Liver Zn-thionein (ZnMT) regulates the interaction of Zn and Pb with delta-aminolevulinic acid dehydratase (ALAD)
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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59 BASIC BIOLOGICAL SCIENCES
CARBON-OXYGEN LYASES
ENZYME ACTIVITY
LEAD
BIOLOGICAL EFFECTS
ZINC
BIOCHEMICAL REACTION KINETICS
CATTLE
INHIBITION
ION EXCHANGE CHROMATOGRAPHY
LEAD 203
LIVER
METALLOTHIONEIN
RATS
TRACER TECHNIQUES
ZINC 65
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BODY
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DOMESTIC ANIMALS
ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
ENZYMES
EVEN-ODD NUCLEI
GLANDS
HEAVY NUCLEI
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LEAD ISOTOPES
LYASES
MAMMALS
METALLOPROTEINS
METALS
NUCLEI
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RODENTS
RUMINANTS
SECONDS LIVING RADIOISOTOPES
SEPARATION PROCESSES
VERTEBRATES
ZINC ISOTOPES
560300* - Chemicals Metabolism & Toxicology
550501 - Metabolism- Tracer Techniques