Inhibition of camel lens ζ-crystallin by aspirin and aspirin-like analgesics

Camel lens ζ-crystallin was reversibly inhibited to various degrees by aspirin (acetyl salicylic acid) and the aspirin-like analgesics: paracetamol (acetaminophen) and ibuprofen (2-(4-isobutyl phenyl)-propionic acid). Among these, aspirin was the most potent inhibitor, causing nearly complete inhibi...

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Bibliographic Details
Published in:The international journal of biochemistry & cell biology 2002, Vol.34 (1), p.70-77
Main Authors: Bazzi, Mohammad D, Rabbani, Nayyar, Duhaiman, Ali S
Format: Article
Language:English
Subjects:
Acetaminophen - pharmacology
Analgesics - pharmacology
Animals
Aspirin
Aspirin - pharmacology
Binding Sites
Binding, Competitive
Camel lens
Camelus
Crystallins - antagonists & inhibitors
Crystallins - chemistry
Crystallins - metabolism
Ibuprofen - pharmacology
In Vitro Techniques
Inhibition
Kinetics
Lysine - chemistry
NADP - metabolism
Phenanthrenes - pharmacology
Pyridoxal Phosphate - pharmacology
ζ-Crystallin
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Summary:Camel lens ζ-crystallin was reversibly inhibited to various degrees by aspirin (acetyl salicylic acid) and the aspirin-like analgesics: paracetamol (acetaminophen) and ibuprofen (2-(4-isobutyl phenyl)-propionic acid). Among these, aspirin was the most potent inhibitor, causing nearly complete inhibition in a dose-dependent, but time-independent manner. Analysis of inhibition kinetics revealed that aspirin was uncompetitive inhibitor ( K i 0.64 mM) with respect to NADPH and non-competitive inhibitor ( K i 1.6 mM) with respect to the substrate, 9,10-phenanthrenequinone (PQ). Multiple-inhibition analysis showed that aspirin and pyridoxal 5′ phosphate (PAL-P), a lysine specific reagent, simultaneously bound to a critical lysine residue located towards the NADPH binding region. Consistent with this, NADPH was able to substantially protect ζ-crystallin against aspirin, whereas PQ did not provide any protection. The results suggested that an essential lysine residue was the locus of aspirin binding. The inhibition of ζ-crystallin by aspirin and aspirin-like analgesics was reversible thus eliminating acetylation as a mechanism for inhibition. Reversible binding of aspirin to this lysine may cause steric hindrance resulting in uncompetitive inhibition with respect to NADPH.
ISSN:1357-2725
1878-5875
DOI:10.1016/S1357-2725(01)00099-1