Isoflurane’s Effect on Interfacial Dynamics in GAPDH Influences Methylglyoxal Reactivity
Document Type
Article
Publication Title
Archives of Biochemistry and Biophysics
Abstract
Diabetic surgical patients are at risk for peri- and post-operative complications, which can be prevented by maintaining tight glycemic control during anesthesia. Control of blood sugar would decrease unwanted chemical reactions, such as protein glycation, minimizing tissue dysfunction. Methylglyoxal (MG) is a major contributor to protein modification and tissue dysfunction seen in diabetic patients. We hypothesized that inhaled anesthetics may play a role in protein glycation and examined the effects of isoflurane on MG-induced modification of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Isoflurane promoted MG-induced modification of GAPDH as evidenced by an increase in fluorescent glycation products, a change in chromatographic elution patterns and a loss of enzyme activity. Isoflurane's effect may be mediated by altering interfacial events. Our working model involves the binding of isoflurane to GAPDH, increasing the susceptibility to MG-induced modification of residues involved in oligomerization. These findings suggest a molecular basis for maintaining glycemic control during anesthesia.
DOI
10.1016/j.abb.2010.04.001
Publication Date
6-1-2010
Keywords
Diabetes, Glycation, Glyceraldehyde-3-phosphate dehydrogenase, Isoflurane, Methylglyoxal
ISSN
1096-0384
Recommended Citation
Pattin AE, Ochs S, Theisen CS, Fibuch EE, Seidler NW. Isoflurane’s Effect on Interfacial Dynamics in GAPDH Influences Methylglyoxal Reactivity. Archives of Biochemistry and Biophysics. 2010; 498(1). doi: 10.1016/j.abb.2010.04.001.