Matches in SemOpenAlex for { <https://semopenalex.org/work/W2019954839> ?p ?o ?g. }
- W2019954839 endingPage "681" @default.
- W2019954839 startingPage "672" @default.
- W2019954839 abstract "Abstract Tyrosine hydroxylase (TH) is the rate‐limiting enzyme in the synthesis of catecholamine neurotransmitters. Primary inherited defects in TH have been associated with l ‐DOPA responsive and non‐responsive dystonia and infantile parkinsonism. In this study, we show that both the cofactor (6 R )‐ l ‐ erythro ‐5,6,7,8‐tetrahydrobiopterin (BH 4 ) and the feedback inhibitor and catecholamine product dopamine increase the kinetic stability of human TH isoform 1 in vitro . Activity measurements and synthesis of the enzyme by in vitro transcription–translation revealed a complex regulation by the cofactor including both enzyme inactivation and conformational stabilization. Oral BH 4 supplementation to mice increased TH activity and protein levels in brain extracts, while the Th ‐mRNA level was not affected. All together our results indicate that the molecular mechanisms for the stabilization are a primary folding‐aid effect of BH 4 and a secondary effect by increased synthesis and binding of catecholamine ligands. Our results also establish that orally administered BH 4 crosses the blood–brain barrier and therapeutic regimes based on BH 4 supplementation should thus consider the effect on TH. Furthermore, BH 4 supplementation arises as a putative therapeutic agent in the treatment of brain disorders associated with TH misfolding, such as for the human TH isoform 1 mutation L205P." @default.
- W2019954839 created "2016-06-24" @default.
- W2019954839 creator A5002837759 @default.
- W2019954839 creator A5027259737 @default.
- W2019954839 creator A5049867007 @default.
- W2019954839 creator A5055442295 @default.
- W2019954839 creator A5057736159 @default.
- W2019954839 creator A5061903765 @default.
- W2019954839 creator A5071057140 @default.
- W2019954839 date "2008-07-01" @default.
- W2019954839 modified "2023-10-12" @default.
- W2019954839 title "Tetrahydrobiopterin shows chaperone activity for tyrosine hydroxylase" @default.
- W2019954839 cites W1483218234 @default.
- W2019954839 cites W1514072575 @default.
- W2019954839 cites W1547084038 @default.
- W2019954839 cites W1550250656 @default.
- W2019954839 cites W1551789762 @default.
- W2019954839 cites W1851010840 @default.
- W2019954839 cites W1898832292 @default.
- W2019954839 cites W1900499785 @default.
- W2019954839 cites W1963798317 @default.
- W2019954839 cites W1963904928 @default.
- W2019954839 cites W1969720100 @default.
- W2019954839 cites W1971018350 @default.
- W2019954839 cites W1973413486 @default.
- W2019954839 cites W1979171380 @default.
- W2019954839 cites W1991103963 @default.
- W2019954839 cites W1994845503 @default.
- W2019954839 cites W1996409191 @default.
- W2019954839 cites W2002175191 @default.
- W2019954839 cites W2008716959 @default.
- W2019954839 cites W2011239911 @default.
- W2019954839 cites W2020929839 @default.
- W2019954839 cites W2023953960 @default.
- W2019954839 cites W2024522920 @default.
- W2019954839 cites W2024848503 @default.
- W2019954839 cites W2026064910 @default.
- W2019954839 cites W2026245843 @default.
- W2019954839 cites W2029666781 @default.
- W2019954839 cites W2031351234 @default.
- W2019954839 cites W2031875279 @default.
- W2019954839 cites W2046036275 @default.
- W2019954839 cites W2051616724 @default.
- W2019954839 cites W2052094887 @default.
- W2019954839 cites W2052306021 @default.
- W2019954839 cites W2061567693 @default.
- W2019954839 cites W2065461666 @default.
- W2019954839 cites W2067238110 @default.
- W2019954839 cites W2072754226 @default.
- W2019954839 cites W2073580602 @default.
- W2019954839 cites W2074975109 @default.
- W2019954839 cites W2080419647 @default.
- W2019954839 cites W2081011461 @default.
- W2019954839 cites W2086172007 @default.
- W2019954839 cites W2099857850 @default.
- W2019954839 cites W2104080537 @default.
- W2019954839 cites W2104387909 @default.
- W2019954839 cites W2106019968 @default.
- W2019954839 cites W2106453369 @default.
- W2019954839 cites W2107707818 @default.
- W2019954839 cites W2123725204 @default.
- W2019954839 cites W2124407773 @default.
- W2019954839 cites W2125013402 @default.
- W2019954839 cites W2126588700 @default.
- W2019954839 cites W2128399345 @default.
- W2019954839 cites W2133152748 @default.
- W2019954839 cites W2139139313 @default.
- W2019954839 cites W2142600698 @default.
- W2019954839 cites W2148460984 @default.
- W2019954839 cites W2152793449 @default.
- W2019954839 cites W2156248103 @default.
- W2019954839 cites W2157837974 @default.
- W2019954839 cites W2168138547 @default.
- W2019954839 cites W2168267395 @default.
- W2019954839 cites W31833952 @default.
- W2019954839 doi "https://doi.org/10.1111/j.1471-4159.2008.05423.x" @default.
- W2019954839 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18419768" @default.
- W2019954839 hasPublicationYear "2008" @default.
- W2019954839 type Work @default.
- W2019954839 sameAs 2019954839 @default.
- W2019954839 citedByCount "46" @default.
- W2019954839 countsByYear W20199548392013 @default.
- W2019954839 countsByYear W20199548392014 @default.
- W2019954839 countsByYear W20199548392015 @default.
- W2019954839 countsByYear W20199548392016 @default.
- W2019954839 countsByYear W20199548392017 @default.
- W2019954839 countsByYear W20199548392018 @default.
- W2019954839 countsByYear W20199548392019 @default.
- W2019954839 countsByYear W20199548392020 @default.
- W2019954839 countsByYear W20199548392021 @default.
- W2019954839 countsByYear W20199548392022 @default.
- W2019954839 countsByYear W20199548392023 @default.
- W2019954839 crossrefType "journal-article" @default.
- W2019954839 hasAuthorship W2019954839A5002837759 @default.
- W2019954839 hasAuthorship W2019954839A5027259737 @default.
- W2019954839 hasAuthorship W2019954839A5049867007 @default.
- W2019954839 hasAuthorship W2019954839A5055442295 @default.
- W2019954839 hasAuthorship W2019954839A5057736159 @default.