Biopterin

Compounds

Biopterin compounds found in the animal body include BH4, the free radical BH3•, and the semi-oxidized form BH2. The fully oxidized form, i.e. "biopterin" proper, has little biological significance.

Bacteria produce several unique glycosides 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.{{Cite journal | doi-access = free

In the de novo pathway, GTP is converted to 7,8-dihydroneopterin 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.

Biopterin disorders

Main article: 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.{{Cite journal | doi-access = free

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.

References

References

1. (June 1985). "Tautomeric nature of quinonoid 6,7-dimethyl-7,8-dihydro-6H-pterin in aqueous solution: a nitrogen-15 NMR study". Journal of the American Chemical Society.
2. (2003). "Interactions of Peroxynitrite, Tetrahydrobiopterin, Ascorbic Acid, and Thiols: Implications For Uncoupling Endothelial Nitric-Oxide Synthase". Journal of Biological Chemistry.
3. (1 May 2017). "Pterin function in bacteria". Pteridines.
4. (2011). "Tetrahydrobiopterin: Biochemistry and pathophysiology". Biochemical Journal.
5. "Tetrahydrobiopterin".
6. 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