Enzymes
| UniProtKB help_outline | 88 proteins |
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- Name help_outline L-sepiapterin Identifier CHEBI:194527 Charge 0 Formula C9H11N5O3 InChIKeyhelp_outline VPVOXUSPXFPWBN-VKHMYHEASA-N SMILEShelp_outline C12=C(N=C(C([C@H](C)O)=O)CN1)C(NC(=N2)N)=O 2D coordinates Mol file for the small molecule Search links Involved in 6 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline a dicarboxylate Identifier CHEBI:28965 Charge -2 Formula C2O4R SMILEShelp_outline [O-]C(=O)[*]C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 1,131 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:76079 | RHEA:76080 | RHEA:76081 | RHEA:76082 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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Organic anion transporters, OAT1 and OAT3, are crucial biopterin transporters involved in bodily distribution of tetrahydrobiopterin and exclusion of its excess.
Ohashi A., Mamada K., Harada T., Naito M., Takahashi T., Aizawa S., Hasegawa H.
Tetrahydrobiopterin (BH<sub>4</sub>) is a common coenzyme of phenylalanine-, tyrosine-, and tryptophan hydroxylases, alkylglycerol monooxygenase, and NO synthases (NOS). Synthetic BH<sub>4</sub> is used medicinally for BH<sub>4</sub>-responsive phenylketonuria and inherited BH<sub>4</sub> deficien ... >> More
Tetrahydrobiopterin (BH<sub>4</sub>) is a common coenzyme of phenylalanine-, tyrosine-, and tryptophan hydroxylases, alkylglycerol monooxygenase, and NO synthases (NOS). Synthetic BH<sub>4</sub> is used medicinally for BH<sub>4</sub>-responsive phenylketonuria and inherited BH<sub>4</sub> deficiency. BH<sub>4</sub> supplementation has also drawn attention as a therapy for various NOS-related cardio-vascular diseases, but its use has met with limited success in decreasing BH<sub>2</sub>, the oxidized form of BH<sub>4</sub>. An increase in the BH<sub>2</sub>/BH<sub>4</sub> ratio leads to NOS dysfunction. Previous studies revealed that BH<sub>4</sub> supplementation caused a rapid urinary loss of BH<sub>4</sub> accompanied by an increase in the blood BH<sub>2</sub>/BH<sub>4</sub> ratio and an involvement of probenecid-sensitive but unknown transporters was strongly suggested in these processes. Here we show that OAT1 and OAT3 enabled cells to take up BP (BH<sub>4</sub> and/or BH<sub>2</sub>) in a probenecid-sensitive manner using rat kidney slices and transporter-expressing cell systems, LLC-PK1 cells and Xenopus oocytes. Both OAT1 and OAT3 preferred BH<sub>2</sub> and sepiapterin as their substrate roughly 5-to 10-fold more than BH<sub>4</sub>. Administration of probenecid acutely reduced the urinary exclusion of endogenous BP accompanied by a rise in blood BP in vivo. These results indicated that OAT1 and OAT3 played crucial roles: (1) in determining baseline levels of blood BP by excluding endogenous BP through the urine, (2) in the rapid distribution to organs of exogenous BH<sub>4</sub> and the exclusion to urine of a BH<sub>4</sub> excess, particularly when BH<sub>4</sub> was administered, and (3) in scavenging blood BH<sub>2</sub> by cellular uptake as the gateway to the salvage pathway of BH<sub>4</sub>, which reduces BH<sub>2</sub> back to BH<sub>4</sub>. << Less
Mol. Cell. Biochem. 435:97-108(2017) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.