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Interaction of α-diketones with arginine residues leads to Proteasomal dysfunction
Key Event Relationship Overview
AOPs Referencing Relationship
Life Stage Applicability
Key Event Relationship Description
α-diketones are able to react with proteins, predominantly by covalent binding with arginine residues. This interaction with proteins can affect their structure and compromise their function. Arginine-rich proteins or enzymes with arginine residues at active sites are likely the critical molecular targets.
Evidence Collection Strategy
Evidence Supporting this KER
The toxic effects of the electrophilic α-diketones are likely associated with their direct covalent interactions with cellular nucleophiles. In this way, α-diketones react with proteins, displaying a great affinity for arginine residues. Since arginine residues are often located at the active sites of enzymes the interaction with α-diketones can cause loss of enzyme activity. Also the interaction with other proteins can result in altered structure and function.
Uncertainties and Inconsistencies
The target proteins are likely arginine-rich proteins or enzymes containing arginine residues at their active sites. However, at present it is unclear which proteins are the critical targets for the observed toxicity after the inhalation of α-diketones.
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
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