P5C as an Interface of Proline Interconvertible Amino Acids and Its Role in Regulation of Cell Survival and Apoptosis.
P5C as an Interface of Proline Interconvertible Amino Acids and Its Role in Regulation of Cell Survival and Apoptosis.
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DOI：
10.3390/ijms222111763
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发表时间：
2021-10-29
影响因子：
5.6
通讯作者：
Surazynski A
中科院分区：
文献类型：
--
作者：
Chalecka M;Kazberuk A;Palka J;Surazynski A
癌症代谢的研究主要集中在能量的产生和细胞周期之间碳的相互转化上。最近，氨基酸代谢，特别是非必需氨基酸（NEAAs），已被研究，强调其调节作用。细胞内能量产生和碳相互转化的重要介质之一是Δ1-pyrroline-5-carboxylate （P5C）——脯氨酸、鸟氨酸和谷氨酸相互转化的生理细胞内中间体。作为这些转化的中心组成部分，它连接三羧酸循环（TCA），尿素循环（UC）和脯氨酸循环（PC）。P5C具有含叔氮原子(N)的环状结构，与开链形式的l -谷氨酸-γ-半醛（GSAL）处于互变异构平衡。P5C由谷氨酸合成P5C合成酶（P5CS）产生，鸟氨酸通过鸟氨酸δ-氨基酸转移酶（δOAT）产生。它也可以通过P5C脱氢酶（P5CDH）转化为谷氨酸。P5C既是脯氨酸的直接前体，也是脯氨酸降解的产物。P5C转化为脯氨酸由P5C还原酶（PYCR）催化，而脯氨酸转化为P5C由脯氨酸脱氢酶/氧化酶（PRODH/POX）催化。p5c -脯氨酸- p5c相互转化形成功能性氧化还原偶。它们的转化伴随着还原氧化电位的转移，影响NADP+/NADPH比率和各种各样的过程，例如，磷酸核糖基焦磷酸（PRPP）的合成和嘌呤核糖核苷酸，这对DNA合成至关重要。本文综述了P5C作为脯氨酸、谷氨酸和鸟氨酸的相互转化介质在细胞中的代谢及其在生存和死亡调节中的作用，并特别强调了代谢背景。
Studies of cancer metabolism have focused on the production of energy and the interconversion of carbons between cell cycles. More recently, amino acid metabolism, especially non-essential amino acids (NEAAs), has been investigated, underlining their regulatory role. One of the important mediators in energy production and interconversion of carbons in the cell is Δ1-pyrroline-5-carboxylate (P5C)—the physiological intracellular intermediate of the interconversion of proline, ornithine, and glutamate. As a central component of these conversions, it links the tricarboxylic acid cycle (TCA), urea cycle (UC), and proline cycle (PC). P5C has a cyclic structure containing a tertiary nitrogen atom (N) and is in tautomeric equilibrium with the open-chain form of L-glutamate-γ-semialdehyde (GSAL). P5C is produced by P5C synthase (P5CS) from glutamate, and ornithine via ornithine δ-amino acid transferase (δOAT). It can also be converted to glutamate by P5C dehydrogenase (P5CDH). P5C is both a direct precursor of proline and a product of its degradation. The conversion of P5C to proline is catalyzed by P5C reductase (PYCR), while proline to P5C by proline dehydrogenase/oxidase (PRODH/POX). P5C-proline-P5C interconversion forms a functional redox couple. Their transformations are accompanied by the transfer of a reducing-oxidizing potential, that affect the NADP+/NADPH ratio and a wide variety of processes, e.g., the synthesis of phosphoribosyl pyrophosphate (PRPP), and purine ribonucleotides, which are crucial for DNA synthesis. This review focuses on the metabolism of P5C in the cell as an interconversion mediator of proline, glutamate, and ornithine and its role in the regulation of survival and death with particular emphasis on the metabolic context.
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影响因子：
9.8
作者：
FLEMING, GA;HAGEDORN, CH;PHANG, JM
通讯作者：
PHANG, JM
影响因子：
3.5
作者：
Du J;Zhu S;Lim RR;Chao JR
通讯作者：
Chao JR
脯氨酸代谢在癌症中的作用。
影响因子：
7
作者：
Burke L;Guterman I;Palacios Gallego R;Britton RG;Burschowsky D;Tufarelli C;Rufini A
通讯作者：
Rufini A
影响因子：
16.6
作者：
Elia I;Broekaert D;Christen S;Boon R;Radaelli E;Orth MF;Verfaillie C;Grünewald TGP;Fendt SM
通讯作者：
Fendt SM
影响因子：
3.7
作者：
De Ingeniis J;Ratnikov B;Richardson AD;Scott DA;Aza-Blanc P;De SK;Kazanov M;Pellecchia M;Ronai Z;Osterman AL;Smith JW
通讯作者：
Smith JW