出版社：American Society for Biochemistry and Molecular Biology
摘要：Many patients with X-linked retinitis pigmentosa (XLRP) have lower than normal blood levels of the long-chain polyunsaturated ω3 fatty acid docosahexaenoic acid (DHA; 22:6 ω3). This clinical trial was designed to test whether down-regulation of DHA biosynthesis might be responsible for these reduced DHA levels. DHA biosynthesis was assessed in five severely affected patients with XLRP and in five age-matched controls by quantifying conversion of [U-13C] α-linolenic acid (α-LNA) to [13C]DHA. Following oral administration of [U-13C]α-LNA, blood samples were collected at designated intervals for 21 days and isotopic enrichment of all Ω3 fatty acids was determined by gas chromatography/mass spectroscopy. Activity of each metabolic step in the conversion of α-LNA to DHA was determined by comparison of the ratios of the integrated concentration of 13C-product to 13C-precursor in plasma total lipid fractions. The ratio of [13C]DHA to [13C]18:3 Ω3 (the entire pathway) and that of [13C]20:5 Ω3 to [13C]20:4 Ω3 (Δ5-desaturase) were significantly lower in patients versus controls ( P = 0.03 and 0.05, respectively). The estimated biosynthetic rates of [13C]20:5 Ω3, [13C]22:5 Ω3, [13C]24:5 Ω3, [13C]24:6 Ω3, and [13C]22:6 Ω3 were significantly lower in XLRP patients (42%, 43%, 31%, 18%, and 32% of control values, respectively; P 5-desaturase in XLRP. The disappearance of 13C-labeled fatty acids from plasma was not greater in XLRP patients compared with controls, suggesting that XLRP was not associated with increased rates of fatty acid oxidation or other routes of catabolism. Thus, despite individual variation among both patients and controls, the data are consistent with a lower rate of Δ5-desaturation, suggesting that decreased biosynthesis of DHA may contribute to lower blood levels of DHA in patients with XLRP. —Hoffman, D. R., J. C. DeMar, W. C. Heird, D. G. Birch, and R. E. Anderson. Impaired synthesis of DHA in patients with X-linked retinitis pigmentosa. J. Lipid Res. 2001. 42: 1395–1401.
