Abstract：
A host of metabolic enzymes reversibly self-assemble to form membrane-less, intracellular filaments under normal physiological conditions and in response to stress. Often, these enzymes reside at metabolic control points, suggesting that filament formation affords an additional regulatory mechanism. Examples include cytidine-5\'-triphosphate (CTP) synthase (CTPS), which catalyzes the rate-limiting step for the de novo biosynthesis of CTP; inosine-5\'-monophosphate dehydrogenase (IMPDH), which controls biosynthetic access to guanosine-5\'-triphosphate (GTP); and ∆1-pyrroline-5-carboxylate (P5C) synthase (P5CS) that catalyzes the formation of P5C, which links the Krebs cycle, urea cycle, and proline metabolism. Intriguingly, CTPS can exist in co-assemblies with IMPDH or P5CS. Since GTP is an allosteric activator of CTPS, the association of CTPS and IMPDH filaments accords with the need to coordinate pyrimidine and purine biosynthesis. Herein, a hypothesis is presented furnishing a biochemical connection underlying co-assembly of CTPS and P5CS filaments - potent inhibition of CTPS by glutamate γ-semialdehyde, the open-chain form of P5C.
摘要：
大量的代谢酶可逆地自我组装形成无膜，在正常生理条件下和对压力的反应。通常,这些酶位于代谢控制点，表明细丝的形成提供了额外的调节机制。实例包括胞苷-5'-三磷酸（CTP）合酶（CTPS），催化CTP从头生物合成的限速步骤；肌苷-5'-单磷酸脱氢酶（IMPDH），其控制鸟苷-5'-三磷酸（GTP）的生物合成途径；和Δ1-吡咯啉-5-羧酸（P5C）合酶（P5CS），催化P5C的形成，连接克雷布斯周期，尿素循环,和脯氨酸代谢。有趣的是，CTPS可以与IMPDH或P5CS共同组装。由于GTP是CTPS的变构激活剂,CTPS和IMPDH丝的结合符合协调嘧啶和嘌呤生物合成的需要。在这里，提出了一个假设，提供了CTPS和P5CS细丝共同组装的生化联系-谷氨酸γ-半醛对CTPS的有效抑制，P5C的开链形式。
