Lipid peroxidation products, such as 4-hydroxy-2-nonenal and malondialdehyde, have previously been shown to cause structural changes to proteins including introduction of carbonyl groups into amino acid side chains. The level of carbonyl groups has proven to be a valuable measure of oxidative protein damage associated with aging, oxidative stress, and a number of diseases. Metal-catalyzed oxidation of glutamine synthetase and bovine serum albumin and the effect of polyunsaturated fatty acids are under investigation. For both proteins, higher levels of carbonyl derivatives are formed by ascorbate and iron when linolenic acid is added to the incubation mixture. Formation of carbonyl groups in bovine serum albumin in the presence of linolenic acid was simultaneous with loss of histidine and lysine residues and fragmentation. Future studies will focus on the molecular mechanism of protein oxidation in the presence of lipids.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Intramural Research (Z01)
Project #
1Z01HL000318-01
Application #
6162658
Study Section
Special Emphasis Panel (LB)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Refsgaard, H H; Tsai, L; Stadtman, E R (2000) Modifications of proteins by polyunsaturated fatty acid peroxidation products. Proc Natl Acad Sci U S A 97:611-6