Queuine

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Queuine
Queuine.svg
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
PubChem CID
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 X mark.svgN
    Key: WYROLENTHWJFLR-ACLDMZEESA-N X mark.svgN
  • 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).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

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]

Related Research Articles

<span class="mw-page-title-main">Phenylketonuria</span> Amino acid metabolic disorder

Phenylketonuria (PKU) is an inborn error of metabolism that results in decreased metabolism of the amino acid phenylalanine. Untreated PKU can lead to intellectual disability, seizures, behavioral problems, and mental disorders. It may also result in a musty smell and lighter skin. A baby born to a mother who has poorly treated PKU may have heart problems, a small head, and low birth weight.

<span class="mw-page-title-main">Tyrosine</span> Amino acid

L-Tyrosine or tyrosine or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Greek tyrós, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese. It is called tyrosyl when referred to as a functional group or side chain. While tyrosine is generally classified as a hydrophobic amino acid, it is more hydrophilic than phenylalanine. It is encoded by the codons UAC and UAU in messenger RNA.

<span class="mw-page-title-main">Phenylalanine</span> Type of α-amino acid

Phenylalanine is an essential α-amino acid with the formula C
9H
11NO
2. It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino acid is classified as neutral, and nonpolar because of the inert and hydrophobic nature of the benzyl side chain. The L-isomer is used to biochemically form proteins coded for by DNA. Phenylalanine is a precursor for tyrosine, the monoamine neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline), and the skin pigment melanin. It is encoded by the codons UUU and UUC.

<span class="mw-page-title-main">Catecholamine</span> Class of chemical compounds

A catecholamine is a monoamine neurotransmitter, an organic compound that has a catechol and a side-chain amine.

<span class="mw-page-title-main">Phenylalanine hydroxylase</span> Mammalian protein found in Homo sapiens

Phenylalanine hydroxylase. (PAH) (EC 1.14.16.1) is an enzyme that catalyzes the hydroxylation of the aromatic side-chain of phenylalanine to generate tyrosine. PAH is one of three members of the biopterin-dependent aromatic amino acid hydroxylases, a class of monooxygenase that uses tetrahydrobiopterin (BH4, a pteridine cofactor) and a non-heme iron for catalysis. During the reaction, molecular oxygen is heterolytically cleaved with sequential incorporation of one oxygen atom into BH4 and phenylalanine substrate. In humans, mutations in its encoding gene, PAH, can lead to the metabolic disorder phenylketonuria.

In chemistry, hydroxylation can refer to:

<span class="mw-page-title-main">Transfer RNA</span> RNA that facilitates the addition of amino acids to a new protein

Transfer RNA is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length, that serves as the physical link between the mRNA and the amino acid sequence of proteins. tRNAs genes from Bacteria are typically shorter than tRNAs from Archaea and eukaryotes. The mature tRNA follows an opposite pattern with tRNAs from Bacteria being usually longer than tRNAs from Archaea, with eukaryotes exhibiting the shortest mature tRNAs. Transfer RNA (tRNA) does this by carrying an amino acid to the protein synthesizing machinery of a cell called the ribosome. Complementation of a 3-nucleotide codon in a messenger RNA (mRNA) by a 3-nucleotide anticodon of the tRNA results in protein synthesis based on the mRNA code. As such, tRNAs are a necessary component of translation, the biological synthesis of new proteins in accordance with the genetic code.

Shikimic acid, more commonly known as its anionic form shikimate, is a cyclohexene, a cyclitol and a cyclohexanecarboxylic acid. It is an important biochemical metabolite in plants and microorganisms. Its name comes from the Japanese flower shikimi, from which it was first isolated in 1885 by Johan Fredrik Eykman. The elucidation of its structure was made nearly 50 years later.

<span class="mw-page-title-main">Tetrahydrobiopterin deficiency</span> Medical condition

Tetrahydrobiopterin deficiency (THBD, BH4D) is a rare metabolic disorder that increases the blood levels of phenylalanine. Phenylalanine is an amino acid obtained normally through the diet, but can be harmful if excess levels build up, causing intellectual disability and other serious health problems. In healthy individuals, it is metabolised (hydroxylated) into tyrosine, another amino acid, by phenylalanine hydroxylase. However, this enzyme requires tetrahydrobiopterin as a cofactor and thus its deficiency slows phenylalanine metabolism.

<i>N</i>-Formylmethionine Chemical compound

N-Formylmethionine is a derivative of the amino acid methionine in which a formyl group has been added to the amino group. It is specifically used for initiation of protein synthesis from bacterial and organellar genes, and may be removed post-translationally.

