INACTIVATION AND DISSOCIATION OF S-ADENOSYLMETHIONINE SYNTHETASE BY MODIFICATION OF SULFHYDRYL-GROUPS AND ITS POSSIBLE OCCURRENCE IN CIRRHOSIS

被引:47
作者
CORRALES, F
CABRERO, C
PAJARES, MA
ORTIZ, P
MARTINDUCE, A
MATO, JM
机构
[1] FDN JIMENEZ DIAZ,REYES CATOLICOS 2,E-28040 MADRID,SPAIN
[2] HOSP ALCALA HENARES,SERV CIRUGIA DIGEST,MADRID,SPAIN
[3] CSIC,INST BIOMED,MADRID 6,SPAIN
关键词
D O I
10.1002/hep.1840110210
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Catalytically active human and rat liver S‐adenosylmethionine synthetase exists mainly in tetramer and dimer form. In liver biopsy samples from cirrhotic patients a marked reduction in total S‐adenosylmethionine synthetase activity and a specific loss of the tetrameric form of the enzyme exist. We have investigated the possible role of sulfhydryl groups in maintaining the structure and activity of S‐adenosylmethionine synthetase. Both forms of S‐adenosylmethionine synthetase are rapidly inactivated by N‐ethylmaleimide, and the loss of enzyme activity correlates with the incorporation of approximately 2 moles N‐ethylmaleimide per mole of subunit. In addition, reaction with N‐ethylmaleimide resulted in displacement of the tetramer‐dimer equilibrium of the enzyme toward the dimer, but no monomer was detected under these conditions. A catalytically active monomeric S‐adenosylmethionine synthetase was detected in the cytosolic extract from a liver biopsy sample from a cirrhotic patient, supporting our model for the structure of S‐adenosylmethionine synthetase. Because treatment of S‐adenosylmethionine synthetase with N‐ethylmaleimide resembles the situation of this enzyme in cirrhotic patients, it is proposed that impaired protection of the enzyme from oxidizing agents caused by a decreased synthesis of glutathione can explain the diminished synthesis of S‐adenosylmethionine in liver cirrhosis. Copyright © 1990 American Association for the Study of Liver Diseases
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页码:216 / 222
页数:7
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