Age-related effects in enzyme catalysis.
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.
D000227:Adenine Nucleotides / Q000378:metabolism; D000375:Aging; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002384:Catalysis; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000032:analysis / Q000302:isolation & purification / Q000378:metabolism*; D009132:Muscles / Q000201:enzymology; D009243:NAD / Q000378:metabolism; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D013057:Spectrum Analysis
D000227:Adenine Nucleotides; D000596:Amino Acids; D009243:NAD; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases