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Transfer of glucose hydrogens via acetyl-CoA, malonyl-CoA, and NADPH to fatty acids during de novo lipogenesis.
Journal of Lipid Research ( IF 5.0 ) Pub Date : 2019-10-01 , DOI: 10.1194/jlr.ra119000354
Getachew Debas Belew 1 , Joao Silva 1 , Joao Rito 1 , Ludgero Tavares 1 , Ivan Viegas 1, 2 , Jose Teixeira 1 , Paulo J Oliveira 1 , Maria Paula Macedo 3, 4, 5 , John G Jones 4, 6
Affiliation  

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.

中文翻译:

在从头脂肪形成过程中,通过乙酰基-CoA,丙二酰-CoA和NADPH将葡萄糖氢转移至脂肪酸。

氘化水(2 H 2 O)被广泛用于测量新生脂肪形成(DNL)。通过人体水与乙酰辅酶A,丙二酰辅酶A和NADPH的氢之间的交换将2 H引入脂肪酸中。先前的研究得出结论,这些交流是不完整的。因此,脂肪酸2 H的富集需要校正。在小鼠中,我们测量了脂肪酸2和3的2 H富集以及[U- 2 H 7 ]葡萄糖中的甲基氢,以确定通过丙二酰CoA,NADPH和乙酰基CoA从葡萄糖向脂肪酸的2 H转移,分别。比较了位置脂肪酸2 H富集与从[U- 2 H 7 ]葡萄糖示踪剂旁边提供的等量[U- 13 C 6 ]葡萄糖中13 C富集相同的位点。葡萄糖2 H向脂肪酸2位和甲基位的转移很低(相对于13 C,2 H富集度为0.06±0.01和0.14±0.01 ),表明分别在丙二酰-CoA和乙酰-CoA上进行了广泛交换。葡萄糖2 H向脂肪酸3位的转移更广泛(相对于13 C为0.46±0.04 ,P <10 -5相对于位置2),表明通过NADPH转移的那些葡萄糖氢的交换更为有限。但是,提供有[U- 13 C 6 ]葡萄糖和2 H 2 O的小鼠的脂肪酸2和3位具有2 H富集,表明在这种情况下,NADPH和人体水分2 H交换广泛。这是通过其他基板的贡献比外源性葡萄糖到DNL加上其广泛的解释2选自H富集2 ħ 2 O之前DNL。在这种条件下,从2 H 2中富集2 H脂肪酸O不需要校正。
更新日期:2020-08-21
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