Pterin

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Pterin
Pterin - Pterin.svg
Names
IUPAC names
2-Aminopteridin-4(3H)-one
(one of many tautomers; see text)
Other names
Pteridoxamine
Pterine
4-Oxopterin
2-Amino-4-pteridone
2-Amino-4-hydroxypteridine
2-Amino-4-oxopteridine
2-aminopteridin-4-ol
2-Amino-4-pteridinol
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.017.091 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
  • InChI=1S/C6H5N5O/c7-6-10-4-3(5(12)11-6)8-1-2-9-4/h1-2H,(H3,7,9,10,11,12) Yes check.svgY
    Key: HNXQXTQTPAJEJL-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C6H5N5O/c7-6-10-4-3(5(12)11-6)8-1-2-9-4/h1-2H,(H3,7,9,10,11,12)
    Key: HNXQXTQTPAJEJL-UHFFFAOYAD
  • O=C2\N=C(/Nc1nccnc12)N
Properties
C6H5N5O
Molar mass 163.137
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 ?)

Pterin is a heterocyclic compound composed of a pteridine ring system, with a "keto group" (a lactam) and an amino group on positions 4 and 2 respectively. It is structurally related to the parent bicyclic heterocycle called pteridine. Pterins, as a group, are compounds related to pterin with additional substituents. Pterin itself is of no biological significance.

Contents

Pterins were first discovered in the pigments of butterfly wings [1] (hence the origin of their name, from the Greek pteron (πτερόν), [2] wing) and perform many roles in coloration in the biological world.

Chemistry

Pterins exhibit a wide range of tautomerism in water, beyond what is assumed by just keto-enol tautomerism. For the unsubstituted pterin, at least five tautomers are commonly cited. [3] For 6-methylpterin, seven tautomers are theoretically predicted to be important in solution. [4]

The pteridine ring system contains four nitrogen atoms, reducing its aromaticity to the point that it can be attacked by nucleophile. Pterins can take three oxidation states on the ring system: the unprefixed oxidized form, the 7,8-dihydro semi-reduced form (among other, less stable tautomers), and finally the 5,6,7,8-tetrahydro fully-reduced form. The latter two are more common in biological systems. [5]

Biosynthesis

Pterin rings are either salvaged from existing ones or produced de novo in living organisms. The ring comes from rearrangement of guanosine in bacteria [6] and humans. [7]

Biosynthesis of tetrahydrobiopterin (BH4) and derivatives. Sepiapterin is a yellow pigment. Biosynthesis and recycling of BH4.jpg
Biosynthesis of tetrahydrobiopterin (BH4) and derivatives. Sepiapterin is a yellow pigment.

Pterin cofactors

Pterin derivatives are common cofactors in all domains of life.

Folates

One important family of pterin derivatives are folates. Folates are pterins that contain p-aminobenzoic acid connected to the methyl group at position 6 of the pteridine ring system (known as pteroic acid) conjugated with one or more L-glutamates. They participate in numerous biological group transfer reactions. Folate-dependent biosynthetic reactions include the transfer of methyl groups from 5-methyltetrahydrofolate to homocysteine to form L-methionine, and the transfer of formyl groups from 10-formyltetrahydrofolate to L-methionine to form N-formylmethionine in initiator tRNAs. Folates are also essential for the biosynthesis of purines and one pyrimidine.

Substituted pteridines are intermediates in the biosynthesis of dihydrofolic acid in many microorganisms. [9] The enzyme dihydropteroate synthetase converts pteridine and 4-aminobenzoic acid to dihydrofolic acid in the presence of glutamate. The enzyme dihydropteroate synthetase is inhibited by sulfonamide antibiotics.

Molybdopterin

Moco biosynthetic pathway in bacteria and humans. The human enzymes are indicated in parentheses. Moco Biosynthetic Pathway.pdf
Moco biosynthetic pathway in bacteria and humans. The human enzymes are indicated in parentheses.

