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Aspartate-glutamate carrier 2 (citrin): a role in glucose and amino acid metabolism in the liver
Aspartate-glutamate carrier 2 (AGC2, citrin) is a mitochondrial carrier expressed in the liver that transports aspartate from mitochondria into the cytosol in exchange for glutamate. The AGC2 is the main component of the malate-aspartate shuttle (MAS) that ensures indirect transport of NADH produced...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Korean Society for Biochemistry and Molecular Biology
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10390287/ https://www.ncbi.nlm.nih.gov/pubmed/37254569 http://dx.doi.org/10.5483/BMBRep.2023-0052 |
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author | Holeček, Milan |
author_facet | Holeček, Milan |
author_sort | Holeček, Milan |
collection | PubMed |
description | Aspartate-glutamate carrier 2 (AGC2, citrin) is a mitochondrial carrier expressed in the liver that transports aspartate from mitochondria into the cytosol in exchange for glutamate. The AGC2 is the main component of the malate-aspartate shuttle (MAS) that ensures indirect transport of NADH produced in the cytosol during glycolysis, lactate oxidation to pyruvate, and ethanol oxidation to acetaldehyde into mitochondria. Through MAS, AGC2 is necessary to maintain intracellular redox balance, mitochondrial respiration, and ATP synthesis. Through elevated cytosolic Ca(2+) level, the AGC2 is stimulated by catecholamines and glucagon during starvation, exercise, and muscle wasting disorders. In these conditions, AGC2 increases aspartate input to the urea cycle, where aspartate is a source of one of two nitrogen atoms in the urea molecule (the other is ammonia), and a substrate for the synthesis of fumarate that is gradually converted to oxaloacetate, the starting substrate for gluconeogenesis. Furthermore, aspartate is a substrate for the synthesis of asparagine, nucleotides, and proteins. It is concluded that AGC2 plays a fundamental role in the compartmentalization of aspartate and glutamate metabolism and linkage of the reactions of MAS, glycolysis, gluconeogenesis, amino acid catabolism, urea cycle, protein synthesis, and cell proliferation. Targeting of AGC genes may represent a new therapeutic strategy to fight cancer. |
format | Online Article Text |
id | pubmed-10390287 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Korean Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-103902872023-08-01 Aspartate-glutamate carrier 2 (citrin): a role in glucose and amino acid metabolism in the liver Holeček, Milan BMB Rep Contributed Mini Review Aspartate-glutamate carrier 2 (AGC2, citrin) is a mitochondrial carrier expressed in the liver that transports aspartate from mitochondria into the cytosol in exchange for glutamate. The AGC2 is the main component of the malate-aspartate shuttle (MAS) that ensures indirect transport of NADH produced in the cytosol during glycolysis, lactate oxidation to pyruvate, and ethanol oxidation to acetaldehyde into mitochondria. Through MAS, AGC2 is necessary to maintain intracellular redox balance, mitochondrial respiration, and ATP synthesis. Through elevated cytosolic Ca(2+) level, the AGC2 is stimulated by catecholamines and glucagon during starvation, exercise, and muscle wasting disorders. In these conditions, AGC2 increases aspartate input to the urea cycle, where aspartate is a source of one of two nitrogen atoms in the urea molecule (the other is ammonia), and a substrate for the synthesis of fumarate that is gradually converted to oxaloacetate, the starting substrate for gluconeogenesis. Furthermore, aspartate is a substrate for the synthesis of asparagine, nucleotides, and proteins. It is concluded that AGC2 plays a fundamental role in the compartmentalization of aspartate and glutamate metabolism and linkage of the reactions of MAS, glycolysis, gluconeogenesis, amino acid catabolism, urea cycle, protein synthesis, and cell proliferation. Targeting of AGC genes may represent a new therapeutic strategy to fight cancer. Korean Society for Biochemistry and Molecular Biology 2023-07-31 2023-07-31 /pmc/articles/PMC10390287/ /pubmed/37254569 http://dx.doi.org/10.5483/BMBRep.2023-0052 Text en Copyright © 2023 by the The Korean Society for Biochemistry and Molecular Biology https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Contributed Mini Review Holeček, Milan Aspartate-glutamate carrier 2 (citrin): a role in glucose and amino acid metabolism in the liver |
title | Aspartate-glutamate carrier 2 (citrin): a role in glucose and amino acid metabolism in the liver |
title_full | Aspartate-glutamate carrier 2 (citrin): a role in glucose and amino acid metabolism in the liver |
title_fullStr | Aspartate-glutamate carrier 2 (citrin): a role in glucose and amino acid metabolism in the liver |
title_full_unstemmed | Aspartate-glutamate carrier 2 (citrin): a role in glucose and amino acid metabolism in the liver |
title_short | Aspartate-glutamate carrier 2 (citrin): a role in glucose and amino acid metabolism in the liver |
title_sort | aspartate-glutamate carrier 2 (citrin): a role in glucose and amino acid metabolism in the liver |
topic | Contributed Mini Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10390287/ https://www.ncbi.nlm.nih.gov/pubmed/37254569 http://dx.doi.org/10.5483/BMBRep.2023-0052 |
work_keys_str_mv | AT holecekmilan aspartateglutamatecarrier2citrinaroleinglucoseandaminoacidmetabolismintheliver |