequence of diabetic complications. In this study, the inhibitory effect of L-Lysine (Lys) on the nonenzymatic glycation of fibrinogen was investigated in both in vitro and in vivo conditions.Materials and methodsFibrinogen was incubated with glucose in the presence or absence of Lys. Then, its structure was studied by fluorescence spectroscopy, circular dichroism, and electrophoresis. The Clauss method was used to determine fibrinogen activity. In addition, one of the two groups of type 2 diabetic patients receiving ordinary treatment was additionally treated with Lys for 3 months. Fibrinogen activity and some other parameters were evaluated in their plasma.ResultsThe results indicated increases in the activity of glycated fibrinogen in both of the in vivo and in vitro experiments. Advanced glycation end products were increased by time, as shown using fluorometry in both the plasma of the diabetic patients and the incubation medium of protein with glucose. The circular dichroism spectra showed some changes in the fibrinogen secondary and tertiary structures after glycation. The electrophoretic mobility of the glycated fibrinogen changed and the cross-link formation between the fibrinogen subunits due to glycation was observed. Lys inhibited all of the mentioned fibrinogen changes both in the in vitro experiments and after its administration to the diabetic patients.ConclusionLys, as an inhibitor of protein glycation, improved fibrinogen's structure and function, both in vitro and in vivo. | Sreenath K, Venkatesh YP (2007)
Reductively aminated D-xylose-albumin conjugate as the immunogen for generation of IgG and IgE antibodies specific to D-xylitol, a haptenic allergen.
Bioconjugate chemistry 18, 1995-2003 [PubMed:17979222]
[show Abstract]
Sugar alcohols are widely used as food additives and drug excipients. Xylitol, a five-carbon sugar alcohol, and a low-calorie alternative sweetener to sucrose (approx 40% fewer calories), has enjoyed an enviable record of safety, and allergic reactions to xylitol are very rare. A case of oral erosive eczema to xylitol has been reported recently [Hanakawa, Y., Hanakawa, Y., Tohyama, M., Yamasaki, K., Hashimoto, K. (2005) Xylitol as a causative agent of oral erosive eczema. Brit. J. Dermatol. 152, 821-822]. Xylitol does not contain any reactive groups; hence, it is nonimmunogenic. In order to explain the immunogenicity of xylitol, polyclonal antibodies to xylitol have been raised using the reductive aminated product of D-xylose conjugated to bovine serum albumin (BSA) as the immunogen. Rabbits immunized with xylitol-BSA conjugate (52 haptens/molecule) gave a good antibody response. Purification of antixylitol antibodies was carried out using hapten-affinity chromatography on xylitol-keyhole limpet hemocyanin-Sepharose CL-6B; the yield was approximately 40 microg/mL of rabbit immune serum. Purified xylitol-specific antibodies appeared to be homogeneous by native PAGE with a pI of approximately 7.2 by isoelectric focusing. Although the purified antibodies are specific for the xylitoyl moiety of xylitol-protein conjugates, they reacted equally well with the Schiff base conjugate of xylosyl-protein conjugates (68% cross-reactivity) indicating that carbons 2 to 5 of xylitol act as an epitope. Xylitol antibodies showed excellent specificity towards xylitol and <4.4% cross-reactivity with D-xylose and various sugar alcohols except ribitol and galactitol, which showed approximately 11% and 8% cross-reactivity, respectively. D-Xylitol-BSA conjugate was used to raise IgE antibodies in BALB/c mice by repeated intradermal administration. Passive cutaneous anaphylaxis using the immune sera confirmed the haptenic nature of xylitol. | Sreenath K, Prabhasankar P, Venkatesh YP (2006)
Generation of an antibody specific to erythritol, a non-immunogenic food additive.
