MECHANISM OF ACTION OF CERULENIN ON FATTY-ACID SYNTHETASE - EFFECT OF CERULENIN ON IODOACETAMIDE-INDUCED MALONYL-COA DECARBOXYLASE ACTIVITY
MECHANISM OF ACTION OF CERULENIN ON FATTY-ACID SYNTHETASE - EFFECT OF CERULENIN ON IODOACETAMIDE-INDUCED MALONYL-COA DECARBOXYLASE ACTIVITY
复制标题
DOI：
10.1093/oxfordjournals.jbchem.a133933
复制
发表时间：
1982-01-01
影响因子：
2.7
通讯作者：
OKUDA, S
中科院分区：
文献类型：
--
作者：
KAWAGUCHI, A;TOMODA, H;OKUDA, S
浅蓝菌素是一种具有（2 R）（3S）-2，3-环氧-4-氧代-7，10-十二碳二烯酰胺结构的抗生素，可不可逆地灭活酵母脂肪酸合成酶。在合成酶的所有催化活性中，只有缩合反应被浅蓝菌素抑制。在0.5度。C和pH 6.5时，二级速率常数k = 88 M-1·cm-1。s-1是浅蓝菌素灭活的产物。这个值是. apprx。90-比碘乙酰胺使酶失活的速率常数大一倍。通过用乙酰辅酶A而不是丙二酰辅酶A预先处理来保护酶免受浅蓝菌素的作用。用碘乙酰胺处理酶，同时损害合成酶活性，诱导丙二酰辅酶A脱羧酶活性。浅蓝菌素对碘乙酰胺处理的酶的丙二酰辅酶A脱羧酶活性没有影响。N-乙基马来酰亚胺抑制碘乙酰胺诱导的丙二酰辅酶A脱羧酶活性。当酶与浅蓝菌素预孵育时，即使用碘乙酰胺处理酶后也不能检测到丙二酰辅酶A脱羧酶活性。因此，浅蓝菌素与合成酶的外周SH-基团的反应是导致失活的原因。
Cerulenin, an antibiotic with the structure of (2R)(3S)-2,3-epxoy-4-oxo-7,10-dodecadienoylamide, irreversibly inactivates yeast fatty acid synthetase. Of all catalytic activities of the synthetase, only the condensation reaction is inhibited by cerulenin. At 0.degree. C and pH 6.5, the 2nd-order rate constant of k = 88 M-1 .cntdot. s-1 was obtained for the inactivation by cerulenin. This value was .apprx. 90-times greater than the rate constant for the inactivation of the enzyme by iodoacetamide. The enzyme was protected against the action of cerulenin by prior treatment with acetyl-CoA but not malonyl-CoA. Treatment of the enzyme with iodoacetamide, while impairing the synthetase activity, induced malonyl-CoA decarboxylase activity. Cerulenin had no effect on the malonyl-CoA decarboxylase activity of the iodoacetamide-treated enzyme. N-ethylmaleimide inhibited the iodoacetamide-induced malonyl-CoA decarboxylase activity. When the enzyme was preincubated with cerulenin, malonyl-CoA decarboxylase activity could not be detected even after treatment of the enzyme with iodoacetamide. Thus, the reaction of cerulenin with the peripheral SH-groups of the synthetase is responsible for the inactivation.