Metabolites produced via traditional biochemical processes affect intracellular communication, inflammation, and malignancy. Unexpectedly, acetyl-CoA, α-ketoglutarate and palmitic acid, which are chemical species of reactions catalyzed by highly abundant, gigantic enzymatic complexes, dubbed as “metabolons”, have broad “nonmetabolic” signaling functions. Conserved unstructured regions within metabolons determine the yield of these metabolites. Unstructured regions tether functional protein domains, act as spatial constraints to confine constituent enzyme communication, and, in the case of acetyl-CoA production, tend to be regulated by intricate phosphorylation patterns. This review presents the multifaceted roles of these three significant metabolites and describes how their perturbation leads to altered or transformed cellular function. Their dedicated enzymatic systems are then introduced, namely, the pyruvate dehydrogenase (PDH) and oxoglutarate dehydrogenase (OGDH) complexes, and the fatty acid synthase (FAS), with a particular focus on their structural characterization and the localization of unstructured regions. Finally, upstream metabolite regulation, in which spatial occupancy of unstructured regions within dedicated metabolons may affect metabolite availability and subsequently alter cell functions, is discussed.

中文翻译：

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大型酶复合物的非结构化区域控制具有信号功能的代谢物的可用性。

通过传统生化过程产生的代谢物会影响细胞内通讯、炎症和恶性肿瘤。出乎意料的是，乙酰辅酶 A、α-酮戊二酸和棕榈酸是由高度丰富的、巨大的酶复合物催化的化学反应，被称为“代谢物”，具有广泛的“非代谢”信号传导功能。代谢物内的保守非结构化区域决定了这些代谢物的产量。非结构化区域连接功能性蛋白质结构域，作为空间约束来限制组成酶的通讯，并且在乙酰辅酶 A 产生的情况下，往往受复杂的磷酸化模式的调节。本综述介绍了这三种重要代谢物的多方面作用，并描述了它们的扰动如何导致细胞功能改变或转变。然后引入了他们的专用酶系统，即丙酮酸脱氢酶 (PDH) 和酮戊二酸脱氢酶 (OGDH) 复合物，以及脂肪酸合酶 (FAS)，特别关注它们的结构表征和非结构化区域的定位。最后，讨论了上游代谢物调节，其中专用代谢物中非结构化区域的空间占用可能会影响代谢物的可用性并随后改变细胞功能。