Transfer of glucose hydrogens via acetyl-CoA, malonyl-CoA, and NADPH to fatty acids during de novo lipogenesis
العنوان: | Transfer of glucose hydrogens via acetyl-CoA, malonyl-CoA, and NADPH to fatty acids during de novo lipogenesis |
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المؤلفون: | Maria Paula Macedo, Ludgero C. Tavares, Paulo J. Oliveira, Getachew Debas Belew, José A. Teixeira, Ivan Viegas, João Rito, João Gabriel Silva, John G. Jones |
المصدر: | Journal of Lipid Research, Vol 60, Iss 12, Pp 2050-2056 (2019) Journal of Lipid Research J Lipid Res |
بيانات النشر: | Elsevier, 2019. |
سنة النشر: | 2019 |
مصطلحات موضوعية: | 0301 basic medicine, Male, pentose phosphate pathway, QD415-436, 030204 cardiovascular system & hematology, Pentose phosphate pathway, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 13c enrichment, Mice, 0302 clinical medicine, Endocrinology, Acetyl Coenzyme A, acetyl-coenzyme A, reduced nicotinamide adenine dinucleotide phosphate, Animals, malonyl-coenzyme A, Research Articles, chemistry.chemical_classification, Lipogenesis, Acetyl-CoA, Fatty Acids, Fatty acid, Cell Biology, Malonyl Coenzyme A, Mice, Inbred C57BL, deuterium nuclear magnetic resonance, 030104 developmental biology, Malonyl-CoA, Glucose, chemistry, NADP, Hydrogen |
الوصف: | Deuterated water ((2)H(2)O) is widely used for measuring de novo lipogenesis (DNL). (2)H is incorporated into fatty acids via exchange between body water and the hydrogens of acetyl-CoA, malonyl-CoA, and NADPH. Previous studies concluded that these exchanges are incomplete; therefore, fatty acid (2)H enrichment requires correcting. In mice, we measured the (2)H enrichment of fatty acid positions 2 and 3 and methyl hydrogens from [U-(2)H(7)]glucose to determine (2)H transfer from glucose to fatty acid via malonyl-CoA, NADPH, and acetyl-CoA, respectively. Positional fatty acid (2)H enrichments were compared with (13)C enrichment of the same sites from an equivalent amount of [U-(13)C(6)]glucose provided alongside the [U-(2)H(7)]glucose tracer. Transfer of glucose (2)H to fatty acid position 2 and methyl sites was low ((2)H enrichment of 0.06 ± 0.01 and 0.14 ± 0.01 relative to (13)C) indicating extensive exchange at both malonyl- and acetyl-CoA, respectively. Transfer of glucose (2)H into fatty acid position 3 was more extensive (0.46 ± 0.04 relative to (13)C, P < 10(−5) vs. position 2), indicating a more limited exchange of those glucose hydrogens that were transferred via NADPH. However, mice provided with [U-(13)C(6)]glucose and (2)H(2)O had equivalent (2)H enrichments of fatty acid positions 2 and 3, suggesting that in this setting, NADPH and body water (2)H had exchanged extensively. This is explained by contributions of substrates other than exogenous glucose to DNL coupled with their extensive (2)H enrichment from (2)H(2)O prior to DNL. Under such conditions, (2)H enrichment of fatty acids from (2)H(2)O does not need correction. |
اللغة: | English |
تدمد: | 0022-2275 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a9eb08f2bb46e8fed5ecc35fcaecfa73Test http://www.sciencedirect.com/science/article/pii/S0022227520310439Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....a9eb08f2bb46e8fed5ecc35fcaecfa73 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 00222275 |
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