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PMID: 10657232 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review

Thioredoxin reductase.

The Biochemical journal ·Vol. 346 Pt 1 ·2000-02-15 ·Pages 1-8

Mustacich D, Powis G

Abstract

The mammalian thioredoxin reductases (TrxRs) are a family of selenium-containing pyridine nucleotide-disulphide oxidoreductases with mechanistic and sequence identity, including a conserved -Cys-Val-Asn-Val-Gly-Cys- redox catalytic site, to glutathione reductases. TrxRs catalyse the NADPH-dependent reduction of the redox protein thioredoxin (Trx), as well as of other endogenous and exogenous compounds. The broad substrate specificity of mammalian TrxRs is due to a second redox-active site, a C-terminal -Cys-SeCys- (where SeCys is selenocysteine), that is not found in glutathione reductase or Escherichia coli TrxR. There are currently two confirmed forms of mammalian TrxRs, TrxR1 and TrxR2, and it is possible that other forms will be identified. The availability of Se is a key factor determining TrxR activity both in cell culture and in vivo, and the mechanism(s) for the incorporation of Se into TrxRs, as well as the regulation of TrxR activity, have only recently begun to be investigated. The importance of Trx to many aspects of cell function make it likely that TrxRs also play a role in protection against oxidant injury, cell growth and transformation, and the recycling of ascorbate from its oxidized form. Since TrxRs are able to reduce a number of substrates other than Trx, it is likely that additional biological effects will be discovered for TrxR. Furthermore, inhibiting TrxR with drugs may lead to new treatments for human diseases such as cancer, AIDS and autoimmune diseases.

MeSH Terms
Animals Ascorbic Acid/metabolism Cell Division Disease Gene Expression Regulation, Enzymologic Humans Oxidative Stress Selenium/metabolism Selenocysteine/metabolism Thioredoxin-Disulfide Reductase/chemistry,genetics,metabolism Tumor Suppressor Protein p53/metabolism
Chemicals
Tumor Suppressor Protein p53 Selenocysteine Thioredoxin-Disulfide Reductase Selenium Ascorbic Acid
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Mustacich D
Arizona Cancer Center, University of Arizona, 1515 N. Campbell Avenue, Tucson, AZ 85724-5024, USA.
Powis G
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
Published
2000-02-15
Pages
1-8
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1220815
Subset
IM
Grants
NCI NIH HHS · CA77204 · United States
NCI NIH HHS · CA78277 · United States
NCI NIH HHS · F32CA79106 · United States
External Links
PubMed source PMC Full Text View journal details
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