SYNTHESIS OF MULTIMETHYL-BRANCHED FATTY-ACIDS BY AVIAN AND MAMMALIAN FATTY-ACID SYNTHETASE AND ITS REGULATION BY MALONYL-COA DECARBOXYLASE IN UROPYGIAL GLAND
SYNTHESIS OF MULTIMETHYL-BRANCHED FATTY-ACIDS BY AVIAN AND MAMMALIAN FATTY-ACID SYNTHETASE AND ITS REGULATION BY MALONYL-COA DECARBOXYLASE IN UROPYGIAL GLAND
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DOI：
10.1016/0003-9861(78)90474-5
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发表时间：
1978-01-01
影响因子：
3.9
通讯作者：
ROGERS, L
中科院分区：
文献类型：
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作者：
BUCKNER, JS;KOLATTUKUDY, PE;ROGERS, L
鹅肝脂肪酸合酶经Sepharose4B凝胶过滤部分纯化后，甲基丙二酰辅酶A的相对掺入速率(相对于丙二酰辅酶A)与纯化后的尿囊腺脂肪酸合酶的相对参入率相同。在乙酰辅酶A存在下，2，4，6，8-四甲基十二酸和2，4，6，8，10-五甲基十二酸两种来源的酶主要结合甲基丙二酰辅酶A。甲基丙二酰辅酶A是腺体酶的丙二酰辅酶A的竞争性抑制物，就像以前观察到的其他动物的脂肪酸合成酶一样。针对腺酶制备的兔抗血清与肝酶发生交叉反应，Ouchterlony双扩散分析显示免疫沉淀线完全融合。该抗血清可抑制肝脏和尿囊腺合成酶催化的n-脂肪酸和支链脂肪酸的合成。这些结果表明，这两种组织的合成酶可能是相同的，支链脂肪酸和n-脂肪酸是由同一种酶合成的。对从鹅各种器官制备的105,000克上清液的免疫学检测表明，只有尾咽腺含有一种与从该腺提纯的丙二酰辅酶A脱羧酶抗体发生交叉反应的蛋白。腺体中的脂肪酸合成酶合成多甲基分支脂肪酸的原因是，在这个器官中，组织特异性和底物特异性的脱羧酶只能使合成酶获得甲基丙二酰辅酶A。从大鼠乳腺和肝脏中部分纯化的脂肪酸合成酶还催化[甲基-14C]甲基丙二酰辅酶A分别以乙酰辅酶A和丙酰辅酶A为引发物合成2，4，6，8-四甲基十一酸和2，4，6，8-四甲基十一酸。有证据表明，在丙二酰辅酶A或其他n-脂肪酸前体的存在下，老鼠和鹅的脂肪酸合成酶可以从甲基丙二酰辅酶A中产生含有直链和分支区的脂肪酸。在导致甲基丙二酰辅酶A积聚的病理条件下，脂肪酸合成酶可能会产生异常的支链酸。
Fatty acid synthetase, partially purified by gel filtration with Sepharose 4B from goose liver, showed the same relative rate of incorporation of methylmalonyl-CoA (compared to malonyl-CoA) as that observed with the purified fatty acid synthetase from the uropygial gland. In the presence of acetyl-CoA, methylmalonyl-CoA was incorporated mainly into 2,4,6,8-tetramethyldecanoic acid and 2,4,6,8,10-pentamethyldodecanoic acid by the enzyme from both sources. Methylmalonyl-CoA was a competitive inhibitor with respect to malonyl-CoA for the enzyme from the gland just as previously observed for fatty acid synthetase from other animals. Rabbit antiserum prepared against the gland enzyme cross-reacted with the liver enzyme, and Ouchterlony double-diffusion analyses showed complete fusion of the immunoprecipitant lines. The antiserum inhibited both the synthesis of n-fatty acids and branched fatty acids catalyzed by the synthetases from both liver and the uropygial gland. These results suggest that the synthetases from the two tissues may be identical and that branched and n-fatty acids are synthesized by the same enzyme. Immunological examination of the 105,000 g supernatant prepared from a variety of organs from the goose showed that only the uropygial gland contained a protein which cross-reacted with the antiserum prepared against malonyl-CoA decarboxylase purified from the gland. The reason for the synthesis of multimethyl-branched fatty acids by the fatty acid synthetase in the gland is that in this organ the tissue-specific and substrate-specific decarboxylase makes only methylmalonyl-CoA available to the synthetase. Fatty acid synthetase, partially purified from the mammary gland and the liver of rats, also catalyzed incorporation of [methyl-14C]methymalonyl-CoA into 2,4,6,8-tetramethyldecanoic acid and 2,4,6,8-tetramethylundecanoic acid with acetyl-CoA and propionyl-CoA, respectively, as the primers. Evidence suggests fatty acids containing straight and branched regions can be generated by the fatty acid synthetase from the rat and goose, from methylmalonyl-CoA in the presence of malonyl-CoA or other precursors of n-fatty acids. Under the pathological conditions which result in accumulation of methylmalonyl-CoA, abnormal branched acids may be generated by the fatty acid synthetase.