The oxygen carrying function of our blood depends on the structure of hemoglobin packed in red blood cells. Changes in the structure of hemoglobin often result in aberrations of the functional behavior and pathological conditions such as sickle cell anemia, hemolysis and cyanosis among others. This proposal is directed towards the key area of understanding the functional behavior or hemoglobin on a molecular basis. An attempt is being made to study the mechanism of cooperativity in the ligation reaction of isomers of the partially liganded species: Hb4L, Hb4L2, and Hb4L3. The geminate reaction of ligands with various hemoglobins will be studied to examine the effect of tertiary and quaternary structural changes on the geminate reaction and to relate it to the overall ligand reactivity. These studies will be made on M-hemoglobins, Hb Zurich, carp hemoglobin, opossum hemoglobin, human Hb A, and myglobins of elephant and aplysia. These hemoglobins have been selected for the study because they involve substitution at important positions in the heme pocket or they can switched to the two quaternary structures of hemoglobin simply by changing the pH of solution and/or adding inositolhexaphosphate. In addition to this, studies will also be made on some ferro and ferric model compounds using nitric oxide as the ligand. The techniques to be used, among others, are double mixing rapid kinetics and micro-second and nano-second flash-photolysis kinetics. The human hemoglobins chosen above are all of clinical interest.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL031159-10
Application #
3342179
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1976-09-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
10
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093