Muscle as the Primary Site of Urea Cycle Enzyme Activity in an Alkaline Lake-adapted Tilapia, Oreochromis alcalicus grahami

doi:10.1074/jbc.274.42.29858

Muscle as the Primary Site of Urea Cycle Enzyme Activity in an Alkaline Lake-adapted Tilapia, *Oreochromis alcalicus grahami**

From the ^‡Department of Biochemistry and Molecular Biology, University of Minnesota-Duluth, Duluth, Minnesota 55812, the ^§Rosenstiel School of Marine and Atmospheric Science, University of Miami, Miami, Florida 33149-1098, the ^¶Department of Biology, McMaster University, Hamilton, Ontario L8S4K1, Canada, and the ^‖Department of Zoology and Physiology, University of Wyoming, Laramie, Wyoming 82071

Abstract

The tilapia fish Oreochromis alcalicus grahami from Kenya has adapted to living in waters at pH 10.5 by excreting the end product of nitrogen metabolism as urea rather than as ammonia directly across the gills as occurs in most fish. The level of activity in liver of the first enzyme in the urea cycle pathway, carbamoyl-phosphate synthetase III (CPSase III), is too low to account for the observed high rates of urea excretion. We report here the surprising finding that CPSase III and all other urea cycle enzyme activities are present in muscle of this species at levels more than sufficient to account for the rate of urea excretion; in addition, the basic kinetic properties of the CPSase III appear to be different from those of other known type III CPSases. The sequence of the CPSase III cDNA is reported as well as the finding that glutamine synthetase activity is present in liver but not in muscle. This unusual form of adaptation may have occurred because of the apparent impossibility of packaging the needed amount of urea cycle enzymes in liver.

Footnotes

↵* This work was supported by National Science Foundation Grants IBN-9727741 (to P. M. A.) and IBN-9507239 (to P. J. W.) and by grants from the National Sciences and Engineering Research Council of Canada (to C. M. W.) and the University of Wyoming and the Fulbright Foundation (to H. J. B.).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.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank™/EMBL Data Bank with accession number(s) .
↵** To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology, School of Medicine, University of Minnesota-Duluth, Duluth, MN 55812. Tel.: 218-726-7921; Fax: 218-726-8014; E-mail: panderso@d.umn.edu.
↵2 P. J. Walsh, unpublished data.
Abbreviations:

CPSase

carbamoyl-phosphate synthetase

GSase

glutamine synthetase

AGA

N-acetyl-l-glutamate

PAGE

polyacrylamide gel electrophoresis
- Received May 3, 1999.
- Revision received August 5, 1999.
The American Society for Biochemistry and Molecular Biology, Inc.