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Mechanism of inhibition of rat brain adenosine triphosphatase by mercuric chloride

Journal Article · · FASEB Journal (Federation of American Societies for Experimental Biology); (USA)
OSTI ID:6831869
Mercuric Chloride (Hg), a neurotoxic compound inhibited ATPase system of rat brain microsomes. Membrane bound enzymes, Na{sup +}-K{sup +} ATPase (IC{sub 50} = 2.35 {times} 10{sup {minus}7M}) and K-paranitrophenyl phosphatase (K-PNPPase) (IC{sub 50} = 2.7 {times} 10{sup {minus}7M}) and {sup 3}H-Ouabain binding (IC{sub 50} = 3.3 {times} 10{sup {minus}7M}) were inhibited by Hg at micromolar concentrations in a dose dependent manner. Hydrolysis of ATP was linear with time with or without Hg in the reaction mixtures. Altered pH or temperature versus enzyme activity showed higher inhibition by Hg at basic pH (8.0-9.0) and at lower temperatures (17-32{degree}C). Activation energy ({Delta}E) values were increased at 27-37{degree}C in the presence of Hg. Kinetic studies of cationic-substrate activation of Na{sup +}-K{sup +} ATPase and K-PNPPase in the presence of Hg showed significant changes in kinetic constant (K{sub m} and V{sub max}). Inhibition of Na{sup +}-K{sup +} ATPase was partially restored by repeated washings of microsomes. Preincubation with sulfhydryl agents protected Na{sup +}-K{sup +} ATPase from Hg inhibition. Cumulative inhibition studies with Hg and ouabain indicated possible interaction between the two inhibitors of Na{sup +}-K{sup +} ATPase by interacting at Na{sup +} and K{sup +} sites.
OSTI ID:
6831869
Journal Information:
FASEB Journal (Federation of American Societies for Experimental Biology); (USA), Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (USA) Vol. 3:3; ISSN FAJOE; ISSN 0892-6638
Country of Publication:
United States
Language:
English

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