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Plasma fatty acid levels may regulate the Zn(2+)-dependent activities of histidine-rich glycoprotein.
MedLine Citation:
PMID:  19679159     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
Histidine-rich glycoprotein (HRG) is a plasma adaptor protein involved in the formation of protein complexes that regulate a number of biological processes in the blood, most notably coagulation and the immune system. Elevated levels of HRG are clinically linked to thrombotic disorders such as blood vessel occlusion. A large body of evidence suggests that Zn(2+) ions stimulate HRG-complex formation; however, under normal conditions the vast majority of Zn(2+) in the blood is bound to human serum albumin (HSA). We have previously demonstrated that high levels of fatty acid act as an allosteric switch which disrupts the major Zn(2+)-binding site on HSA. Transient or sustained elevation of plasma fatty acid levels may therefore increase the proportion of plasma Zn(2+) associated with HRG. We speculate that this mechanism may potentiate an increased risk of thrombosis in individuals with elevated fatty acid levels such as those associated with cancer, obesity and diabetes.
Authors:
Alan J Stewart; Claudia A Blindauer; Peter J Sadler
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-08-11
Journal Detail:
Title:  Biochimie     Volume:  91     ISSN:  1638-6183     ISO Abbreviation:  Biochimie     Publication Date:    2009 Nov-Dec
Date Detail:
Created Date:  2009-11-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1264604     Medline TA:  Biochimie     Country:  France    
Other Details:
Languages:  eng     Pagination:  1518-22     Citation Subset:  IM    
Affiliation:
Bute Medical School, University of St. Andrews, Bute Building, St. Andrews, Fife KY16 9TS, UK. ajs21@st-andrews.ac.uk
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