The University of Dublin | Trinity College -- Ollscoil Átha Cliath | Coláiste na Tríonóide
Trinity's Access to Research Archive
Home :: Log In :: Submit :: Alerts ::

TARA >
School of Biochemistry & Immunology >
Biochemistry >
Biochemistry (Scholarly Publications) >

Please use this identifier to cite or link to this item: http://hdl.handle.net/2262/64120

Title: Queuosine deficiency in eukaryotes compromises tyrosine production through increased tetrahydrobiopterin oxidation.
Author: RAKOVICH, TATSIANA
KELLY, VINCENT PATRICK
BERNSTEIN, IIANA
Boland, Colin
Author's Homepage: http://people.tcd.ie/kellyvp
http://people.tcd.ie/ibernste
Keywords: Biochemistry
Queuosine
pyrrolopyrimidine nucleoside
RNA
HepG2 cells
Issue Date: 2011
Publisher: American Society for Biochemistry and Molecular Biology
Citation: Rakovich T, Boland C, Bernstein I, Chikwana VM, Iwata-Reuyl D, Kelly VP, Queuosine deficiency in eukaryotes compromises tyrosine production through increased tetrahydrobiopterin oxidation., The Journal of Biological Chemistry, 2011
Series/Report no.: The Journal of Biological Chemistry;
Abstract: Queuosine is a modified pyrrolopyrimidine nucleoside found in the anticodon loop of transfer RNA acceptors for the amino acids tyrosine, asparagine, aspartic acid, and histidine. Since it is exclusively synthesised by bacteria, higher eukaryotes must salvage queuosine or its nucleobase queuine from food and the gut microflora. Previously, animals made deficient in queuine died within 18 days of withdrawing tyrosine-a non-essential amino acid-from the diet [Marks T, Farkas WR (1997) Biochem Biophys Res Commun 230:233-7]. Here we show that human HepG2 cells deficient in queuine and mice made deficient in queuosine modified transfer RNA, by disruption of the tRNA guanine transglycosylae (TGT) enzyme, are compromised in their ability to produce tyrosine from phenylalanine. This has similarities to the disease phenylketonuria, which arises from mutation in the enzyme phenylalanine hydroxylase or from a decrease in the supply of its cofactor tetrahydrobiopterin (BH4). Immunoblot and kinetic analysis of liver from TGT deficient animals indicate normal expression and activity of phenylalanine hydroxylase. By contrast, BH4 levels are significantly decreased in the plasma and both plasma and urine show a clear elevation in dihydrobiopterin, an oxidation product of BH4, despite normal activity of the salvage enzyme dihydrofolate reductase. Our data suggest that queuosine modification limits BH4 oxidation in vivo and thereby potentially impacts on numerous physiological processes in eukaryotes.
Description: IN_PRESS
URI: http://hdl.handle.net/2262/64120
Related links: http://www.jbc.org/content/early/2011/04/12/jbc.M111.219576
Appears in Collections:Biochemistry (Scholarly Publications)

Files in This Item:

File Description SizeFormat
Queuosine deficiency in eukaryotes compromises tyrosine production through increased tetrahydrobiopterin oxidation.pdfAccepted for publication (author's copy) - Peer Reviewed930.88 kBAdobe PDFView/Open


This item is protected by original copyright


Please note: There is a known bug in some browsers that causes an error when a user tries to view large pdf file within the browser window. If you receive the message "The file is damaged and could not be repaired", please try one of the solutions linked below based on the browser you are using.

Items in TARA are protected by copyright, with all rights reserved, unless otherwise indicated.

 

Valid XHTML 1.0! DSpace Software Copyright © 2002-2010  Duraspace - Feedback