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Biomedical subjects

Y Kidani

Publications and source records attributed to Y Kidani.

69 records · Page 4Linked to original sources

Coordination chemical studies on metalloenzymes. II. Kinetic behavior of various types of chelating agents towards bovine carbonic anhydrase.

In order to investigate the kinetics and mechanism of the removal of zinc ions from bovine carbonic anhydrase [EC 4.2.1.1] (BCA), several chelating agents with various stability constants were used to remove zinc from BCA. The second-order rate constants (kaap) of zinc removal from BCA were found to be in the following order; 2,6-pyridinedicarboxylic acid greater than 2-pyridinecarboxylic acid greater than 2,4-pyridinedicarboxylic acid greater than 2,3-pyridinedicarboxylic acid greater than or approximately 1,10-phenanthroline greater than or approximately 5-methyl-1,10-phenanthroline greater than 2,2'-bipyridine. With similar chelating agents the greater the stability constant, the faster was the rate of removal of zinc ions from BCA. With EDTA, trans-1,2-cyclohexanediaminetetraacetic acid, and nitrilotriacetic acid, the rate of zinc ion removal from the native enzyme was governed by the rate of spontaneous dissociation of zinc enzyme. The rate constants for the removal of zinc ions from BCA were governed by the affinity of the chelating agents for the metal ion and the conformation of the chelating agents. Based on these findings, reaction pathways for various chelating agents are proposed.

Animals↗

Coordination chemical studies on metalloenzymes. Kinetics and mechanism of the Zn(II) exchange reaction between chelating agent and apo-bovine carbonic anhydrase.

The mechanism of removal of the zinc ion from bovine carbonic anhydrase [EC 4.2.1.1] (BCA) by a chelating agent was studied. It was shown that the removal of the zinc ion from BCA took place through the formation of a ternary complex involving the enzyme, chelating agent, and metal ions. The formation constant of the ternary complex (KEML) was 10(2) M-1. This value was lower than the formation constant assumed by Wilkins. The reaction of zinc-2, 6-pyridinedicarboxylate complex with the apoenzyme also took place through the formation of the ternary complex and the species which reacted with apo-BCA was a 1:1 complex of zinc and 2, 6-pyridine-dicarboxylate. The theoretical equilibrium equation derived from the reaction mechanism showed a good fit with observed equilibrium dialysis data.

Animals↗

Antitumor effects of a new lipophilic platinum compound, trans-bis(n-valerato)(1R,2R-cyclohexanediamine)(oxalato)platinum(IV), in mice.

A new lipophilic platinum (Pt) compound, trans-bis(n-valerato)(1R,2R-cyclohexanediamine)(oxalato)Pt(lV) (C5-OHP), was compared with cisplatin (CDDP) by intraperitoneal injection for antitumor activities against 3 different mouse models, L1210 leukemia, LMFS sarcoma with high metastatic potential and spontaneous mammary tumor. C5-OHP cured both CDDP-sensitive and -resistant L1210 leukemia frequently. CDDP did not cure the leukemia, although it prolonged the survival of diseased mice significantly. C5-OHP cured early and advanced LMFS sarcomas more frequently than CDDP. Cured mice had acquired antitumor immunity, indicating the pivotal role of the immune system in induction of the cure of tumors. It is likely tllat C5-OHP can eradicate tumor cells more effectively than CDDP by virtue of its weaker suppressive effects on the immune system. C5-OHP but not CDDP could cure mammary tumors. C5-OHP manifested a curative effect against LMFS tumors by oral route. These results indicate that C5-OHP is a promising anticancer agent worthy of clinical trial.

Animals↗