The entire pathway of palmitate synthesis from malonyl-CoA in mammals is catalyzed by a single, homodimeric, multifunctional protein, the fatty acid synthase. Each subunit contains three N-terminal domains, the beta-ketoacyl synthase, malonyl/acetyl transferase and dehydrase separated by a structural core from four C-terminal domains, the enoyl reductase, beta-ketoacyl reductase, acyl carrier protein and thiosterase. The kinetics and specificities of the substrate loading reaction catalyzed by the malonyl/acetyl transferase, the condensation reaction catalyzed by beta-ketoacyl synthase and chain-terminating reaction catalyzed by the thioesterase ensure that intermediates do not leak off the enzyme, saturated chains exclusively are elongated and palmitate is released as the major product. Only in the fatty acid synthase dimer do the subunits adopt conformations that facilitate productive coupling of the individual reactions for fatty acid synthesis at the two acyl carrier protein centers. Introduction of a double tagging and dual affinity chromatographic procedure has permitted the engineering and isolation of heterodimeric fatty acid synthases carrying different mutations on each subunit. Characterization of these heterodimers, by activity assays and chemical cross-linking, has been exploited to map the functional topology of the protein. The results reveal that the two acyl carrier protein domains engage in substrate loading and condensation reactions catalyzed by the malonyl/acetyl transferase and beta-ketoacyl synthase domains of either subunit. In contrast, the reactions involved in processing of the beta-carbon atom, following each chain elongation step, together with the release of palmitate, are catalyzed by the cooperation of the acyl carrier protein with catalytic domains of the same subunit. These findings suggest a revised model for the fatty acid synthase in which the two polypeptides are oriented such that head-to-tail contacts are formed both between and within subunits.

中文翻译：

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动物脂肪酸合酶的结构和功能组织。

在哺乳动物中，由丙二酰辅酶A合成棕榈酸酯的整个途径是由单一的同型二聚体，多功能蛋白即脂肪酸合酶催化的。每个亚基包含三个N末端结构域，β-酮酰基合酶，丙二酰/乙酰基转移酶和脱水酶，结构核心将其与四个C末端结构域分开，分别是烯酰基还原酶，β-酮酰基还原酶，酰基载体蛋白和硫酯酶。丙二酰/乙酰基转移酶催化的底物负载反应的动力学和特异性，β-酮酰基合酶催化的缩合反应和硫酯酶催化的链终止反应确保了中间体不会从酶中泄漏出来，饱和链只被延长棕榈酸酯是主要产品。只有在脂肪酸合酶二聚体中，亚基才采用促进在两个酰基载体蛋白中心进行脂肪酸合成的各个反应的有效偶联的构象。双标签和双亲和层析方法的引入已经允许工程化和分离在每个亚基上携带不同突变的异二聚脂肪酸合酶。通过活性分析和化学交联来表征这些异二聚体已被用来绘制蛋白质的功能拓扑图。结果表明，两个酰基载体蛋白结构域均参与任一亚基的丙二酰/乙酰基转移酶和β-酮酰基合酶域催化的底物负载和缩合反应。相比之下，参与β-碳原子加工的反应 在每个链延长步骤之后，棕榈酸酯的释放通过酰基载体蛋白与相同亚基的催化结构域的协同作用而被催化。这些发现提示了脂肪酸合酶的修正模型，其中两个多肽被定向使得在亚基之间和之内形成头尾接触。