Biopterins are

pterin 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. Pter ...

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 (6-(1,2-dihydroxypropyl)-pterin), as shown in the infobox. Biopterins act as cofactors for aromatic amino acid hydroxylases (AAAH), which are involved in synthesizing a number of

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

s including

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 ...

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 ...

, epinepherine, and

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, ...

, along with several

trace amine Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to ...

Nitric oxide Nitric oxide (nitrogen oxide, nitrogen monooxide, or nitrogen monoxide) is a colorless gas with the formula . It is one of the principal oxides of nitrogen. Nitric oxide is a free radical: it has an unpaired electron, which is sometimes den ...

synthesis also uses biopterin derivatives as cofactors. In humans,

tetrahydrobiopterin Tetrahydrobiopterin (BH4, THB), also known as sapropterin ( INN), is a cofactor of the three aromatic amino acid hydroxylase enzymes, used in the metabolism of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotoni ...

(BH4) is the endogenous cofactor for AAAH enzymes. As with pterins in general, biopterins exhibit

tautomerism In chemistry, tautomers () are structural isomers (constitutional isomers) of chemical compounds that readily interconvert. The chemical reaction interconverting the two is called tautomerization. This conversion commonly results from the reloca ...

. 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.

Compounds

Biopterin compounds found in the animal body include

BH4 Tetrahydrobiopterin (BH4, THB), also known as sapropterin (INN), is a cofactor of the three aromatic amino acid hydroxylase enzymes, used in the metabolism of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotonin ...

, the

free radical A daughter category of ''Ageing'', this category deals only with the biological aspects of ageing. Ageing Biogerontology Biological processes Causes of death Cellular processes Gerontology Life extension Metabolic disorders Metabolism ...

BH3•, and the semi-oxidized form BH2. The fully oxidized form, i.e. "biopterin" proper, has little biological significance. Bacteria produce several unique

glycoside In chemistry, a glycoside is a molecule in which a sugar is bound to another functional group via a glycosidic bond. Glycosides play numerous important roles in living organisms. Many plants store chemicals in the form of inactive glycosides. ...

s of biopterin (and of other pterins as well), using a specific BPt glucosyltransferase. They may have a function in UV protection.

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 GTP, while the salvage pathway converts sepiapterin to BH4 using

dihydrofolate reductase Dihydrofolate reductase, or DHFR, is an enzyme that reduces dihydrofolic acid to tetrahydrofolic acid, using NADPH as an electron donor, which can be converted to the kinds of tetrahydrofolate cofactors used in one-carbon transfer chemistry. ...

. 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 GTP cyclohydrolase I (GTPCH) () 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-dihydro ...

(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. DihydroneopterinTriphosphate

Biopterin disorders

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 Dopamine-responsive dystonia (DRD) also known as Segawa syndrome (SS), is a genetic movement disorder which usually manifests itself during early childhood at around ages 5–8 years (variable start age). Characteristic symptoms are increased m ...

, 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 Levodopa, also known as L-DOPA and sold under many brand names, is a dopaminergic medication which is used in the treatment of Parkinson's disease (PD) and certain other conditions like dopamine-responsive dystonia and restless legs syndrome. ...

, 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. Biopterin synthesis disorders are also a cause of hyperphenylalaninemia; phenylalanine metabolism requires BH4 as a cofactor. In psychiatry, imbalances of biopterin concentrations have been hypothesized to be linked to mood disorders, particularly depression. 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

References

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External links

Neurological aspects of biopterin metabolism
WiseGeek. (2012). What is biopterin?. Retrieved from http://www.wisegeek.com/what-is-biopterin.htm Coenzymes Pteridines