Characterization of zeta-crystallin inhibition by juglone.
Guinea pig lens zeta-crystallin showed hyperbolic saturation curves with 9,10-phenanthrenequinone (PAQ). 5-hydroxy-1,4-naphthoquinone (juglone) and NADPH. Whereas camel lens zeta-crystallin showed hyperbolic saturation curves only with PAQ and NADPH, but slightly segmoidal with juglone. For both enzymes PAQ was the preferred substrate. The catalytic center activity (Kcat) values indicated that camel zeta-crystallin catalyzed the reduction of PAQ more efficiently than the guinea pig lens zeta-crystallin, although the Km values of the two enzymes for this quinone were very similar. The guinea pig lens zeta-crystallin catalyzed the reduction of Juglone far more efficiently than that of the camel lens zeta-crystallin. Juglone did not serve as an efficient substrate for both zeta-crystallins compared to PAQ and appeared to act as a potent competitive inhibitor, with Kl values of 75 nM and 20 microM for guinea pig lens zeta-crystallin and camel lens zeta-crystallin, respectively. Thus, the camel lens zeta-crystallin was less active toward juglone as a substrate as well as less sensitive to its inhibitory action, when compared with guinea pig lens zeta-crystallin. The inhibition mechanism of guinea pig and camel lens zeta-crystallin by juglone is discussed.
Duhaiman
A S
AS
Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
D000818:Animals; D002162:Camelus; D003459:Crystallins / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D007700:Kinetics; D009249:NADP / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D010616:Phenanthrenes / Q000378:metabolism; D011808:Quinone Reductases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D003459:Crystallins; D004791:Enzyme Inhibitors; D009285:Naphthoquinones; D010616:Phenanthrenes; C005399:9,10-phenanthrenequinone; D009249:NADP; D011808:Quinone Reductases; C005134:juglone