Food additives and contaminants 23, 861-869 [PubMed:16901854]
[show Abstract]
Erythritol, a simple sugar alcohol, is widely used as a food and drug additive owing to its chemical inertness, sweetness and non-toxicity. Adverse reactions to erythritol are rare and only three cases of allergic reactions to foods containing erythritol have been reported. Being inert, erythritol cannot produce an immunological response. In order to explain the mechanism of immunogenicity of erythritol, a method to obtain erythritol epitopes on a carrier protein, which can serve as an immunogen to develop antibodies against erythritol, is described. D-Erythrose was conjugated to bovine serum albumin at pH 8 by reductive amination. The reduction product of the Schiff base of D-erythrose-bovine serum albumin conjugate creates erythritoyl groups. Rabbits immunized with erythritol-bovine serum albumin conjugate (29 haptens/molecule) showed good antibody response (detection of 1 microg antigen, erythritol-keyhole limpet haemocyanin conjugate possessing 50% modified amino groups, at 1 : 50,000 dilution). Anti-erythritol immunoglobulin-G antibodies were purified from the immune serum using hapten-affinity chromatography on an erythritol-keyhole limpet haemocyanin-Sepharose CL-6B affinity matrix. The yield of erythritol-specific antibody was approximately 40 microg ml-1 of rabbit antiserum. Enzyme-linked immunobsorbant assay inhibition studies using sugars, sugar alcohols and L-lysine showed minimal cross-reactivity (approximately 4%) when compared with erythritol; only dithioerythritol showed a cross-reactivity of approximately 33%. D-Threitol and L-threitol (isomers of erythritol) had cross-reactivities of 15 and 11%, respectively. The inhibition studies confirmed the haptenic nature of erythritol and indicated that the erythritoyl group is a single epitope. The reaction scheme outlined here for the generation of erythritol epitopes appears to provide a basis for the immunogenicity of erythritol. | Long JH, Lira VA, Soltow QA, Betters JL, Sellman JE, Criswell DS (2006)
Arginine supplementation induces myoblast fusion via augmentation of nitric oxide production.
Journal of muscle research and cell motility 27, 577-584 [PubMed:17051348]
[show Abstract]
The semi-essential amino acid, L-arginine (L-Arg), is the substrate for endogenous synthesis of nitric oxide, a molecule that is involved in myoblast proliferation and fusion. Since L-Arg supply may limit nitric oxide synthase (NOS) activity in endothelial cells, we examined L-Arg supplementation in differentiating mouse myoblasts and tested the hypothesis that L-Arg exerts direct effects on myoblast fusion via augmentation of endogenous nitric oxide production. C(2)C(12) myoblasts in differentiation media received one of the following treatments for 120 h: 1 mM L-Arg, 0.1 mM N-nitro-L-arginine methyl ester (L-NAME), L-Arg + L-NAME, 10 mM L-Lysine, or no supplement (Control). Cultures were fixed and stained with hematoxylin and eosin for microphotometric image analysis of myotube density, nuclear density, and fusion index (% of total nuclei in myotubes). Endogenous production of nitric oxide during the treatment period peaked between 24 and 48 h. L-Arg amplified nitric oxide production between 0 and 24 h and increased myotube density, total nuclei number, and nuclear fusion index. These L-Arg effects were prevented by the NOS inhibitor, L-NAME. Further, L-Lysine, a competitive inhibitor of L-Arg uptake, repressed nitric oxide production and reduced myotube density and fusion index. In summary, L-Arg augments myotube formation and increases nitric oxide production in a process limited by cellular L-Arg uptake. | Zhao Z, Baldo BA, O'Brien RM, Plomley RF (2000)
Reaction with, and fine structural recognition of polyamines by human IgE antibodies.
Molecular immunology 37, 233-240 [PubMed:10930630]
[show Abstract]
Human IgE antibodies from nine allergic subjects were found to react with poly-L-lysine (PLL) and other polyamines. Radioimmunoassay inhibition studies indicated that the two amino groups, but not the carboxyl, in lysine contributed to the antibody binding and 4-aminomethyl-1,8-octanediamine, a compound containing three primary amino groups, was a better inhibitor than compounds containing only two primary amino groups. Ethylamine showed weak but clear inhibition indicating that even a single amino group could bind to the antibody combining site. Substituted ethanolamine and quaternary ammonium compounds were well recognized by some sera but with others, substitution hampered recognition. Inhibition studies with compounds containing an amino and a carboxyl group at different distances revealed that an adjacent carboxyl group interfered with recognition of the amino group by some IgE antibodies. IgE binding to PLL was examined at different pHs and ionic strengths. Binding was greatest at pH 5-6 to 8 and decreased markedly outside this range. Ionic strengths higher than 0.3 M significantly diminished the binding. These results indicated that binding of specific antibody to polyamine was due to electrostatic interactions of positively charged amino groups in the polyamine with the antibody combining site. These results may be relevant to mechanisms underlying recognition of some allergens in some atopic conditions. | Chang YF, Gao XM (1995)
L-lysine is a barbiturate-like anticonvulsant and modulator of the benzodiazepine receptor.
