Inhibition of erythrocyte 5-aminolaevulinate hydrolase activity by tin and its prevention by selenite.
Mice were injected with either SnCl2 (intraperitoneal) or Na2SeO3 (subcutaneous) alone or together at doses of 50 mumol/kg body weight. After 20 hours blood was collected and the concentrations of tin (Sn) and Selenium (Se) and the activity of 5-aminolaevulinate hydrolyase (ALA dehydratase, EC 4.2.1.24) in blood were determined. The concentrations of Sn in whole blood were 4.9 (SD 1.5) nmol/ml (n = 4) and ALA dehydratase activity was 10% of the control in Sn treated animals. Concentrations of Sn were 2.6 (SD 0.6) nmol/ml and ALA dehydratase activity was 92% of that in control animals when Sn and Se were simultaneously injected. The supernatant from lysed erythrocytes from Sn treated mice were applied to a Sephacryl S-300 column. The predominant peak containing Sn was eluted at the position of haemoglobin; a second peak was eluted at the position of ALA dehydratase. When the supernatant of lysed erythrocytes from mice injected with Sn and Se was chromatographed, a negligible amount of Sn was detected in the ALA dehydratase fraction. It thus appears that Sn binds to ALA dehydratase molecules and inhibits enzyme activity, and that simultaneous injection of Se prevents Sn binding to ALA dehydratase, thereby preventing the inhibition of ALA dehydratase activity by Sn.
Chiba
M
M
Department of Hygiene, Juntendo University School of Medicine, Tokyo, Japan.
Shinohara
A
A
D000818:Animals; D001665:Binding Sites; D002850:Chromatography, Gel; D003864:Depression, Chemical; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors*; D012643:Selenium / Q000378:metabolism* / Q000494:pharmacology; D018038:Sodium Selenite; D014001:Tin / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D017971:Tin Compounds
D017971:Tin Compounds; C023599:stannous chloride; D014001:Tin; D000623:Porphobilinogen Synthase; D012643:Selenium; D018038:Sodium Selenite