Phenylketonuria
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop in Atlas of Inherited Metabolic Diseases, 2020
Phenylalanine hydroxylase, the defective enzyme in PKU, has a tetrahydrobiopterin cofactor that is required for the hydroxylation of phenylalanine. In the hydroxylase reaction, a quinonoid dihydrobiopterin is formed. The reduction of this compound to reform tetrahydrobiopterin is catalyzed by dihydropteridine reductase [33, 34]. The quinonoid oxidation product is unstable and, unless it is promptly reduced, it forms the 7, 8-dihydrobiopterin and is no longer a substrate for dihydropteridine reductase, but it can be reduced by dihydrofolate reductase in the presence of the reduced form of nicotinamide-adenosine dinucleotide phosphate (NADPH). The synthesis of biopterin begins with guanosine triphosphate and proceeds through reduced neopterin (α-D-erythro-7, 8-dihydroneopterin triphosphate) to a dihydro-precursor of tetrahydrobiopterin [35, 36].
Neurogenetics
John W. Scadding, Nicholas A. Losseff in Clinical Neurology, 2011
In patients with dystonia that is highly L-dopa responsive, a diagnosis of dopa-responsive dystonia (DRD/DYT5) should be considered. DRD is most commonly autosomal dominant with reduced penetrance, and caused by mutations in the gene for GTP-cycohydrolase 1, the enzyme required for tetrahydrobiopterin synthesis. This biopterin is in turn the cofactor for tyrosine hydroxylase, the enzyme required for dopamine synthesis. Mutations in the gene for tyrosine hydroxylase have also been identified that give rise to an autosomal recessive form of DRD.
Enzymes
Stephen W. Carmichael, Susan L. Stoddard in The Adrenal Medulla 1986 - 1988, 2017
Bigham, Smith, Reinhard et al. (1987) examined synthetic analogues of tetrahydrobiopterin that had cofactor activity for aromatic amino acid hydroxylases. They found that one of these compounds is an excellent cofactor for TH and other hydroxylases, does not destabilize the binding of substrate, and is recycled by dihydropteridine reductase. These compounds are being evaluated as cofactor replacements in biopterin-deficiency diseases.
Effects Of Endothelin-1 On Intracellular Tetrahydrobiopterin Levels In Vascular Tissue
Published in Scandinavian Cardiovascular Journal, 2018
Ruha Cerrato, Mark Crabtree, Charalambos Antoniades, Karolina Kublickiene, Ernesto L. Schiffrin, Keith M. Channon, Felix Böhm
We went on to investigate biopterin levels in ET-TG mice. The advantage of using ET-TG mice is that the long-term effects on biopterins of increased local endogenous ET-1 production in endothelial cells could be determined in aorta, lungs as well as plasma. However, even though there is 3-fold higher vascular tissue ET-1 mRNA content and 7-fold higher ET-1 plasma levels in this model [11], we could not see any effects on biopterins in these tissues. It may be due to that this phenotype is relatively healthy without overt atherosclerosis. In addition, oxidative stress and NADPH oxidase is increased in this model, which together with our findings collectively suggests that ET-1 affects NADPH oxidase rather than eNOS uncoupling in this model.
Urine as a biological modality for colorectal cancer detection
Published in Expert Review of Molecular Diagnostics, 2020
Subashini Chandrapalan, Ramesh P Arasaradnam
Neopterin is a metabolite of biopterin released from activated macrophages. Thus, it is a marker of cellular immunity. Weiss et al. [34] showed high Neopterin levels (above 220 μmol/mol of creatinine) were significantly (P = 0.0034) associated with poor prognosis in CRC in comparison to the group who had Neopterin levels below that level. Another retrospective study in a population with advanced or metastatic CRC showed that the survival of these patients was significantly longer when the urinary Neopterin concentrations were less than 214 μmol/mol creatinine [35]. A larger Hordaland health study [36] and a study by Aleksandrova and colleagues [37] also confirmed similar findings in plasma Neopterin levels.
Berberine suppresses the ectopic expression of miR-133a in endothelial cells to improve vascular dementia in diabetic rats
Published in Clinical and Experimental Hypertension, 2019
Sen Yin, Wenwu Bai, Peng Li, Xu Jian, Tichao Shan, Zhenyu Tang, Xuejiao Jing, Song Ping, Quanzhong Li, Zhang Miao, Shuangxi Wang, Wensheng Ou, Jianchun Fei, Tao Guo
The levels of BH4 were determined as previously described with some modification (21). Briefly, homogenates of tissues were suspended in distilled water containing 5 mM dithioerythrol, centrifuged at 12000 g at 4°C for 10 min, and then subjected to oxidation in acid or base. To 100 μl aliquot of supernatant, 20 μl of 0.5 M HCl and 0.05 M iodine were added for acidic oxidation, and 20 μl of 0.5 M NaOH plus 0.05 M iodine were added for basic oxidation. Biopterin concentrations were determined by HPLC with a PR-C18 column. Fluorescence was detected with an excitation at 350 nm and emission at 440 nm. BH4 concentrations were calculated as the difference in results from oxidation in acid and base.
Related Knowledge Centers
- Cofactor
- Nitric Oxide
- Norepinephrine
- Dopamine
- Neurotransmitter
- Serotonin
- Epinephrine
- Pterin
- Biopterin-Dependent Aromatic Amino Acid Hydroxylase
- Trace Amine