<span class="mw-page-title-main">Tyrosine hydroxylase</span> Enzyme found in Homo sapiens that converts l-tyrosine to l-dopa, the precursor of cathecolamines

Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA). It does so using molecular oxygen (O2), as well as iron (Fe2+) and tetrahydrobiopterin as cofactors. L-DOPA is a precursor for dopamine, which, in turn, is a precursor for the important neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline). Tyrosine hydroxylase catalyzes the rate limiting step in this synthesis of catecholamines. In humans, tyrosine hydroxylase is encoded by the TH gene, and the enzyme is present in the central nervous system (CNS), peripheral sympathetic neurons and the adrenal medulla. Tyrosine hydroxylase, phenylalanine hydroxylase and tryptophan hydroxylase together make up the family of aromatic amino acid hydroxylases (AAAHs).

<span class="mw-page-title-main">Tryptophan hydroxylase</span> Class of enzymes

Tryptophan hydroxylase (TPH) is an enzyme (EC 1.14.16.4) involved in the synthesis of the neurotransmitter serotonin. Tyrosine hydroxylase, phenylalanine hydroxylase, and tryptophan hydroxylase together constitute the family of biopterin-dependent aromatic amino acid hydroxylases. TPH catalyzes the following chemical reaction

<span class="mw-page-title-main">Aromatic amino acid</span> Amino acid having an aromatic ring

An aromatic amino acid is an amino acid that includes an aromatic ring.

<span class="mw-page-title-main">PreQ1 riboswitch</span>

The PreQ1-I riboswitch is a cis-acting element identified in bacteria which regulates expression of genes involved in biosynthesis of the nucleoside queuosine (Q) from GTP. PreQ1 (pre-queuosine1) is an intermediate in the queuosine pathway, and preQ1 riboswitch, as a type of riboswitch, is an RNA element that binds preQ1. The preQ1 riboswitch is distinguished by its unusually small aptamer, compared to other riboswitches. Its atomic-resolution three-dimensional structure has been determined, with the PDB ID 2L1V.

<span class="mw-page-title-main">Phenylalanine—tRNA ligase</span>

In enzymology, a phenylalanine—tRNA ligase is an enzyme that catalyzes the chemical reaction

In enzymology, glutamate-prephenate aminotransferase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Queuosine</span> Chemical compound

Queuosine is a modified nucleoside that is present in certain tRNAs in bacteria and eukaryotes. It contains the nucleobase queuine. Originally identified in E. coli, queuosine was found to occupy the first anticodon position of tRNAs for histidine, aspartic acid, asparagine and tyrosine. The first anticodon position pairs with the third "wobble" position in codons, and queuosine improves accuracy of translation compared to guanosine. Synthesis of queuosine begins with GTP. In bacteria, three structurally unrelated classes of riboswitch are known to regulate genes that are involved in the synthesis or transport of pre-queuosine1, a precursor to queuosine: PreQ1-I riboswitches, PreQ1-II riboswitches and PreQ1-III riboswitches.

<span class="mw-page-title-main">C9orf64</span> Protein-coding gene in the species Homo sapiens

C9orf64 is a gene located on chromosome 9, that in humans encodes the protein queuosine salvage protein. The function and biological process of the queuosine salvage protein is a queuosine-nucleotide N-glycosylase/hydrolase (QNG1) that releases queuine from Q-5'-monophosphate, and this activity is required for the salvage of queuine from exogenous Queuosine by S. pombe and HeLa cells. Some evidence from orthologs indicates it may be involved in tRNA processing and recycling. The most common mRNA contains 4 coding exons, and it has 2 additional alternatively spliced exons. C9orf64 has been found in 5 different splice variants.

<span class="mw-page-title-main">Biopterin-dependent aromatic amino acid hydroxylase</span>

Biopterin-dependent aromatic amino acid hydroxylases (AAAH) are a family of aromatic amino acid hydroxylase enzymes which includes phenylalanine 4-hydroxylase, tyrosine 3-hydroxylase, and tryptophan 5-hydroxylase. These enzymes primarily hydroxylate the amino acids L-phenylalanine, L-tyrosine, and L-tryptophan, respectively.

<span class="mw-page-title-main">Wybutosine</span> Chemical compound

In biochemistry, wybutosine (yW) is a heavily modified nucleoside of phenylalanine transfer RNA that stabilizes interactions between the codons and anti-codons during protein synthesis. Ensuring accurate synthesis of protein is essential in maintaining health as defects in tRNA modifications are able to cause disease. In eukaryotic organisms, it is found only in position 37, 3'-adjacent to the anticodon, of phenylalanine tRNA. Wybutosine enables correct translation through the stabilization of the codon-anticodon base pairing during the decoding process.

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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