Queuine
Identification
- Generic Name
- Queuine
- DrugBank Accession Number
- DB14732
- Background
Queuine is a derivative of 7-Deazaguanine. Bacteria possess the exclusive ability to synthesize queuine, which is then salvaged and passed on to plants and animals. Quantities of queuine have been found in tomatoes, wheat, coconut water, and milk from humans, cows, and goats. Humans salvage and recover queuine from either ingested food or the gut flora. All eukaryotic organisms, including humans, transform queuine to queuosine by placing it in the wobble position (anticodon) of several tRNAs including aspartic acid, asparagine, histidine, and tyrosine. Endogenously, it has been determined that queuine contributes to generating various important biochemicals like tyrosine, serotonin, dopamine, epinephrine, norepinephrine, nitric oxide, lipids, and others 1,2,3.
- Type
- Small Molecule
- Groups
- Experimental, Nutraceutical
- Structure
- Weight
- Average: 277.2792
Monoisotopic: 277.117489371 - Chemical Formula
- C12H15N5O3
- Synonyms
- 7-(3,4-trans-4,5-cis-dihydroxy-1-cyclopenten-3-ylaminomethyl)-7-deazaguanine
- Base Q
- Q Base
Pharmacology
- Indication
Current and on-going research suggests queuine is a natural biochemical compound that can be found endogenously in the human body and plays an essential role in the generation of other critical bodily chemicals including tyrosine, serotonin, dopamine, epinephrine, norepinephrine, nitric oxide, lipids, and others 1,2,3. Such research subsequently proposes that if queuine could be utilized as a pharmaceutic, that it may be considered a so-called 'putative longevity vitamin' indicated for age-delaying and/or prolonged survival functionality (perhaps via maintaining the ongoing generation of the aforementioned bodily chemicals) for the human body 1,2,3.
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- Pharmacodynamics
Studies have demonstrated that a deficiency in queuine in in-vitro human cells and in animals results in a decreased level of the cofactor tetrahydrobiopterin (BH4) 1,2. Since BH4 is a necessary cofactor for the transformation of phenylalanine to tyrosine, of tryptophan to serotonin, of tyrosine to dopamine (dopamine, which itself is further converted into epinephrine and norepinephrine), of arginine to nitric oxide, and for the oxidation of alkyl glycerol lipids 1,2, it is proposed that queuine plays an important pharmacodynamic role in the generation and maintenance of these essential biochemical compounds 1,2,3.
- Mechanism of action
Certain studies have shown that queuine-deficient mice became tyrosine deficient and expired within eighteen days of being withdrawn from a queuine containing diet 2. Considering tyrosine is generally a nonessential amino acid, it is presumed that the expiration of the mice was due to a resultant deficiency in the cofactor tetrahydrobiopterin (BH4) (which does contribute to the generation of tyrosine), the endogenous generation of which queuine is believed to contribute to 1,2. As a result, one of the potential mechanisms of action by which queuine may act as a vitamin for age-delaying and/or prolonged survival functionality speaks to the plausible essentiality of BH4 for partaking in activities like the hydroxylation of tryptophan to produce serotonin for numerous neurological functions like controlling executive function and playing a part in the pathophysiology of autism, attention-deficit/hyperactivity, bipolar, and schizophrenia disorders 1,2.
Elsewhere, another study has also demonstrated that queuine and the use of a synthetic analog have been effective in eliciting full remission in a mouse model of multiple sclerosis, particularly via the importance of tRNA guanine transglycosylase (TGT) present in the animal model to utilize the queuine analog substrate 2,3. Essentially, animals deficient in TGT are incapable of using queuine or any synthetic analog of the biochemical to modify tRNA to produce queuosine for further related downstream pharmacodynamics and fail to respond to such therapy 2,3. Although the specific mechanism of action beyond these actions has not yet been formally elucidated, these actions suggest that some manner of modulation of protein translation may be the principal means via which this therapeutic effect is elicited 2,3.
In human cells, queuine tRNA-ribosyltransferase (QTRT-1) interacts with queuine tRNA-ribosyltransferase subunit QTRTD1 to form an active queuine tRNA-ribosyltransferase 1,2,3,4. This enzyme exchanges queuine for the guanine at the wobble position of tRNAs with GU(N) anticodons (tRNA-Asp, -Asn, -His and -Tyr), thereby forming the hypermodified nucleoside queuosine 1,2,3,4.
- Absorption
Humans recover queuine from either ingested food or the gut flora 1,2,3. The proportion of queuine salvaged and absorbed from the normal turnover process of human microbiota has not yet been determined, but it may be significant given the number of microorganisms in the human gastrointestinal tract 1. Furthermore, it is believed that there may exist a dedicated transporter for queuine, considering various purines, purine-derivatives and base analogs are incapable of affecting queuine transport in competitive uptake experiments 1,2.
- Volume of distribution
Data regarding the volume of distribution of queuine is not readily available or accessible.
- Protein binding
Data regarding the protein binding of queuine is not readily available or accessible.
- Metabolism
Data regarding the metabolism of queuine is not readily available or accessible.
- Route of elimination
Data regarding the route of elimination of queuine is not readily available or accessible.
- Half-life
Data regarding the half-life of queuine is not readily available or accessible.
- Clearance
Data regarding the clearance of queuine is not readily available or accessible.