Molybdopterin is a cofactor found in virtually all molybdenum and tungsten-containing proteins. [6] It binds molybdenum to yield redox cofactors involved in biological hydroxylations, reduction of nitrate, and respiratory oxidation. [11]

Molybdopterin biosynthesis does not use the conventional GTPCH-1 pathway. It occurs in four steps: [10]

  1. the radical-mediated cyclization of nucleotide, guanosine 5′-triphosphate (GTP), to (8S)‑3′,8‐cyclo‑7,8‑dihydroguanosine 5′-triphosphate (3′,8‑cH2GTP),
  2. the formation of cyclic pyranopterin monophosphate (cPMP) from the 3′,8‑cH2GTP,
  3. the conversion of cPMP into molybdopterin (MPT),
  4. the insertion of molybdate into MPT to form Moco (molybdenum cofactor).

Tetrahydrobiopterin

Tetrahydrobiopterin, the major unconjugated pterin in vertebrates, is involved in three families of enzymes that effect hydroxylation. The aromatic amino acid hydroxylases include phenylalanine hydroxylase, tyrosine hydroxylase, and tryptophan hydroxylases. They are involved in the synthesis of neurotransmitters catecholamine and serotonin. Tetrahydrobiopterin is also required for the functioning of alkylglycerol monooxygenase, whereby monoalkylglycerols are broken down to glycerol and an aldehyde. In the synthesis of nitric oxide the pterin-dependent nitric oxide synthase converts arginine to its N-hydroxy derivative, which in turn releases nitric oxide. [12]

Other pterins

Cycle for methanogenesis, showing intermediates. Methanogenesis cycle.png
Cycle for methanogenesis, showing intermediates.

Tetrahydromethanopterin is a cofactor in methanogenesis, which is a metabolism adopted by many organisms, as a form of anaerobic respiration. [13] It carries the C1 substrate in the course of the formation or production of methane. It is structurally similar to folate.

Pterin pigments

The wings of the orange tip butterfly are colored by orange pterin-containing pigments. Orange tip (Anthocharis cardamines) male.jpg
The wings of the orange tip butterfly are colored by orange pterin-containing pigments.

Cyanopterin is a glycosylated derivative of pteridine, having an unknown function in cyanobacteria. [15]


See also

Related Research Articles

<span class="mw-page-title-main">Flavin group</span> Group of chemical compounds

Flavins refers generally to the class of organic compounds containing the tricyclic heterocycle isoalloxazine or its isomer alloxazine, and derivatives thereof. The biochemical source of flavin is the yellow B vitamin riboflavin. The flavin moiety is often attached with an adenosine diphosphate to form flavin adenine dinucleotide (FAD), and, in other circumstances, is found as flavin mononucleotide, a phosphorylated form of riboflavin. It is in one or the other of these forms that flavin is present as a prosthetic group in flavoproteins. Despite the similar names, flavins are chemically and biologically distinct from the flavanoids, and the flavonols.

<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.

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

Tetrahydrobiopterin (BH4, THB), also known as sapropterin (INN), is a cofactor of the three aromatic amino acid hydroxylase enzymes, used in the degradation of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotonin (5-hydroxytryptamine, 5-HT), melatonin, dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and is a cofactor for the production of nitric oxide (NO) by the nitric oxide synthases. Chemically, its structure is that of a (dihydropteridine reductase) reduced pteridine derivative (quinonoid dihydrobiopterin).

<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.

<span class="mw-page-title-main">GTP cyclohydrolase I</span>

GTP cyclohydrolase I (GTPCH) (EC 3.5.4.16) is a member of the GTP cyclohydrolase family of enzymes. GTPCH is part of the folate and biopterin biosynthesis pathways. It is responsible for the hydrolysis of guanosine triphosphate (GTP) to form 7,8-dihydroneopterin triphosphate (7,8-DHNP-3'-TP, 7,8-NH2-3'-TP).

