Identification

Name
Queuine
Accession Number
DB14732
Description

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
Thumb
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

Pharmacology
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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.

Contraindications & Blackbox Warnings
Contraindications
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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.

Affected organisms
  • Humans and other mammals
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)

Chemical Identifiers

UNII
Not Available
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
  1. 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. [PubMed:25884661]
  2. 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. [PubMed:30322941]
  3. 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. [PubMed:28204548]
  4. The Human Metabolome Database: Queuine Profile [Link]
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

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

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
PropertyValueSource
Water Solubility0.59 mg/mLALOGPS
logP-1.6ALOGPS
logP-2.6ChemAxon
logS-2.7ALOGPS
pKa (Strongest Acidic)1.95ChemAxon
pKa (Strongest Basic)21.26ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area136.75 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity83.97 m3·mol-1ChemAxon
Polarizability27.42 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-01t9-0490000000-79c2ee42b531999a48da
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-0940000000-3b8adbd9aa0d46707a89
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-2900000000-1cda697801b74c63eb78
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0290000000-7248e6280feb27a6b9e4
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-002b-2790000000-6bcdd7a8145915cadc8a
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-052e-4900000000-2ac324bda4a707569cce

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
  1. 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. [PubMed:25884661]
  2. 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. [PubMed:30322941]
  3. 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. [PubMed:28204548]
  4. The Human Metabolome Database: Queuine Profile [Link]

Drug created on January 14, 2019 21:51 / Updated on June 12, 2020 16:53