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J. Biol. Chem., Vol. 276, Issue 47, 43740-43747, November 23, 2001
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From the Department of Biochemistry, Memorial University of
Newfoundland, St. John's, Newfoundland A1B 3X9, Canada
An elevated plasma level of homocysteine is a
risk factor for the development of cardiovascular disease. The purpose
of this study was to investigate the effect of glucagon on homocysteine metabolism in the rat. Male Sprague-Dawley rats were treated with 4 mg/kg/day (3 injections per day) glucagon for 2 days while control rats
received vehicle injections. Glucagon treatment resulted in a 30%
decrease in total plasma homocysteine and increased hepatic activities
of glycine N-methyltransferase, cystathionine
Hyperglucagonemia in Rats Results in Decreased Plasma
Homocysteine and Increased Flux through the Transsulfuration Pathway in
Liver*
§,
-synthase, and cystathionine 
-lyase. Enzyme activities of the remethylation pathway were unaffected. The 90% elevation in activity of
cystathionine -synthase was accompanied by a 2-fold increase in its
mRNA level. Hepatocytes prepared from glucagon-injected rats
exported less homocysteine, when incubated with methionine, than did
hepatocytes of saline-treated rats. Flux through cystathionine
-synthase was increased 5-fold in hepatocytes isolated from
glucagon-treated rats as determined by production of
14CO2 and
-[1-14C]ketobutyrate from
L-[1-14C]methionine. Methionine transport was
elevated 2-fold in hepatocytes isolated from glucagon-treated rats
resulting in increased hepatic methionine levels. Hepatic
concentrations of S-adenosylmethionine and
S-adenosylhomocysteine, allosteric activators of
cystathionine -synthase, were also increased following glucagon
treatment. These results indicate that glucagon can regulate plasma
homocysteine through its effects on the hepatic transsulfuration pathway.
*
This work was supported in part by a grant from the Canadian
Diabetes Association.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of a Canada Institute of Health Research Doctoral Fellowship.
¶
Received a K. M. Hunter/Canadian Institutes for Health
Research Doctoral Fellowship.
To whom correspondence should be addressed. Tel.:
709-737-8540; Fax: 709-737-2422; E-mail: jbrosnan@mun.ca.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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