Queuine

Queuine
Names
Preferred IUPAC name
2-Amino-5-({[(1S,4S,5R)-4,5-dihydroxycyclopent-2-en-1-yl]amino}methyl)-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one
Other names
7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deazaguanine
Identifiers
3D model (JSmol)
ChemSpider
MeSH Queuine
UNII
  • 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 ☒N
    Key: WYROLENTHWJFLR-ACLDMZEESA-N ☒N
  • InChI=1/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
    Key: WYROLENTHWJFLR-ACLDMZEEBO
  • C1=C[C@@H]([C@@H]([C@H]1NCC2=CNC3=C2C(=O)NC(=N3)N)O)O
Properties
C12H15N5O3
Molar mass 277.284 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Queuine (/kjuːiːn/) (Q) is a hypermodified nucleobase found in the first (or wobble) position of the anticodon of tRNAs specific for Asn, Asp, His, and Tyr, in most eukaryotes and prokaryotes.[1] Because it is utilized by all eukaryotes but produced exclusively by bacteria, it is a putative vitamin.[2]

The nucleoside of queuine is queuosine. Queuine is not found in the tRNA of archaea; however, a related 7-deazaguanine derivative, the nucleoside of which is archaeosine, occurs in different tRNA position, the dihydrouridine loop, and in tRNAs with more specificities.

History and naming

In 1967, it was discovered that the four above-mentioned tRNAs contained an as-yet unknown nucleoside, which was designated "Nucleoside Q". This name remained in use throughout much of the work to characterize the compound, after which it was proposed that its common name should be based on the sound of the letter Q—thus producing "queuine" by analogy to guanine and other nucleobases, and "queuosine" by analogy to guanosine and other nucleosides.[3]

Biosynthesis and function

The presence of queuine in certain tRNA is a nearly ubiquitous feature of eukaryotic life, meaning it is found in every healthy cell of the human body. It is also found in all other animals, plants, and fungi. The only known exception is brewer's yeast, Saccharomyces cerevisiae. However, queuosine can be produced only by bacteria; higher organisms must obtain queuine from the diet, or salvage it from symbiotic microbes: a process for which dedicated enzymatic machinery exists.[4] Because queuine is necessary for healthy cellular function in animals, but is produced exclusively by microbes, it can be considered a vitamin, akin to the B vitamins—many which are also produced primarily or exclusively by bacteria.[5]

The biosynthesis pathway for queuine shares a common enzymatic starting step with folate. Because queuosine in dietary or gut-bacterial RNA can be salvaged and converted to queuine by the human body, queuosine could be considered a vitamer of queuine. As of 2019, human queuine requirements are not well understood, and the prevalence of queuine deficiency in humans is unknown.[6] Plants obtain queuine from the tRNA of symbiotic bacteria in and around their roots.

Once salvaged, queuine replaces a guanine base in the anticodon of certain tRNAs, where it appears to play a role in ensuring rapid and accurate recognition of the corresponding mRNAs' codons. In the absence of queuosine modification, translation at Q-decoded codons slows down to the point that many proteins cannot fold properly.[7]

In animal experiments using "germ-free" mice, even the total absence of queuine in the diet is not lethal in the presence of an adequate supply of the dietary amino acid tyrosine. Withdrawal of tyrosine from the diet, however, causes rapid physical deterioration and death over a period of two weeks. Tyrosine is not typically an essential nutrient for animals provided dietary phenylalanine, suggesting that queuine depletion impairs the activity of phenylalanine hydroxylase.

Enzyme research

BH4 is a cofactor for the biopterin-dependent aromatic amino acid hydroxylase enzymes, which catalyze the conversion of phenylalanine to tyrosine, tyrosine to L-DOPA, and tryptophan to 5-HTP, oxidizing BH4 to dihydrobiopterin (BH2) in the process. BH2 must then be converted back to BH4 by the enzyme dihydropteridine reductase before it can be used again. Queuine depletion appears to impair this "recycling" process, resulting in a deficit of BH4 and an excess of BH2, which in turn impairs the activity of the aromatic amino acid hydroxylase enzymes.[8]

Because the aromatic amino acid hydroxylase enzymes are the rate-limiting steps in the body's biosynthesis of serotonin and dopamine (and subsequent metabolites including melatonin, norepinephrine, and adrenaline), queuine deficiency is under investigation as a potential cause of human diseases linked to a deficit of these neurotransmitters.[9]

References
  1. Farkas, Walter R. (1983). "Queuine, the Q-Containing tRNAs and the Enzymes Responsible for Their Formation". Nucleosides and Nucleotides. 2: 1–20. doi:10.1080/07328318308078845.
  2. Bjork, Glenn; Rasmusen, Torgny (1998). Modification and Editing of RNA. New York: ASM Press. p. 480. doi:10.1128/9781555818296.ch26. Whereas bacteria can synthesize the precursor preQ0, eukaryotic organisms are unable to make queuine and have to rely on the presence of the base in the diet. Queuine can therefore be considered a vitamin.
  3. Nishimura, Susumu; et al. (1983). Cohn, Waldo (ed.). Progress in Nucleic Acid Research and Molecular Biology. Vol. 28. New York: Academic Press, Inc. pp. 50–80. ISBN 0-12-540028-4.
  4. Zallot, Rémi; et al. (15 August 2014). "Plant, animal, and fungal micronutrient queuosine is salvaged by members of the DUF2419 protein family". ACS Chemical Biology. 9 (8): 1812–1825. doi:10.1021/cb500278k. PMC 4136680. PMID 24911101.
  5. Bjork, Glenn; Rasmusen, Torgny (1998). Modification and Editing of RNA. New York: ASM Press. p. 480. doi:10.1128/9781555818296.ch26. Whereas bacteria can synthesize the precursor preQ0, eukaryotic organisms are unable to make queuine and have to rely on the presence of the base in the diet. Queuine can therefore be considered a vitamin.
  6. Skolnick, Stephen; Greig, Nigel (1 March 2019). "Microbes and monoamines: Potential neuropsychiatric consequences of dysbiosis". Trends in Neurosciences. 42 (3): 151–163. doi:10.1016/j.tins.2018.12.005. PMID 30795845. S2CID 72335336. Retrieved 6 May 2020.
  7. Tuorto, Francesca; et al. (14 September 2018). "Queuosine-modified tRNAs confer nutritional control of protein translation". EMBO J. 37 (18): e99777. doi:10.15252/embj.201899777. PMC 6138434. PMID 30093495.
  8. Rakovich, Tatsiana; et al. (12 April 2011). "Queuosine deficiency in eukaryotes compromises tyrosine production through increased tetrahydrobiopterin oxidation". Journal of Biological Chemistry. 286 (22): 19354–19363. doi:10.1074/jbc.M111.219576. PMC 3103313. PMID 9016755.
  9. Pennisi, Elizabeth (2020). "Meet the Psychobiome". Science. 368 (6491): 570–573. doi:10.1126/science.368.6491.570. PMID 32381701. S2CID 218555010. Retrieved 23 November 2022.
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