Hypoxia inhibits l-arginine synthesis from l-citrulline in porcine
pulmonary artery endothelial cells.
Su, Yunchao, and Edward R. Block.
Medical Research Service of the Veterans Affairs Medical Center and
the Department of Medicine, University of Florida College of
Medicine, Gainesville, FL 32608-1197 U.S.A.
APStracts 2:0122L, 1995.
Both non-arginine-depleted and arginine-depleted pulmonary artery
endothelial cells (PAEC) actively convert citrulline into arginine.
Exposure to hypoxia for 4-24 h inhibited arginine synthesis from
citrulline in intact cells and in cell homogenates. The conversion of
L-citrulline to L-argininosuccinate by argininosuccinate synthetase
(AS) was inhibited by exposure to hypoxia for 4, 12, or 24 h. The
conversion of argininosuccinate to arginine by argininosuccinate
lyase was inhibited by exposure to hypoxia for 24 h but not for 4-12
h. The decrease of L-arginine biosynthesis during hypoxia coincided
with the increase of intracellular glutamine content and was
abrogated by preventing an increase in intracellular glutamine. In
addition, AS activity was inversely related to glutamine content in
the medium. These results indicate that hypoxia inhibited the L
-arginine biosynthetic pathway via decreased activity of AS. The
latter is related to increased glutamine content. Hypoxic inhibition
of arginine synthesis from citrulline did not result in a decrease of
arginine content, suggesting that PAEC are able to maintain
intracellular arginine for up to 24 h despite reduction in the L
-arginine biosynthetic pathway.
Received 9 February 1995; accepted in final form 8 June 1995.
APS Manuscript Number L49-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.