Mechanism of inhibition of purified leaping mullet (liza saliens) NADPH‐cytochrome P450 reductase by toxic metals: Aluminum and thallium

Abstract

Aluminum and thallium may reach life-threatening levels in aquatic systems in the near future because of their extensive use in various industrial fields. It is therefore important to study the mechanism of toxicity of aluminum and thallium on fish enzymes. To this aim, the effects of aluminum and thallium on the activity of purified leaping mullet (Liza saliens) cytochrome P450 reductase, an essential component of the important cytochrome P450 system, have been studied. Results indicated that both metal ions strongly inhibited the NADPH-cytochrome P450 reductase. The IC50 values of AlCl3 and TlCl3 were estimated to be 34 microM and 3 microM, respectively. The Lineweaver-Burk plot and Dixon plot revealed that both metal ions noncompetitively inhibited the purified mullet cytochrome P450 reductase. The K(i) values of Al3+ and Tl3+ were calculated from Dixon plots as 8.9 and 5.6 microM, respectively. The inhibitory effects of Al3+ and Tl3+ on purified cytochrome P450 reductase were partially recovered by 1 mM EDTA. Additionally, tin and magnesium were shown to have no apparent effect on purified mullet cytochrome P450 reductase.

The human xenobiotic‐metabolizing enzyme arylamine N‐acetyltransferase 1 (NAT1) is irreversibly inhibited by inorganic (Hg2+) and organic mercury (CH3Hg+): Mechanism and kinetics

“…It has been suggested that the inhibitory effects of mercuric compounds such as Hg 2+ and CH 3 Hg + on certain XME (such as UDP‐glucuronyltransferases) is of importance, as the alteration of their activity may lead to generation and/or accumulation of hazardous xenobiotics [16,18]. Our data adds to this and suggest that in addition to UDP‐glucuronyltransferases and glutathione S ‐transferases, NAT1 is a phase II‐XME sensitive to low levels of mercuric pollutants.…”

“…These chemicals can alter protein functions by interaction with important sulfhydryl groups [14,15]. Hg 2+ can inhibit enzymes containing reactive thiols groups in or near their active site [14,16]. Certain studies suggest that inhibition of xenobiotic‐metabolizing enzymes (XMEs) by mercury may represent an important mechanism in mercury toxicity [16–18].…”

“…Hg 2+ can inhibit enzymes containing reactive thiols groups in or near their active site [14,16]. Certain studies suggest that inhibition of xenobiotic‐metabolizing enzymes (XMEs) by mercury may represent an important mechanism in mercury toxicity [16–18]. In addition, rabbit liver NAT have been shown to be inhibited by 4‐chloromercurybenzoic [19].…”

Purification and characterization of NADPH-cytochrome P450 reductase from Lake Van fish liver microsomes and investigation of some chemical and metals' effects on the enzyme activity

“…In other conducted studies, it was determined that Tl 3+ inhibited leaping mullet liver CPR enzyme in vitro, 29 whereas Pb 2+ , Cd 2+ , and Ni 2+ inhibited bovine liver CPR enzyme 48 in vitro. In the conducted studies, it was reported that Al 3+ and Hg 2+ noncompetitively inhibited leaping mullet liver CPR enzyme, 29,31 Cu 2+ ion competitively inhibited leaping mullet liver CPR enzyme, and Cu 2+ inhibited and affected liver P450 monooxygenase enzyme system, P450s, and CPR enzyme. 47 Levesque et al reported that constant exposure to heavy metal ions below the lethal level caused growth disorders and change in the lipid metabolism in fish.…”

“…In recent years, the aquatic system has been exposed to metal pollution as a result of the rapid development in industry. 29 Metals can be hazardous for living organisms at a lethal level since they have the property of spreading in nature and penetrating into living organisms. For instance, metals have the tendency to accumulate in some tissues of the human body, and they have a potential toxic effect, even in low amounts of exposure.…”