The retina and retinal pigment epithelium differ in nitrogen metabolism and are metabolically connected
| Autor: | Kaizheng Gong, Xinnong Liu, Brianna Ritz, Jiancheng Huang, Jianhai Du, Chen Zhao, Yekai Wang, Rong Xu |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Retinal degeneration Nitrogen Retinal Pigment Epithelium Models Biological Biochemistry 03 medical and health sciences chemistry.chemical_compound Ammonium Compounds medicine Animals Amino Acids Pyruvates Molecular Biology Alanine chemistry.chemical_classification Retina Retinal pigment epithelium Nitrogen Isotopes 030102 biochemistry & molecular biology Choroid Retinal Cell Biology Metabolism medicine.disease eye diseases Mitochondria Amino acid Cell biology Mice Inbred C57BL Glutamine 030104 developmental biology medicine.anatomical_structure chemistry Organ Specificity Retinaldehyde sense organs |
| Zdroj: | J Biol Chem |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.ra119.011727 |
| Popis: | Defects in energy metabolism in either the retina or the immediately adjacent retinal pigment epithelium (RPE) underlie retinal degeneration, but the metabolic dependence between retina and RPE remains unclear. Nitrogen-containing metabolites such as amino acids are essential for energy metabolism. Here, we found that (15)N-labeled ammonium is predominantly assimilated into glutamine in both the retina and RPE/choroid ex vivo. [(15)N]Ammonium tracing in vivo show that, like the brain, the retina can synthesize asparagine from ammonium, but RPE/choroid and the liver cannot. However, unless present at toxic concentrations, ammonium cannot be recycled into glutamate in the retina and RPE/choroid. Tracing with (15)N-labeled amino acids show that the retina predominantly uses aspartate transaminase for de novo synthesis of glutamate, glutamine, and aspartate, whereas RPE uses multiple transaminases to utilize and synthesize amino acids. Retina consumes more leucine than RPE, but little leucine is catabolized. The synthesis of serine and glycine is active in RPE but limited in the retina. RPE, but not the retina, uses alanine as mitochondrial substrates through mitochondrial pyruvate carrier. However, when the mitochondrial pyruvate carrier is inhibited, alanine may directly enter the retinal mitochondria but not those of RPE. In conclusion, our results demonstrate that the retina and RPE differ in nitrogen metabolism and highlight that the RPE supports retinal metabolism through active amino acid metabolism. |
| Databáze: | OpenAIRE |
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