One Carbon Metabolism and <i>S</i>-Adenosylmethionine in Non-Alcoholic Fatty Liver Disease Pathogenesis and Subtypes
One carbon metabolism (1CM) can be defined as the transfer of a carbon unit from one metabolite to another and its replenishment by different sources of labile methyl-group nutrients: primarily choline, methionine, betaine, and serine. This flow of carbon units allows the biosynthesis of nucleotides...
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| Format: | Article |
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MDPI AG
2022-10-01
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| Series: | Livers |
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| Online Access: | https://www.mdpi.com/2673-4389/2/4/20 |
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| author | David Fernández-Ramos Fernando Lopitz-Otsoa Oscar Millet Cristina Alonso Shelly C. Lu José M. Mato |
| author_facet | David Fernández-Ramos Fernando Lopitz-Otsoa Oscar Millet Cristina Alonso Shelly C. Lu José M. Mato |
| author_sort | David Fernández-Ramos |
| collection | DOAJ |
| description | One carbon metabolism (1CM) can be defined as the transfer of a carbon unit from one metabolite to another and its replenishment by different sources of labile methyl-group nutrients: primarily choline, methionine, betaine, and serine. This flow of carbon units allows the biosynthesis of nucleotides, amino acids, formylated methionyl-tRNA, polyamines, glutathione, phospholipids, detoxification reactions, maintenance of the redox status and the concentration of NAD, and methylation reactions including epigenetic modifications. That is, 1CM functions as a nutrient sensor and integrator of cellular metabolism. A critical process in 1CM is the synthesis of <i>S</i>-adenosylmethionine (SAMe), the source of essentially all the hundreds of millions of daily methyl transfer reactions in a cell. This versatility of SAMe imposes a tight control in its synthesis and catabolism. Much of our knowledge concerning 1CM has been gained from studies in the production and prevention of nonalcoholic fatty liver disease (NAFLD). Here, we discuss in detail the function of the most important enzymes for their quantitative contribution to maintaining the flux of carbon units through 1CM in the liver and discuss how alterations in their enzymatic activity contribute to the development of NAFLD. Next, we discuss NAFLD subtypes based on serum lipidomic profiles with different risk of cardiovascular disease. Among the latter, we highlight the so-called subtype A for its serum lipidomic profile phenocopying that of mice deficient in SAMe synthesis and because its high frequency (about 50% of the NAFLD patients). |
| first_indexed | 2024-03-09T16:11:16Z |
| format | Article |
| id | doaj.art-af6b287548474420bda934f8ae1f32e7 |
| institution | Directory Open Access Journal |
| issn | 2673-4389 |
| language | English |
| last_indexed | 2024-03-09T16:11:16Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Livers |
| spelling | doaj.art-af6b287548474420bda934f8ae1f32e72023-11-24T16:14:23ZengMDPI AGLivers2673-43892022-10-012424325710.3390/livers2040020One Carbon Metabolism and <i>S</i>-Adenosylmethionine in Non-Alcoholic Fatty Liver Disease Pathogenesis and SubtypesDavid Fernández-Ramos0Fernando Lopitz-Otsoa1Oscar Millet2Cristina Alonso3Shelly C. Lu4José M. Mato5Precision Medicine and Metabolism Laboratory, CIC bioGUNE, BRTA, CIBERehd, Technology Park of Bizkaia, 48160 Derio, Bizkaia, SpainPrecision Medicine and Metabolism Laboratory, CIC bioGUNE, BRTA, CIBERehd, Technology Park of Bizkaia, 48160 Derio, Bizkaia, SpainPrecision Medicine and Metabolism Laboratory, CIC bioGUNE, BRTA, CIBERehd, Technology Park of Bizkaia, 48160 Derio, Bizkaia, SpainOWL Metabolomics, Technology Park of Bizkaia, 48160 Derio, Bizkaia, SpainKarsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAPrecision Medicine and Metabolism Laboratory, CIC bioGUNE, BRTA, CIBERehd, Technology Park of Bizkaia, 48160 Derio, Bizkaia, SpainOne carbon metabolism (1CM) can be defined as the transfer of a carbon unit from one metabolite to another and its replenishment by different sources of labile methyl-group nutrients: primarily choline, methionine, betaine, and serine. This flow of carbon units allows the biosynthesis of nucleotides, amino acids, formylated methionyl-tRNA, polyamines, glutathione, phospholipids, detoxification reactions, maintenance of the redox status and the concentration of NAD, and methylation reactions including epigenetic modifications. That is, 1CM functions as a nutrient sensor and integrator of cellular metabolism. A critical process in 1CM is the synthesis of <i>S</i>-adenosylmethionine (SAMe), the source of essentially all the hundreds of millions of daily methyl transfer reactions in a cell. This versatility of SAMe imposes a tight control in its synthesis and catabolism. Much of our knowledge concerning 1CM has been gained from studies in the production and prevention of nonalcoholic fatty liver disease (NAFLD). Here, we discuss in detail the function of the most important enzymes for their quantitative contribution to maintaining the flux of carbon units through 1CM in the liver and discuss how alterations in their enzymatic activity contribute to the development of NAFLD. Next, we discuss NAFLD subtypes based on serum lipidomic profiles with different risk of cardiovascular disease. Among the latter, we highlight the so-called subtype A for its serum lipidomic profile phenocopying that of mice deficient in SAMe synthesis and because its high frequency (about 50% of the NAFLD patients).https://www.mdpi.com/2673-4389/2/4/20lipidomicsnon-alcoholic fatty liver disease subtypes<i>S</i>-adenosylmethionine |
| spellingShingle | David Fernández-Ramos Fernando Lopitz-Otsoa Oscar Millet Cristina Alonso Shelly C. Lu José M. Mato One Carbon Metabolism and <i>S</i>-Adenosylmethionine in Non-Alcoholic Fatty Liver Disease Pathogenesis and Subtypes Livers lipidomics non-alcoholic fatty liver disease subtypes <i>S</i>-adenosylmethionine |
| title | One Carbon Metabolism and <i>S</i>-Adenosylmethionine in Non-Alcoholic Fatty Liver Disease Pathogenesis and Subtypes |
| title_full | One Carbon Metabolism and <i>S</i>-Adenosylmethionine in Non-Alcoholic Fatty Liver Disease Pathogenesis and Subtypes |
| title_fullStr | One Carbon Metabolism and <i>S</i>-Adenosylmethionine in Non-Alcoholic Fatty Liver Disease Pathogenesis and Subtypes |
| title_full_unstemmed | One Carbon Metabolism and <i>S</i>-Adenosylmethionine in Non-Alcoholic Fatty Liver Disease Pathogenesis and Subtypes |
| title_short | One Carbon Metabolism and <i>S</i>-Adenosylmethionine in Non-Alcoholic Fatty Liver Disease Pathogenesis and Subtypes |
| title_sort | one carbon metabolism and i s i adenosylmethionine in non alcoholic fatty liver disease pathogenesis and subtypes |
| topic | lipidomics non-alcoholic fatty liver disease subtypes <i>S</i>-adenosylmethionine |
| url | https://www.mdpi.com/2673-4389/2/4/20 |
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