 | Na,K-ATPase AND RELATED CATION PUMPS: Structure, Function, and Regulatory Mechanisms
Copyright © 2003 by the New York Academy of Sciences
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Annals of the New York Academy of Sciences 986:685-693 (2003)
© 2003 New York Academy of Sciences
11-Hydroxylation in the Biosynthesis of Endogenous Ouabain: Multiple Implications
JOHN M. HAMLYNa,
JAMES LAREDOa,
JUI R. SHAHa,
ZHUO REN LUa AND
BRUCE P. HAMILTONb,c
aDepartment of Physiology, bDepartment of Medicine, University of Maryland, Baltimore, Maryland 21201, USA
cVeterans Administration Medical Center, Baltimore, Maryland 21201, USA
Address for correspondence: John M. Hamlyn, Ph.D., FAHA, Department of Physiology, University of Maryland, 655 West Baltimore Street, Baltimore, MD 21201. Voice: 410-706-3479; fax: 410-706-8341.
jhamlyn{at}umaryland.edu
Ann. N.Y. Acad. Sci. 986: 685-693 (2003).
Accumulating evidence indicates that mammals use steroidal glycosides with "digitalis-like" activity. An endogenous ouabain (EO) has been described and is linked with long-term changes in sodium balance and cardiovascular structure and function. In the adrenal gland, the biosynthesis of EO and similar compounds appears to involve cholesterol side-chain cleavage with sequential metabolism of pregnenolone and progesterone. The more distal events in the biosynthesis have not been elucidated. Preliminary work using primary cell cultures from the bovine adrenal cortex suggests that the biosynthesis of EO is affected by inhibitors of 11ß-hydroxylase. Direct participation of 11-hydoxylase in EO synthesis would lead to an 11ß isomer of ouabain in mammals and, in vivo, an 11ß-oriented hydroxyl group would spontaneously form a mixture of two 11-19 hemiketal isomers. The latter isomers would likely be converted back to a single 11ß isomer of ouabain during isolation. The existence of an additional ring in the hemiketals, along with reduced flexion of the steroidal A, B, and C rings, raises the possibility that their in vivo physiological targets and actions differ from the isolated form of EO.
Key Words: metabolism • metyrapone • adrenal
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