<span class="mw-page-title-main">Molybdopterin</span> Heterocyclic ligand that can complex molybdenum to form a Mo-cofactor

Molybdopterins are a class of cofactors found in most molybdenum-containing and all tungsten-containing enzymes. Synonyms for molybdopterin are: MPT and pyranopterin-dithiolate. The nomenclature for this biomolecule can be confusing: Molybdopterin itself contains no molybdenum; rather, this is the name of the ligand that will bind the active metal. After molybdopterin is eventually complexed with molybdenum, the complete ligand is usually called molybdenum cofactor.

<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 monoamine 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">Dihydropteroate</span> Chemical compound

Dihydropteroate is an important intermediate in folate biosynthesis. It is a pterin created from para-aminobenzoic acid (PABA) by the enzyme dihydropteroate synthase.

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

Biopterins are pterin derivatives which function as endogenous enzyme cofactors in many species of animals and in some bacteria and fungi. The prototypical compound of the class is biopterin, as shown in the infobox. Biopterins act as cofactors for aromatic amino acid hydroxylases (AAAH), which are involved in synthesizing a number of neurotransmitters including dopamine, norepinephrine, epinepherine, and serotonin, along with several trace amines. Nitric oxide synthesis also uses biopterin derivatives as cofactors. In humans, tetrahydrobiopterin (BH4) is the endogenous cofactor for AAAH enzymes.

In enzymology, an anthranilate 3-monooxygenase (EC 1.14.16.3) is an enzyme that catalyzes the chemical reaction

Alkylglycerol monooxygenase (AGMO) is an enzyme that catalyzes the hydroxylation of alkylglycerols, a specific subclass of ether lipids. This enzyme was first described in 1964 as a pteridine-dependent ether lipid cleaving enzyme. In 2010 finally, the gene coding for alkylglycerol monooxygenase was discovered as transmembrane protein 195 (TMEM195) on chromosome 7. In analogy to the enzymes phenylalanine hydroxylase, tyrosine hydroxylase, tryptophan hydroxylase and nitric oxide synthase, alkylglycerol monooxygenase critically depends on the cofactor tetrahydrobiopterin and iron.

<span class="mw-page-title-main">Dihydrofolate synthase</span> Class of enzymes

In enzymology, a dihydrofolate synthase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">6-Pyruvoyltetrahydropterin synthase</span> Class of enzymes

The enzyme 6-pyruvoyltetrahydropterin synthase catalyzes the following chemical reaction:

<span class="mw-page-title-main">PCBD1</span> Protein-coding gene in the species Homo sapiens

Pterin-4-alpha-carbinolamine dehydratase is an enzyme that in humans is encoded by the PCBD1 gene.

<span class="mw-page-title-main">MOCS2</span> Protein-coding gene in the species Homo sapiens

Molybdenum cofactor synthesis protein 2A and molybdenum cofactor synthesis protein 2B are a pair of proteins that in humans are encoded from the same MOCS2 gene. These two proteins dimerize to form molybdopterin synthase.

Molybdopterin synthase (EC 2.8.1.12, MPT synthase) is an enzyme required to synthesize molybdopterin (MPT) from precursor Z (now known as cyclic pyranopterin monophosphate). Molydopterin is subsequently complexed with molybdenum to form molybdenum cofactor (MoCo). MPT synthase catalyses the following chemical reaction:

Molybdenum cofactor cytidylyltransferase is an enzyme with systematic name CTP:molybdenum cofactor cytidylyltransferase. This enzyme catalyses the following chemical reaction:

<span class="mw-page-title-main">Aldehyde ferredoxin oxidoreductase</span>

In enzymology, an aldehyde ferredoxin oxidoreductase (EC 1.2.7.5) is an enzyme that catalyzes the chemical reaction

Catecholamines up (Catsup) is a dopamine regulatory membrane protein that functions as a zinc ion transmembrane transporter (orthologous to ZIP7), and a negative regulator of rate-limiting enzymes involved in dopamine synthesis and transport: Tyrosine hydroxylase (TH), GTP Cyclohydrolase I (GTPCH), and Vesicular Monoamine Transporter (VMAT) in Drosophila melanogaster.

