Studies on superoxide dismutase inhibition and application of methods to study metal ion participation in complication of diabetes
- WCU Author/Contributor (non-WCU co-authors, if there are any, appear on document)
- Benjamin Hickman (Creator)
- Institution
- Western Carolina University (WCU )
- Web Site: http://library.wcu.edu/
- Advisor
- Jack Summers
Abstract: Studies on Superoxide Dismutase Inhibition
We used NMR relaxation rates to study reactions of the enzyme superoxide dismutase
(SOD) with low molecular weight polyphenolic compounds. While the compounds appeared to
inhibit SOD, we discovered evidence that the reaction proceeds with electron transfer from the
polyphenols to the enzyme, giving a form of the SOD that was inactive in the assay but retained
enzymatic activity. The reaction was highly dependent on the aggregation and protonation states
of the compounds.
Application of Methods to Study Metal Ion Participation in Complication of Diabetes
Diabetics display increases in chemical modification of proteins and also increased levels
of oxidative stress. Alderson et al. reports one of these modifications involves reaction of the sulfhydryl group of cysteine residues with the Krebs Cycle intermediate fumarate. It has been
proposed that the product, S-(2-Succinyl)cysteine (2SC), can bind metals, and may catalyze
reactions such as the Haber-Weiss cycle. It is possible that 2SC will catalyze the
disproportionation of superoxide. To study the possible link between 2SC and oxidative stress we
synthesized two model compounds and studied their reactions. One of these is S-(2-succinyl)-Nacetlycysteine
(2SAC). We have shown the 2SAC will bind copper with a stability constant of
log(K)= 3.59 ± 0.05. Also we have shown that the compound 2SAC-Cu will catalyze the Haber-
Weiss reaction but not the disproportination of superoxide. Furthermore, since glutathione
concentrations in vivo can reach up to 10 mM it seems likely that reduced glutathione will react
with fumerate to give S-(2-succinyl)-glutathione (2SGT). To study its possible role in vivo, we
synthesized 2SGT. For the 2SGT compound, the binding constant of Cu-2SGT was determined to
be log(K)=10.9 ± 0.2. Likewise, we have found that 2SGT binds to copper in such a way as to
prevent catalysis of further reactions. Our attempts to study the iron complexes for these
compounds have been unsuccessful due to their low solubility.
Studies on superoxide dismutase inhibition and application of methods to study metal ion participation in complication of diabetes
PDF (Portable Document Format)
23278 KB
Created on 5/30/2012
Views: 2804
Additional Information
- Publication
- Thesis
- Language: English
- Date: 2012
- Keywords
- diabetes, flavonols, oxidative stress, superoxide dismutase
- Subjects
- Superoxide dismutase -- Inhibitors
- Diabetes