Branched Chain Amino Acid Transaminase Isozymes and Cellular Differentiation and Carcinogenesis

概要

論文の詳細を見る
Branched chain amino acid transaminase (EC 2.6. 1.6) can be separated in to 3 types (enzyme I-III) by DEAE cellulose column chromatography or polyacrylamide disc gel eletrophoresis. Enzyme I is ubiquitously distributed in various tissues of rats, while enzymes II and III are found only in liver and brain, respectively. Enzymes I and III are very similar in their properties and are active for all three amino acids (valine, leucine and isoleucine), while enzyme II is active only for leucine and its Km is very high (25 mM). These isozymes are, however, distinguishable immunochemically. They are, enzyme II in particular, inducible in rats by various physiological conditions, and change of their activities coincides well with the amount of ketone body formed from leucine. These findings shows that transamination is a rate limiting step of leucine metabolism.<BR>In fetal rat liver only enzyme I is present and enzyme II appears rapidly after birth. Regenerating liver has essentially the same isozyme pattern as normal adult liver, and in neither has enzyme III yet been detected. Various Yoshida ascites hepatomas, which are poorly differentiated, contain enzymes I and III, but not enzyme II. The enzyme III in hepatoma (AH 130) is indistinguishable from that found in normal brain, both enzymologically and immunochemically. Various Morris hepatomas show a variety of isozyme patterns; enzyme I only (fetal pattern), enzymes I and II (normal pattern) or a mixture of all three isozymes, but not the pattern found in Yoshida ascites hepatomas. There is no definite correlation between the isozyme pattern and rate of tumor growth. Primary hepatomas induced by 3'-methyl DAB also contain enzymes I and X and benign adenomas show the normal isozyme pattern. These findings suggest that the appearance of enzyme III may be due to aberration of gene expression caused by carcinogenesis. An alternative explanation is that it is simply due to selection of a cell population. To test this possibility we examined cultured rat hepatocytes before and after their transformation by chemical carcinogens. A cell line isolated and cloned from liver of a 5 day old rat, contains only enzyme I, but after transformation by either 4-NQO or DAB, the cells acquired both enzyme X and tumorigenicity. Among 12 other cell lines examined only those showing great deviation from euploid chromosomal numbers contained enzyme III. These results indicate that the appearance of enzyme III is indeed due to aberration of gene expression and that these isozymes may be very suitable markers of cellular differentiation and dedifferentiation as follows:<BR>_??_
Japan Society of Clinical Chemistryの論文

Branched Chain Amino Acid Transaminase Isozymes and Cellular Differentiation and Carcinogenesis

スポンサーリンク

概要

著者

関連論文

スポンサーリンク