Binding of cadmium to alcohol dehydrogenase in the liver before induction of metallothionein.
The cadmium-binding protein (Cd-BP) with the highest affinity to Cd other than metallothionein (MT) is assumed to be the target molecule for the toxicity of Cd and one of the major zinc (Zn)-containing proteins in the liver supernatant of rats has been identified as the Cd-BP before induction of MT. In the present study the Zn-containing Cd-BP was assumed to be alcohol dehydrogenase (ADH) from the similarity in several characteristic properties such as molecular size, isoelectric point, Zn content and enzyme activity. Zn bound to non-active site in ADH was replaced with Cd both in vivo and in vitro. Cd bound to ADH to an extent more than the replacement in vitro and the enzyme activity was decreased in vitro by Cd. However, the ADH enzyme activity was not affected in vivo despite the replacement of Zn with Cd and binding of Cd to ADH. This difference was explained by the weaker affinity of Cd to the active site than the other binding sites for Cd in other high molecular weight proteins. The result also suggested that ADH sequesters Cd temporally before induction of MT and reduces the toxicity of Cd without being affected its enzyme activity and that the target molecules for the toxicity are other Cd-BPs.
Suzuki
K T
KT
National Institute for Environmental Studies, Ibaraki, Japan.
Sunaga
H
H
Yamane
Y
Y
Aoki
Y
Y
D000426:Alcohol Dehydrogenase / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D002104:Cadmium / Q000378:metabolism*; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D007526:Isoelectric Point; D008099:Liver / Q000737:chemistry*; D008668:Metallothionein / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000633:toxicity; D008970:Molecular Weight; D051381:Rats; D011919:Rats, Inbred Strains; D013053:Spectrophotometry; D015032:Zinc / Q000032:analysis / Q000378:metabolism
C004203:cadmium-binding protein; D002104:Cadmium; D008668:Metallothionein; D000426:Alcohol Dehydrogenase; D015032:Zinc