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：

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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。