On the Structure of Endogenous Ouabain

• Published in: Proceedings of the National Academy of Sciences - PNAS 1999-06, Vol.96 (12), p.6654-6659
• Main Authors: Kawamura, Akira, Guo, Jinsong, Itagaki, Yasuhiro, Bell, Charles, Wang, Yi, Haupert, Garner T., Magil, Sheila, Gallagher, Rex T., Berova, Nina, Nakanishi, Koji
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Biochemistry; Biological Sciences; Borates; Borosilicate glass; Brain Chemistry; Cattle; Chemical equilibrium; Chromatography, High Pressure Liquid; Enzymes; Hypothalamus - chemistry; Hypothalamus - metabolism; Isomers; Magnetic Resonance Spectroscopy; Molecules; Ouabain - chemistry; Ouabain - metabolism; Ouabain - pharmacology; Protein Conformation; Pumps; Sodium; Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors; Ungulates
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.12.6654

The ouabain-like sodium pump inhibitor in mammals (so-called "endogenous ouabain") has been considered a subtle structural isomer of ouabain. Its structural investigation, however, has long been hindered by the paucity of sample material. Our recent purification of endogenous ouabain (3 μ g) from bovine hypothalamus allowed the measurement of its 1H-NMR. The obtained spectrum as well as reexamination of past microscale structural studies on endogenous ouabain led us to identify the purified material as ouabain in an unusual manner. It turned out that the structural analysis had been complicated by a facile ouabain-borate complexation in borosilicate glassware. In retrospect, it is not surprising that the polyhydroxylated ouabain molecule serves as a polydentate ligand to inorganic species. In its physiological environment, ouabain may exist as some unknown complex. The chemical species giving rise to the reported biological activities of hypothalamic inhibitory factor preparations remain to be clarified.