Biopterin: Difference between revisions

| verifiedrevid = 444334205

| ImageFile = Biopterin.svg

| ImageSize = 230

| ImageAlt = Skeletal formula of biopterin

| ImageFile1 = Biopterin-3D-balls.png

| ImageSize1 = 230

| ImageAlt1 = Ball-and-stick model of the biopterin molecule (tautomer CID 445040)

| IUPACName= 2-Amino-6-(1,2-dihydroxypropyl)-1''H''-pteridin-4-one

| OtherNames=

|Section1={{Chembox Identifiers

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| CASNo_Ref = {{cascite|correct|??}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = E54CTM794Y

| PubChem = 445040

| SMILES = O=C2\N=C(/Nc1ncc(nc12)C(O)C(O)C)N

| MeSHName=Biopterin

|Section2={{Chembox Properties

| Formula=C₉H₁₁N₅O₃

| MolarMass=237.216 g/mol

| Appearance=

| Density=

| MeltingPt=

| BoilingPt=

| Solubility=

|Section3={{Chembox Hazards

| MainHazards=

| FlashPt=

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'''Biopterins''' are [[pterin]] derivatives which function as endogenous enzyme [[Cofactor (biochemistry)|cofactor]]s in many species of animals and in some bacteria and fungi. The prototypical compound of the class is '''biopterin''' (6-(1,2-dihydroxypropyl)-pterin), as shown in the infobox. Biopterins act as cofactors for [[Biopterin-dependent aromatic amino acid hydroxylase|aromatic amino acid hydroxylases]] (AAAH), which are involved in synthesizing a number of [[neurotransmitter]]s including [[dopamine]], [[norepinephrine]], [[epinepherine]], and [[serotonin]], along with several [[trace amine]]s. [[Nitric oxide]] synthesis also uses biopterin derivatives as cofactors. In humans, [[tetrahydrobiopterin]] (BH4) is the endogenous cofactor for AAAH enzymes.

As with pterins in general, biopterins exhibit [[tautomerism]]. In other words, there are a number of forms that readily interconvert, differing by the placement of hydrogen atoms. Depictions of the chemical structure may therefore vary among sources.<ref>{{cite journal |last1=Benkovic |first1=Stephen J. |last2=Sammons |first2=Douglas |last3=Armarego |first3=Wilfred L. F. |last4=Waring |first4=Paul |last5=Inners |first5=Ruth |title=Tautomeric nature of quinonoid 6,7-dimethyl-7,8-dihydro-6H-pterin in aqueous solution: a nitrogen-15 NMR study |journal=Journal of the American Chemical Society |date=June 1985 |volume=107 |issue=12 |pages=3706–3712 |doi=10.1021/ja00298a048}}</ref>

== Compounds ==

Biopterin compounds found in the animal body include [[tetrahydrobiopterin|BH4]], the [[free radical]]<ref>{{cite journal |doi=10.1074/jbc.M302227200 |pmid=12692136 |title=Interactions of Peroxynitrite, Tetrahydrobiopterin, Ascorbic Acid, and Thiols: Implications For Uncoupling Endothelial Nitric-Oxide Synthase |journal=Journal of Biological Chemistry |volume=278 |issue=25 |pages=22546–54 |year=2003 |last1=Kuzkaya |first1=N. |last2=Weissmann |first2=N. |last3=Harrison |first3=D. G. |last4=Dikalov |first4=S. |doi-access=free }}</ref> BH3•, and the semi-oxidized form [[dihydrobiopterin|BH2]]. The fully oxidized form, i.e. "biopterin" proper, has little biological significance.

Bacteria produce several unique [[glycoside]]s of biopterin (and of other pterins as well), using a specific BPt glucosyltransferase. They may have a function in [[ultraviolet|UV]] protection.<ref>{{cite journal |last1=Feirer |first1=Nathan |last2=Fuqua |first2=Clay |title=Pterin function in bacteria |journal=Pteridines |date=1 May 2017 |volume=28 |issue=1 |pages=23–36 |doi=10.1515/pterid-2016-0012|s2cid=91132135 |url=http://iu.tind.io/record/732/files/0448_Pterin-function-in-bacteria.pdf }}</ref>

== Biosynthesis ==

BH4 is the principal active cofactor. BH4 synthesis occurs through two principal pathways; the de novo pathway involves three enzymatic steps and proceeds from [[Guanosine triphosphate|GTP]], while the salvage pathway converts [[sepiapterin]] to BH4 using [[dihydrofolate reductase]].<ref>{{Cite journal

| pmid = 6572916

| pmc = 393638

| year = 1983

| last1 = Nichol

| first1 = C. A.

