P5C as an Interface of Proline Interconvertible Amino Acids and Its Role in Regulation of Cell Survival and Apoptosis

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 i...

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Autores principales:	Magda Chalecka, Adam Kazberuk, Jerzy Palka, Arkadiusz Surazynski
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Δ<sup>1</sup>-pyrroline-5-carboxylate proline cycle redox signaling P5C synthase P5C dehydrogenase P5C reductase Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/1ed2ab36b8ed4716a27ce9e0c6d978f8
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spelling	oai:doaj.org-article:1ed2ab36b8ed4716a27ce9e0c6d978f82021-11-11T17:12:51ZP5C as an Interface of Proline Interconvertible Amino Acids and Its Role in Regulation of Cell Survival and Apoptosis10.3390/ijms2221117631422-00671661-6596https://doaj.org/article/1ed2ab36b8ed4716a27ce9e0c6d978f82021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11763https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Studies 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 Δ<sup>1</sup>-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-<i>γ</i>-semialdehyde (GSAL). P5C is produced by P5C synthase (P5CS) from glutamate, and ornithine via ornithine <i>δ</i>-amino acid transferase (<i>δ</i>OAT). 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.Magda ChaleckaAdam KazberukJerzy PalkaArkadiusz SurazynskiMDPI AGarticleΔ<sup>1</sup>-pyrroline-5-carboxylateproline cycleredox signalingP5C synthaseP5C dehydrogenaseP5C reductaseBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11763, p 11763 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Δ<sup>1</sup>-pyrroline-5-carboxylate proline cycle redox signaling P5C synthase P5C dehydrogenase P5C reductase Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Δ<sup>1</sup>-pyrroline-5-carboxylate proline cycle redox signaling P5C synthase P5C dehydrogenase P5C reductase Biology (General) QH301-705.5 Chemistry QD1-999 Magda Chalecka Adam Kazberuk Jerzy Palka Arkadiusz Surazynski P5C as an Interface of Proline Interconvertible Amino Acids and Its Role in Regulation of Cell Survival and Apoptosis
description	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 Δ<sup>1</sup>-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-<i>γ</i>-semialdehyde (GSAL). P5C is produced by P5C synthase (P5CS) from glutamate, and ornithine via ornithine <i>δ</i>-amino acid transferase (<i>δ</i>OAT). 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.
format	article
author	Magda Chalecka Adam Kazberuk Jerzy Palka Arkadiusz Surazynski
author_facet	Magda Chalecka Adam Kazberuk Jerzy Palka Arkadiusz Surazynski
author_sort	Magda Chalecka
title	P5C as an Interface of Proline Interconvertible Amino Acids and Its Role in Regulation of Cell Survival and Apoptosis
title_short	P5C as an Interface of Proline Interconvertible Amino Acids and Its Role in Regulation of Cell Survival and Apoptosis
title_full	P5C as an Interface of Proline Interconvertible Amino Acids and Its Role in Regulation of Cell Survival and Apoptosis
title_fullStr	P5C as an Interface of Proline Interconvertible Amino Acids and Its Role in Regulation of Cell Survival and Apoptosis
title_full_unstemmed	P5C as an Interface of Proline Interconvertible Amino Acids and Its Role in Regulation of Cell Survival and Apoptosis
title_sort	p5c as an interface of proline interconvertible amino acids and its role in regulation of cell survival and apoptosis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1ed2ab36b8ed4716a27ce9e0c6d978f8
work_keys_str_mv	AT magdachalecka p5casaninterfaceofprolineinterconvertibleaminoacidsanditsroleinregulationofcellsurvivalandapoptosis AT adamkazberuk p5casaninterfaceofprolineinterconvertibleaminoacidsanditsroleinregulationofcellsurvivalandapoptosis AT jerzypalka p5casaninterfaceofprolineinterconvertibleaminoacidsanditsroleinregulationofcellsurvivalandapoptosis AT arkadiuszsurazynski p5casaninterfaceofprolineinterconvertibleaminoacidsanditsroleinregulationofcellsurvivalandapoptosis
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P5C as an Interface of Proline Interconvertible Amino Acids and Its Role in Regulation of Cell Survival and Apoptosis

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