Neurochemical research 20, 931-937 [PubMed:8587651]
[show Abstract]
Our earlier observations showed that L-lysine enhanced the activity of diazepam against seizures induced by pentylenetetrazol (PTZ), and increased the affinity of benzodiazepine receptor binding in a manner additive to that caused by gamma-aminobutyric acid (GABA). The present paper provides additional evidence to show that L-lysine has central nervous system depressant-like characteristics. L-lysine enhanced [3H]flunitrazepam (FTZ) binding in brain membranes was dose-dependent and stimulated by chloride, bromide and iodide, but not fluoride. Enhancement of [3H]FTZ binding by L-lysine at a fixed concentration was increased by GABA but inhibited by pentobarbital between 10(-7) to 10(-3)M. While GABA enhancement of [3H]FTZ binding was inhibited by the GABA mimetics imidazole acetic acid and tetrahydroisoxazol pyridinol, the enhancement by pentobarbital and L-lysine of [3H]FTZ binding was dose-dependently increased by these two GABA mimetics. The above results suggest that L-lysine and pentobarbital acted at the same site of the GABA/benzodiazepine receptor complex which was different from the GABA binding site. The benzodiazepine receptor antagonist imidazodiazepine Ro15-1788 blocked the antiseizure activity of diazepam against PTZ. Similar to pentobarbital, the anti-PTZ effect of L-lysine was not blocked by Ro15-1788. Picrotoxinin and the GABA, receptor antagonist bicuculline partially inhibited L-lysine's enhancement of [3H]FTZ binding with the IC50s of 2 microM and 0.1 microM, respectively. The convulsant benzodiazepine Ro5-3663 dose-dependently inhibited the enhancement of [3H]FTZ binding by L-lysine. This article shows the basic amino acid L-lysine to have a central nervous system depressant characteristics with an anti-PTZ seizure activity and an enhancement of [3H]FTZ binding similar to that of barbiturates but different from GABA. | Taneda S, Monnier VM (1994)
ELISA of pentosidine, an advanced glycation end product, in biological specimens.
Clinical chemistry 40, 1766-1773 [PubMed:8070089]
[show Abstract]
Pentosidine is a fluorescent protein cross-link and glycoxidation marker for the advanced glycation reaction in diabetes, aging, and uremia. We raised polyclonal antibodies in New Zealand White rabbits against this hapten coupled to keyhole limpet hemocyanin. The antibodies detected by ELISA reacted strongly with free pentosidine but not with pentosidine-like compounds. The working range of the competitive ELISA for standard pentosidine was 0.1-100 pmol. Pentosidine was detectable in bovine serum albumin incubated with ribose as a function of incubation time. Immunoblotting studies showed that pentosidine specifically stained in oligomers of lysozyme incubated with ribose. Digestion with protease (Pronase E, 20 g/kg) as well as acid hydrolysis enhanced the immunoreactivity of samples, the pentosidine values in digested human plasma correlating with those measured by HPLC (r = 0.98). Pentosidine in diabetic and uremic plasma digested with Pronase E was significantly higher than normal (P < 0.01; mean +/- SD): 1620 +/- 1940 and 2630 +/- 1320 [corrected] nmol/L, respectively, vs 151 +/- 55 nmol/L (normal). Amounts of pentosidine in hydrolyzed skin collagen increased with age and were increased in diabetes and uremia. This ELISA provides a new tool for assessing the role of the advanced Maillard reaction in aging and age-related diseases. |
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