In certain senile cataracts, lens opacification is accompanied by abnormal lenticular Na+ and/or K+ concentrations. These abnormal monovalent cation concentrations may or may not result from malfunction of the plasma membrane bound Na,K-ATPase. The Na,K-ATPase has many essential amino acid side chains whose modifications could lead to malfunction while the enzymatic function of Na,K-ATPase, the hydrolysis of near-saturating levels of ATP, would remain unchanged. It has already been demonstrated that H2O2 modification of Na,K-ATPase in the organ cultured bovine lens essentially inhibits K+ transport while leaving the hydrolysis of near saturating levels of ATP essentially normal. However, oxidation of Na,K-ATPase is not the only route by which pump function can be altered. The enzyme is known to have certain amino functional groups (Bohr groups) whose titration in the physiological range control the conformational state of the enzyme. The transport of Na+ and K+ is linked intimately to the interconversion of the enzyme between its two conformational states. Therefore, modification of these Bohr groups might be expected to significantly alter the transport function of Na,K-ATPase. Since the pH range in which the Bohr groups of Na,K-ATPase titrate is similar to the NH2 terminal groups of the Alpha and Beta chains of hemoglobin, in vivo post-translational glycosylation, carbamylation or alkylation might occur in disease states such as uncontrolled diabetes, uremia or drug therapy. To this end, the in vitro reaction of the Bohr amines of Na,K-ATPase with glucose, cyanate and selected alkylating agents followed by characterization of enzymatic function should yield valuable information regarding the possible in vivo modification of the enzyme with similar agents.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY005918-01
Application #
3261614
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1985-07-10
Project End
1986-06-30
Budget Start
1985-07-10
Budget End
1986-06-30
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027