The metabolism of proline as microenvironmental stress substrate.
The metabolism of proline as microenvironmental stress substrate.
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DOI：
10.1093/jn/138.10.2008s
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Liu Y
中科院分区：
文献类型：
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作者：
Phang JM;Pandhare J;Liu Y
脯氨酸是一种独特的蛋白质类次生氨基酸，具有独特的代谢系统。最近的发现定义了这一系统的调节，这导致我们提出，在炎症和肿瘤发生的微环境中，脯氨酸是一种应激底物。作为胁迫底物的标准是：1)利用脯氨酸的酶对胁迫信号作出反应，2)有大量的可动员的Pro库，3)Pro的代谢具有特殊的胁迫功能。研究表明，Pro利用酶，即Pro氧化酶/Pro脱氢酶，对遗传毒性、炎症和营养胁迫作出反应。细胞外基质、结缔组织和骨骼中以胶原的形式储存着作为底物的脯氨酸，在基质金属蛋白酶、多肽酶和脯氨酸酶的顺序作用下迅速从这个储存库中释放出来。其特殊的功能包括通过Pro氧化酶/Pro脱氢酶利用Pro产生超氧阴离子自由基，通过内源和外源途径启动细胞凋亡。在营养胁迫条件下，脯氨酸是一种能量来源。它为三羧酸循环提供碳，也参与脯氨酸循环。后者由线粒体脯氨酸氧化酶和胞质吡咯烷-5-羧酸还原酶催化，将磷酸戊糖途径的还原电位送入线粒体，生成ATP和氧化电位，激活胞质磷酸戊糖途径。
Proline, a unique proteogenic secondary amino acid, has its own metabolic system with special features. Recent findings defining the regulation of this system led us to propose that proline is a stress substrate in the microenvironment of inflammation and tumorigenesis. The criteria for proline as a stress substrate are: 1) the enzymes utilizing proline respond to stress signaling, 2) there is a large, mobilizable pool of proline and 3) the metabolism of proline serves special stress functions. Studies show that the proline utilizing enzyme, proline oxidase/proline dehydrogenase responds to genotoxic, inflammatory and nutrient stress. Proline as substrate is stored as collagen in extracellular matrix, connective tissue and bone, and it is rapidly released from this reservoir by the sequential action of matrix metalloproteinases, peptidases and prolidase. Special functions include the use of proline by proline oxidase/proline dehydrogenase to generate superoxide radicals which initiate apoptosis by intrinsic and extrinsic pathways. Under conditions of nutrient stress, proline is an energy source. It provides carbons for the tricarboxylic acid cycle and, also participates in the proline cycle. The latter, catalyzed by mitochondrial proline oxidase and cytosolic pyrroline-5-carboxylate reductase, shuttles reducing potential from the pentose phosphate pathway into mitochondria to generate ATP and oxidizing potential to activate the cytosolic pentose phosphate pathway.