Transfer of glucose hydrogens via acetyl-CoA, malonyl-CoA, and NADPH to fatty acids during de novo lipogenesis.
J Lipid Res
; 60(12): 2050-2056, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31575642
ABSTRACT
Deuterated water (2H2O) is widely used for measuring de novo lipogenesis (DNL). 2H 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 2H enrichment requires correcting. In mice, we measured the 2H enrichment of fatty acid positions 2 and 3 and methyl hydrogens from [U-2H7]glucose to determine 2H transfer from glucose to fatty acid via malonyl-CoA, NADPH, and acetyl-CoA, respectively. Positional fatty acid 2H enrichments were compared with 13C enrichment of the same sites from an equivalent amount of [U-13C6]glucose provided alongside the [U-2H7]glucose tracer. Transfer of glucose 2H to fatty acid position 2 and methyl sites was low (2H enrichment of 0.06 ± 0.01 and 0.14 ± 0.01 relative to 13C) indicating extensive exchange at both malonyl- and acetyl-CoA, respectively. Transfer of glucose 2H into fatty acid position 3 was more extensive (0.46 ± 0.04 relative to 13C, 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-13C6]glucose and 2H2O had equivalent 2H enrichments of fatty acid positions 2 and 3, suggesting that in this setting, NADPH and body water 2H had exchanged extensively. This is explained by contributions of substrates other than exogenous glucose to DNL coupled with their extensive 2H enrichment from 2H2O prior to DNL. Under such conditions, 2H enrichment of fatty acids from 2H2O does not need correction.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Acetilcoenzima A
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Lipogênese
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Ácidos Graxos
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Glucose
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Hidrogênio
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Malonil Coenzima A
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NADP
Limite:
Animals
Idioma:
En
Revista:
J Lipid Res
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Portugal
País de publicação:
EEUU
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ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA