Carbonyl-Induced Enzyme Inhibition: Mechanisms and New Perspectives
Document Type
Article
Publication Title
Current Enzyme Inhibition
Abstract
While agents that cause carbonyl-induced modification include sugars, lipids and industrial and pyrogenic compounds, much of the existing literature describes the process of glycation. Protein glycation is recognized as a major post-translational modification that attends the pathogenesis of diverse diseases. Glycation arises from the reactivity of common carbohydrates, their metabolic intermediates and their oxidized byproducts. The hyperglycemia associated with diabetes and the life-long exposure to pro-glycating agents bring about an environment that favors the modification of diverse proteins resulting in macro- and microangiopathy and the neuropathy of misfolding disorders such as Alzheimers disease. Numerous structural and catalytic proteins have been shown to be targets of glycation. The literature documents the potent inhibitory effects of glycation with very insightful suggestions on mechanisms of action. The current review describes the way carbonyl-containing (and particularly glycating) agents react with protein residues elucidating mechanisms that include two broad categories: direct reaction (1) with active site residues and (2) with residues distinct from the active site. The consequence of active site modification involves obvious steric and chemical changes that are likely to be prohibitive. The modification of residues distinct from the active site suggests inhibitory mechanisms more subtle and complex. The current review presents new perspectives in this emerging field that has implications beyond enzyme inhibition, such as the cellular impact of protein insolubility and aggregation.
DOI
10.2174/1573408052952720
Publication Date
2005
Keywords
glycation, advanced glycation endproducts, enzyme inhibition, post-translational modification, active site
ISSN
1875-6662
Recommended Citation
Seidler NW. Carbonyl-Induced Enzyme Inhibition: Mechanisms and New Perspectives. Current Enzyme Inhibition. 2005; 1(1). doi: 10.2174/1573408052952720.
