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Title: Liver Zn-thionein (ZnMT) regulates the interaction of Zn and Pb with delta-aminolevulinic acid dehydratase (ALAD)

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6365985

ZnMT has been postulated to function in essential metal homeostasis and metal detoxication. This study was undertaken to evaluate the potential of liver ZnMT to mediate the interaction of Zn and Pb with the Zn metalloenzyme, ALAD. Pretreatment of rats with Zn activated liver ALAD and attenuated the inhibition of ALAD by Pb in vitro and in vivo. Liver cytosol from Zn-pretreated rats injected with /sup 203/Pb was fractionated via gel filtration and anion-exchange chromatography and disclosed that both Zn and /sup 203/Pb co-eluted in the MT fractions. Both purified ZnMT-I and ZnMT-II bound /sup 203/Pb in vitro as shown by gel filtration chromatography. Addition of purified liver ZnMT to purified bovine liver ALAD reaction mixtures increased enzyme activity by 2-fold and prevented inhibition of ALAD by Pb. Addition of apothionein alone decreased the activity of Zn-activated ALAD and also attenuated Pb inhibition of the enzyme. Gel filtration studies of incubates containing /sup 65/ZnMT demonstrated that Zn was transferred from MT to ALAD. Fractionation of incubates containing /sup 203/Pb demonstrated that ZnMT sequestered Pb away from ALAD. These data suggest that MT may function to regulate the activity of some Zn-metalloenzymes, such as ALAD, by controlling Zn availability and that it may also alter the interaction of Pb with ALAD by decreasing the cytosolic pool of free Pb.

Research Organization:
NIEHS, Research Triangle Park, NC
OSTI ID:
6365985
Report Number(s):
CONF-870644-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 46:6; Conference: 78. annual meeting of the American Society of Biological Chemists conference, Philadelphia, PA, USA, 7 Jun 1987
Country of Publication:
United States
Language:
English

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