References

  1. ↑ Wijnen B, Leertouwer HL, Stavenga DG (December 2007). "Colors and pterin pigmentation of pierid butterfly wings" (PDF). Journal of Insect Physiology. 53 (12): 1206–1217. doi:10.1016/j.jinsphys.2007.06.016. PMID   17669418. S2CID   13787442.
  2. ↑ πτερόν . Liddell, Henry George ; Scott, Robert ; A Greek–English Lexicon at the Perseus Project
  3. ↑ Spyrakis F, Dellafiora L, Da C, Kellogg GE, Cozzini P (2013). "Correct protonation states and relevant waters = better computational simulations?". Current Pharmaceutical Design. 19 (23): 4291–4309. doi:10.2174/1381612811319230011. PMID   23170888.
  4. ↑ Nekkanti S, Martin CB (1 March 2015). "Theoretical study on the relative energies of cationic pterin tautomers". Pteridines. 26 (1): 13–22. doi: 10.1515/pterid-2014-0011 .
  5. ↑ Basu P, Burgmayer SJ (May 2011). "Pterin chemistry and its relationship to the molybdenum cofactor". Coordination Chemistry Reviews. 255 (9–10): 1016–1038. doi:10.1016/j.ccr.2011.02.010. PMC   3098623 . PMID   21607119.
  6. 1 2 Feirer N, Fuqua C (1 May 2017). "Pterin function in bacteria" (PDF). Pteridines. 28 (1): 23–36. doi:10.1515/pterid-2016-0012. S2CID   91132135.
  7. ↑ Werner ER, Blau N, Thöny B (September 2011). "Tetrahydrobiopterin: biochemistry and pathophysiology". The Biochemical Journal. 438 (3): 397–414. doi:10.1042/BJ20110293. PMID   21867484.
  8. ↑ Jung-Klawitter S, Kuseyri Hübschmann O (August 2019). "Analysis of Catecholamines and Pterins in Inborn Errors of Monoamine Neurotransmitter Metabolism-From Past to Future". Cells. 8 (8): 867. doi: 10.3390/cells8080867 . PMC   6721669 . PMID   31405045.
  9. ↑ Voet D, Voet JG (2004). Biochemistry (3rd ed.). John Wiley & Sons. ISBN   0-471-39223-5.
  10. 1 2 Schwarz G, Mendel RR (2006). "Molybdenum cofactor biosynthesis and molybdenum enzymes". Annual Review of Plant Biology. 57: 623–647. doi:10.1146/annurev.arplant.57.032905.105437. PMID   16669776.
  11. ↑ Schwarz G, Mendel RR, Ribbe MW (August 2009). "Molybdenum cofactors, enzymes and pathways". Nature. 460 (7257): 839–847. Bibcode:2009Natur.460..839S. doi:10.1038/nature08302. PMID   19675644. S2CID   205217953.
  12. ↑ Werner ER (2013-01-01). "Three classes of tetrahydrobiopterin-dependent enzymes". Pteridines. 24 (1): 7–11. doi: 10.1515/pterid-2013-0003 . ISSN   2195-4720. S2CID   87712042.
  13. ↑ Thauer RK (September 1998). "Biochemistry of methanogenesis: a tribute to Marjory Stephenson. 1998 Marjory Stephenson Prize Lecture". Microbiology. 144 (9): 2377–2406. doi: 10.1099/00221287-144-9-2377 . PMID   9782487.
  14. ↑ Wijnen B, Leertouwer HL, Stavenga DG (December 2007). "Colors and pterin pigmentation of pierid butterfly wings" (PDF). Journal of Insect Physiology. 53 (12): 1206–1217. doi:10.1016/j.jinsphys.2007.06.016. PMID   17669418. S2CID   13787442.
  15. ↑ Lee HW, Oh CH, Geyer A, Pfleiderer W, Park YS (January 1999). "Characterization of a novel unconjugated pteridine glycoside, cyanopterin, in Synechocystis sp. PCC 6803". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1410 (1): 61–70. doi: 10.1016/S0005-2728(98)00175-3 . PMID   10076015.
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