- Adverse Effects
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- Toxicity
Queuine is a natural biochemical that can be found endogenously in the human body 1,2,3. Although certain studies on mouse models have shown that a deficiency in the agent can have fatal consequences 1,2,3, data regarding toxicity or overdosage of queuine is not readily available or accessible.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyrrolo[2,3-d]pyrimidines. These are aromatic heteropolycyclic compounds containing a pyrrolo[2,3-d]pyrimidine ring system, which is an pyrrolopyrimidine isomers having the 3 ring nitrogen atoms at the 1-, 5-, and 7-positions.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyrrolopyrimidines
- Sub Class
- Pyrrolo[2,3-d]pyrimidines
- Direct Parent
- Pyrrolo[2,3-d]pyrimidines
- Alternative Parents
- Hydroxypyrimidines / Aralkylamines / Substituted pyrroles / Heteroaromatic compounds / Secondary alcohols / 1,2-diols / Dialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
- Substituents
- 1,2-diol / Alcohol / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Heteroaromatic compound / Hydrocarbon derivative / Hydroxypyrimidine / Organic nitrogen compound
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- pyrrolopyrimidine (CHEBI:17433)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- DAK6EYX2BZ
- CAS number
- 72496-59-4
- InChI Key
- WYROLENTHWJFLR-ACLDMZEESA-N
- InChI
- InChI=1S/C12H15N5O3/c13-12-16-10-8(11(20)17-12)5(4-15-10)3-14-6-1-2-7(18)9(6)19/h1-2,4,6-7,9,14,18-19H,3H2,(H4,13,15,16,17,20)/t6-,7-,9+/m0/s1
- IUPAC Name
- (1R,2S,5S)-5-[({4-hydroxy-2-imino-1H,2H,7H-pyrrolo[2,3-d]pyrimidin-5-yl}methyl)amino]cyclopent-3-ene-1,2-diol
- SMILES
- NC1=NC2=C(C(CN[C@H]3C=C[C@H](O)[C@@H]3O)=CN2)C(=O)N1
References
- General References
- Fergus C, Barnes D, Alqasem MA, Kelly VP: The queuine micronutrient: charting a course from microbe to man. Nutrients. 2015 Apr 15;7(4):2897-929. doi: 10.3390/nu7042897. [Article]
- Ames BN: Prolonging healthy aging: Longevity vitamins and proteins. Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):10836-10844. doi: 10.1073/pnas.1809045115. Epub 2018 Oct 15. [Article]
- Varghese S, Cotter M, Chevot F, Fergus C, Cunningham C, Mills KH, Connon SJ, Southern JM, Kelly VP: In vivo modification of tRNA with an artificial nucleobase leads to full disease remission in an animal model of multiple sclerosis. Nucleic Acids Res. 2017 Feb 28;45(4):2029-2039. doi: 10.1093/nar/gkw847. [Article]
- The Human Metabolome Database: Queuine Profile [Link]
- External Links
- Human Metabolome Database
- HMDB0001495
- KEGG Compound
- C01449
- ChemSpider
- 102837
- ChEBI
- 17433
- ZINC
- ZINC000006622451
- PDBe Ligand
- QEI
- Wikipedia
- Queuine
- PDB Entries
- 3blo / 4hqv / 4hsh / 4hvx / 6h45 / 7ovo / 7owz / 8dl3
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.59 mg/mL ALOGPS logP -1.6 ALOGPS logP -2.6 Chemaxon logS -2.7 ALOGPS pKa (Strongest Acidic) 1.95 Chemaxon pKa (Strongest Basic) 21.26 Chemaxon Physiological Charge 1 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 7 Chemaxon Polar Surface Area 136.75 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 83.97 m3·mol-1 Chemaxon Polarizability 27.42 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-003r-0980000000-6d9e1b1abdb7afef0800 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-01sm-0490000000-8e15323512ce7d157f4b Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-0190000000-a2d2ef6380af5d10689b Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-03k9-0940000000-d611a27c8b081cdf9a83 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-0490000000-0bd6e3b2961c28441916 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-01po-3910000000-4fdee342c805d54d8cb8 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 175.1274714 predictedDarkChem Lite v0.1.0 [M-H]- 159.63536 predictedDeepCCS 1.0 (2019) [M+H]+ 173.7194714 predictedDarkChem Lite v0.1.0 [M+H]+ 162.03093 predictedDeepCCS 1.0 (2019) [M+Na]+ 173.9484714 predictedDarkChem Lite v0.1.0 [M+Na]+ 168.4576 predictedDeepCCS 1.0 (2019)
Enzymes
- Kind
- Protein
- Organism
- Zymomonas mobilis subsp. mobilis (strain ATCC 31821 / ZM4 / CP4)
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Queuine trna-ribosyltransferase activity
- Specific Function
- Exchanges the guanine residue with 7-aminomethyl-7-deazaguanine in tRNAs with GU(N) anticodons (tRNA-Asp, -Asn, -His and -Tyr). After this exchange, a cyclopentendiol moiety is attached to the 7-am...
- Gene Name
- tgt
- Uniprot ID
- P28720
- Uniprot Name
- Queuine tRNA-ribosyltransferase
- Molecular Weight
- 42842.235 Da
References
- Fergus C, Barnes D, Alqasem MA, Kelly VP: The queuine micronutrient: charting a course from microbe to man. Nutrients. 2015 Apr 15;7(4):2897-929. doi: 10.3390/nu7042897. [Article]
- Ames BN: Prolonging healthy aging: Longevity vitamins and proteins. Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):10836-10844. doi: 10.1073/pnas.1809045115. Epub 2018 Oct 15. [Article]
- Varghese S, Cotter M, Chevot F, Fergus C, Cunningham C, Mills KH, Connon SJ, Southern JM, Kelly VP: In vivo modification of tRNA with an artificial nucleobase leads to full disease remission in an animal model of multiple sclerosis. Nucleic Acids Res. 2017 Feb 28;45(4):2029-2039. doi: 10.1093/nar/gkw847. [Article]
- The Human Metabolome Database: Queuine Profile [Link]
Drug created at January 14, 2019 21:51 / Updated at June 12, 2020 16:53