Queuine () (Q) is a hypermodified

nucleobase Nucleotide bases (also nucleobases, nitrogenous bases) are nitrogen-containing biological compounds that form nucleosides, which, in turn, are components of nucleotides, with all of these monomers constituting the basic building blocks of nuc ...

found in the first (or

wobble Wobble or wobbles may refer to: * "Wobble" (song), a single by V.I.C. * "Wobble", a song by Flo Rida from his 2015 EP '' My House'' * ''Wobble'' (album), an album by Black Market Karma * Wobbles (equine disorder), a disorder of the nervous syst ...

) position of the

anticodon Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...

tRNA Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...

s specific for Asn, Asp, His, and Tyr, in most

eukaryotes The eukaryotes ( ) constitute the domain of Eukaryota or Eukarya, organisms whose cells have a membrane-bound nucleus. All animals, plants, fungi, seaweeds, and many unicellular organisms are eukaryotes. They constitute a major group of ...

and

prokaryotes A prokaryote (; less commonly spelled procaryote) is a single-celled organism whose cell lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Ancient Greek (), meaning 'before', and (), meaning 'nut' ...

. Because it is utilized by all eukaryotes but produced exclusively by bacteria, it is a putative vitamin. The

nucleoside Nucleosides are glycosylamines that can be thought of as nucleotides without a phosphate group. A nucleoside consists simply of a nucleobase (also termed a nitrogenous base) and a five-carbon sugar (ribose or 2'-deoxyribose) whereas a nucleotid ...

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 Guanine () (symbol G or Gua) is one of the four main nucleotide bases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine ( uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside ...

and other nucleobases, and "queuosine" by analogy to

guanosine Guanosine (symbol G or Guo) is a purine nucleoside comprising guanine attached to a ribose ( ribofuranose) ring via a β-N9- glycosidic bond. Guanosine can be phosphorylated to become guanosine monophosphate (GMP), cyclic guanosine monophosp ...

and other nucleosides.

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. 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 B vitamins are a class of water-soluble vitamins that play important roles in Cell (biology), cell metabolism and synthesis of red blood cells. They are a chemically diverse class of compounds. Dietary supplements containing all eight are referr ...

—many which are also produced primarily or exclusively by bacteria. The biosynthesis pathway for queuine shares a common enzymatic starting step with

folate Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

. 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 A vitamer () is any of the related forms in which some vitamin occurs. Each vitamer of a particular vitamin is a compound that performs the functions of that vitamin and prevents the symptoms of deficiency of the vitamin. Early research identifi ...

of queuine. As of 2019, human queuine requirements are not well understood, and the prevalence of queuine deficiency in humans is unknown. 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

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

s' codons. In the absence of queuosine modification, translation at Q-decoded codons slows down to the point that many proteins cannot fold properly. 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 -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is ...

. 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 Phenylalanine hydroxylase (PAH) () 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 clas ...

Enzyme research

BH₄ is a cofactor for the biopterin-dependent aromatic amino acid hydroxylase enzymes, which catalyze the conversion of

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the chemical formula, formula . It can be viewed as a benzyl group substituent, substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of ...

, tyrosine to

L-DOPA -DOPA, also known as -3,4-dihydroxyphenylalanine and used medically as levodopa, is made and used as part of the normal biology of some plants and animals, including humans. Humans, as well as a portion of the other animals that utilize -DO ...

, and

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromat ...

5-HTP 5-Hydroxytryptophan (5-HTP), used medically as oxitriptan, is a naturally occurring amino acid and chemical precursor as well as a metabolic intermediate in the biosynthesis of the neurotransmitter serotonin. 5-HTP can be manufactured and us ...

, oxidizing BH₄ to

dihydrobiopterin Dihydrobiopterin (BH2) is a pteridine compound produced in the synthesis of L-DOPA, dopamine, serotonin, norepinephrine and epinephrine. It is restored to the required cofactor tetrahydrobiopterin by dihydrobiopterin reductase. See also * Pt ...

(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. Because the aromatic amino acid hydroxylase enzymes are the rate-limiting steps in the body's biosynthesis of

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

and

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

(and subsequent metabolites including

melatonin Melatonin, an indoleamine, is a natural compound produced by various organisms, including bacteria and eukaryotes. Its discovery in 1958 by Aaron B. Lerner and colleagues stemmed from the isolation of a substance from the pineal gland of cow ...

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

, and

adrenaline Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

), queuine deficiency is under investigation as a potential cause of human diseases linked to a deficit of these neurotransmitters.

References

{{reflist

External links

* Human Metabolome Database
Queuine (HMDB01495)
Nucleobases Purines Cyclopentenes