| First Author | Kim W | Year | 2019 |
| Journal | Cell Metab | Volume | 29 |
| Issue | 4 | Pages | 856-870.e7 |
| PubMed ID | 30686744 | Mgi Jnum | J:275328 |
| Mgi Id | MGI:6303518 | Doi | 10.1016/j.cmet.2018.12.023 |
| Citation | Kim W, et al. (2019) Polyunsaturated Fatty Acid Desaturation Is a Mechanism for Glycolytic NAD(+) Recycling. Cell Metab 29(4):856-870.e7 |
| abstractText | The reactions catalyzed by the delta-5 and delta-6 desaturases (D5D/D6D), key enzymes responsible for highly unsaturated fatty acid (HUFA) synthesis, regenerate NAD(+) from NADH. Here, we show that D5D/D6D provide a mechanism for glycolytic NAD(+) recycling that permits ongoing glycolysis and cell viability when the cytosolic NAD(+)/NADH ratio is reduced, analogous to lactate fermentation. Although lesser in magnitude than lactate production, this desaturase-mediated NAD(+) recycling is acutely adaptive when aerobic respiration is impaired in vivo. Notably, inhibition of either HUFA synthesis or lactate fermentation increases the other, underscoring their interdependence. Consistent with this, a type 2 diabetes risk haplotype in SLC16A11 that reduces pyruvate transport (thus limiting lactate production) increases D5D/D6D activity in vitro and in humans, demonstrating a chronic effect of desaturase-mediated NAD(+) recycling. These findings highlight key biologic roles for D5D/D6D activity independent of their HUFA end products and expand the current paradigm of glycolytic NAD(+) regeneration. |
