Correlation of isozyme patterns of S-adenosylmethionine synthetase with fetal stages and pathological states of the liver
Liau, M.C.; Chang, C.F.; Belanger, L.; Grenier, A.
Cancer Research 39(1): 162-169
1979
ISSN/ISBN: 0008-5472 PMID: 761186 Document Number: 147488
The liver is the most active organ engaged in S-adenosylmethionine metabolism. S-Adenosylmethionine synthetase isozymes (EC 2.5.1.6) were studied in normal, fetal and pathological livers including hepatoma to correlate their activities with developmental stages and pathophysiological states of the liver. Three isozymes of S-adenosylmethionine synthetase, namely low, intermediate and high-Km, were identified from adult rat and human livers. The Km (methionine) are 3.6 .mu.M, 23 .mu.M and 1.03 mM for the rat liver isozymes and 3.1 .mu.M, 20 .mu.M and 0.65 mM for the human liver isozymes. The high Km isozyme could be distinguished from other isozymes by its dependency on sulfhydryl reagents, activation by dimethyl sulfoxide and chromatographic behaviors on Sepharose 6B and DEAE-cellulose columns. The activity of the low Km isozyme and to a lesser extent that of the intermediate-Km isozyme was greatly enhanced in livers characteristic of rapid growth, such as in fetal, newborn and regenerating livers. The activity of the high-Km isozyme was undetectable in fetal livers and was greatly reduced during the growth phase of remnant liver following partial hepatectomy. Only the intermediate Km isozyme was detectable in rat Novikoff hepatoma, indicating a unique metabolic feature associated with this tumor with respect to isozymes of S-adenosylmethionine synthetase. Such an aberration may have significant bearing on liver neoplasia. Livers of patients who died of hereditary tyrosinemia showed abnormal isozyme patterns of S-adenosylmethionine synthetase. The high-Km isozyme was either undetectable, thus resembling the fetal pattern, or present in a relatively low amount. Abnormal development of S-adenosylmethionine synthetase isozymes may be partly responsible for abnormal methionine metabolism and hepatic dysfunctions often associated with these patients.