Abstract |
Two isozymes of ATP:L-methionine S-adenosyltransferase (MAT) were fractionated from rat Novikoff solid hepatoma. Their Km values for L-methionine and/or their inhibition constants for various L-methionine analogues were significantly different from the kinetic constants obtained for three isozymes fractionated from normal rat liver. Ki values for cycloleucine and (+/-)-2-aminobicyclo[2.1.1] hexane-2- carboxylic acid, presented for each tumor and liver isozyme, indicate that (+/-)-2-aminobicyclo[2.1.1] hexane-2- carboxylic acid was the more potent inhibitor. Dixon plots were also used to test a series of amino acid analogues [ cycloleucine, 1-aminocyclobutanecarboxylic acid, 1-aminocyclohexanecarboxylic acid, (+/-)-2-aminobicyclo[2.1.1] hexane-2- carboxylic acid, L-2-amino-4-hexynoic acid, (Z)-L-2-amino-5-chloro-trans-4-hexenoic acid, L- ethionine, S-n-propyl-DL- homocysteine, S-n-butyl-DL- homocysteine, and seleno-DL- ethionine] of methionine for inhibitory potency. Fixed L-methionine concentrations were used to determine the concentration of inhibitor necessary to inhibit the MAT reaction by 50%. Differential inhibitory activities of the amino acid analogues were noted between the tumor and rat liver isozymes thus supporting the suggestion that tumor-derived MAT isozymes may provide an exploitable target for cancer chemotherapy.
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Authors | J B Lombardini, J R Sufrin |
Journal | Biochemical pharmacology
(Biochem Pharmacol)
Vol. 32
Issue 3
Pg. 489-95
(Feb 01 1983)
ISSN: 0006-2952 [Print] England |
PMID | 6847699
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Isoenzymes
- Methionine
- Transferases
- Methionine Adenosyltransferase
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Topics |
- Animals
- Antineoplastic Agents
- Female
- Isoenzymes
(antagonists & inhibitors)
- Kinetics
- Liver
(enzymology)
- Liver Neoplasms, Experimental
(enzymology)
- Methionine
(analogs & derivatives, pharmacology)
- Methionine Adenosyltransferase
(antagonists & inhibitors)
- Rats
- Rats, Inbred Strains
- Transferases
(antagonists & inhibitors)
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