| title = Biosynthesis of tetrahydrobiopterin by de novo and salvage pathways in adrenal medulla extracts, mammalian cell cultures, and rat brain in vivo

| journal = Proceedings of the National Academy of Sciences of the United States of America

| volume = 80

| issue = 6

| pages = 1546–50

| last2 = Lee

| first2 = C. L.

| last3 = Edelstein

| first3 = M. P.

| last4 = Chao

| first4 = J. Y.

| last5 = Duch

| first5 = D. S.

| doi=10.1073/pnas.80.6.1546

| bibcode = 1983PNAS...80.1546N

| doi-access = free

}}</ref> In addition, BH2 is recycled to BH4 by [[dihydrobiopterin reductase]].

In the ''de novo'' pathway, GTP is converted to 7,8-dihydro[[neopterin]] triphosphate by [[GTP cyclohydrolase I]] (GTPCH-1, ''FolE''), which expands the imidazole ring in GTP by one carbon. The intermediate is converted to 6-pyruvoyl-5,6,7,8-tetrahydropterin by [[6-pyruvoyltetrahydropterin synthase]], which removes the phosphate and produces the diketone (pyruvoyl) substituent. The final stage is mediated by [[sepiapterin reductase]].<ref>{{cite journal|doi=10.1042/BJ20110293|title=Tetrahydrobiopterin: Biochemistry and pathophysiology |year=2011 |last1=Werner |first1=Ernst R. |last2=Blau |first2=Nenad |last3=Thöny |first3=Beat |journal=Biochemical Journal |volume=438 |issue=3 |pages=397–414 |pmid=21867484 }}</ref>

[[File:DihydroneopterinTriphosphate.png|thumb|center|390px|step in biosynthesis of dihydroneopterin from GTP.]]

== Biopterin disorders ==

{{main|Tetrahydrobiopterin deficiency|Tetrahydrobiopterin-deficient hyperphenylalaninemia}}

A number of disorders of biopterin regulation exist.

Single-gene defects affecting the gene [[GCH1]] block the first step in biopterin synthesis, and lead to [[dopamine-responsive dystonia]], also known as Segawa's syndrome. This is due to the role of BH4 in synthesising neurotransmitters, including Dopamine, and is treated with supplementation with [[levodopa]], which does not require BH4 for conversion to dopamine. GCH1 defects are autosomal dominant, meaning that only one defective gene copy is required for the condition to occur. Mouse gene knockout models that block biopterin synthesis completely die shortly after birth due to their inability to produce catecholamines and neurotransmitters.<ref>{{Cite journal

| pmid = 12734191

| year = 2003

| last1 = Elzaouk

| first1 = L

| title = Dwarfism and low insulin-like growth factor-1 due to dopamine depletion in Pts-/- mice rescued by feeding neurotransmitter precursors and H4-biopterin

| journal = Journal of Biological Chemistry

| volume = 278

| issue = 30

| pages = 28303–11

| last2 = Leimbacher

| first2 = W

| last3 = Turri

| first3 = M

| last4 = Ledermann

| first4 = B

| last5 = Burki

| first5 = K

| last6 = Blau

| first6 = N

| last7 = Thony

| first7 = B

| doi = 10.1074/jbc.M303986200

| doi-access = free

}}</ref>

Biopterin synthesis disorders are also a cause of hyperphenylalaninemia; phenylalanine metabolism requires BH4 as a cofactor.<ref>{{cite web |url=http://www.uic.edu/classes/phar/phar332/Clinical_Cases/aa%20metab%20cases/PKU%20Cases/bioh4.htm |title=Tetrahydrobiopterin |accessdate=2007-06-07 |url-status=dead |archiveurl=https://web.archive.org/web/20070629030636/http://www.uic.edu/classes/phar/phar332/Clinical_Cases/aa%20metab%20cases/PKU%20Cases/bioh4.htm |archivedate=2007-06-29 }}</ref>

In psychiatry, imbalances of biopterin concentrations have been hypothesized to be linked to mood disorders, particularly depression.<ref> Cavaleri et al. Blood concentrations of neopterin and biopterin in subjects with depression: A systematic review and meta-analysis ''Progress in Neuro-Psychopharmacology and Biological Psychiatry'' 2022. http://dx.doi.org/10.1016/j.pnpbp.2022.110633 </ref>

{{Reflist}}

==External links==

*[http://adc.bmj.com/content/61/2/130.full.pdf Neurological aspects of biopterin metabolism]

WiseGeek. (2012). What is biopterin?. Retrieved from http://www.wisegeek.com/what-is-biopterin.htm