Age-related effects in enzyme catalysis |
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Authors: | Art Gafni Noa Noy |
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Institution: | (1) Department of Chemical Physics, The Weizmann Institute of Science, 76100 Rehovot, Israel;(2) Present address: Molecular Biology Institute, University of California, 90024 Los Angeles, Los Angeles, CA, USA;(3) Present address: Veteran Administration Hospital, 4150 Clement Street, 94121 San Francisco, CA, USA |
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Abstract: | Summary Rat muscle glyceraldehyde-3-phosphate dehydrogenase is one of several enzymes which have been found to undergo age-related modifications. While the amount of this enzyme in muscle tissue does not change with age, both its specific activity and affinity towards its co-enzyme are significantly reduced in the old tissue.Age-related structural changes were found to exist in the nicotinamide binding site of the enzyme and the reactions leading to the activity loss in old glyceraldehyde-3-phosphate dehydrogenase were shown to involve a reversible modification of the essential cysteine-149 residue at the active site of the enzyme. The aging effects were simulated by a controlled oxidation of cys-149 in samples of young glyceraldehyde-3-phosphate dehydrogenase and subsequent reduction of this residue by 2-mercaptoethanol. The enzyme modified in this way closely resembles native old glyceraldehyde-3-phosphate dehydrogenase, indicating that the structural modifications in the latter enzyme are indeed introduced by a post-translational process. The mechanism for aging of glyceraldehyde-3-phosphate dehydrogenase which is proposed, based on these observations, thus assumes an oxidation of cys-149 as its first step followed by irreversible conformational changes in the enzyme molecule. The aging of glyceraldehyde-3-phosphate dehydrogenase may thus be triggered by the reduced ability of old muscle tissue to protect its constituents against oxidation.Abbreviations CPL
circular polarization of luminescence
- DTNB
5,5-dithiobis (2-nitrobenzoic acid)
- GPDH
D-glyceraldehyde-3-phosphate dehydrogenase
- ENAD+
nicotinamide 1,N6-ethenoadenine dinucleotide |
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