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Age-related effects in enzyme catalysis

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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.

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Abbreviations

CPL:

circular polarization of luminescence

DTNB:

5,5′-dithiobis (2-nitrobenzoic acid)

GPDH:

D-glyceraldehyde-3-phosphate dehydrogenase

εENAD+ :

nicotinamide 1,N6-ethenoadenine dinucleotide

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Author notes

  1. Art Gafni

    Present address: Molecular Biology Institute, University of California, 90024, Los Angeles, Los Angeles, CA, USA

  2. Noa Noy

    Present address: Veteran Administration Hospital, 4150 Clement Street, 94121, San Francisco, CA, USA

Authors and Affiliations

  1. Department of Chemical Physics, The Weizmann Institute of Science, 76100, Rehovot, Israel

    Art Gafni & Noa Noy

Authors
  1. Art Gafni
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Gafni, A., Noy, N. Age-related effects in enzyme catalysis. Mol Cell Biochem 59, 113–129 (1984). https://doi.org/10.1007/BF00231308

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