Disease relevance of Ro 12-1989

• The proportion of dihomo-gamma-linolenic acid (20:3n-6) in serum phospholipids was inversely related to insulin sensitivity both before (r = -0.48, P < 0.001) and after (r = -0.46, P < 0.001) weight loss, but it did not change significantly in either group [1].
• Uptake and metabolism of exogenous eicosa-8,11,14-trienoic acid in minimal deviation hepatoma 7288 C cells [2].
• The most significant findings in eczema patient MNC were reduced ratios of 20:4n-6/20:3n-6 in total lipids and in phosphatidyl ethanolamine (PE) and of 20:4n-6/18:2n-6 in both total lipids, phosphatidyl choline (PC) and PE [3].
• PN applied to malnourished patients with cystic fibrosis results in beneficial effects in a subgroup characterized by the presence of DHLA in serum; for the group as a whole, the positive effects are minimal [4].
• Results showed that both spontaneous hypertension and salt-loading suppressed the desaturation of radiolabeled 18:2n-6 and of 20:3n-6 [5].

Psychiatry related information on Ro 12-1989

• Linoleic acid (18:2n-6), the precursor of the n-6 fatty acids, was below normal in intermittent explosive disorder, but the dihomogammalinolenic acid (DGLA) (20:3n-6) and some subsequent n-6 acids were at the same time elevated among all offenders [6].

High impact information on Ro 12-1989

• Prostaglandins are synthesized from eicosa-8,11,14-trienoic acid and eicosa-5,8,11-14-tetraenoic acid by smooth muscle cell cultures from guinea pig aorta [7].
• Addition of arachidonic acid and homo-gamma-linolenic acid to a suspension of rabbit peritoneal neutrophils led to the synthesis of 5-L-hydroxy-6,8,11,14-eicosatetraenoic acid and 8-L-hydroxy-9,11,14-eicosatrienoic acid, respectively [8].
• Supplementing the diet of C. elegans with dihommogamma-linolenic acid (20:3n-6, DGLA), a long chain omega-6 polyunsaturated fatty acid, results in sterile worms that lack germ cells [9].
• Ingestion of a diet rich in evening primrose oil elevates concentrations of dihomo-gamma-linolenic acid (DGLA; 20:3n-6), which results in the production of 1-series PGs, eg, PGE(1) [10].
• Low amounts of 20:3n-6 in umbilical arteries and veins and low amounts of 20:5n-3 in maternal platelets may contribute to the dominance of eicosanoids derived from 20:4n-6 [11].

Biological context of Ro 12-1989

• Beyond 30, 20, and 60 microM of 18:2n-6, 20:3n-6, and 18:3n-3 concentration, respectively, the enzyme activity deviated from Michaelis-Menten kinetics, suggesting an inhibition by excess substrate which is unlikely to occur in vivo as endogenous substrate concentration is much lower [12].
• These results demonstrate in term baboon neonates that in vivo 1) 20:4n-6 was retroconverted to 20:3n-6, 2) 20:4n-6 did not contribute significantly to de novo lipogenesis of saturates and monounsaturates, and 3) the preformed 20:4n-6 contribution to brain 22:4n-6 accumulation was quantitatively a significant metabolic fate for dietary 20:4n-6 [13].
• Preincubating the highly TNF-sensitive WEHI clone 13 cells for 44 hr with 50 mumol/L of 20:5n-3, 22:6n-3, 18:3n-6, 20:3n-6 or 20:4n-6 reduced cell survival 22 hr after challenge with TNF (40 ng/L) by 65%, 72%, 60%, 98% and 85%, respectively [14].
• During the course of lactation the levels of n-6 metabolites, e.g. 18:3n-6, 20:3n-6 and 20:4n-6, in milk fat declined progressively [15].
• Pulmonary function improved in patients who normalized their DHLA levels (vital capacity increased from 2.2 +/- 0.3 to 2.6 +/- 0.3 area %, p < 0.05), whereas those who continued to have undetectable levels of DHLA deteriorated (forced expiratory volume in 1 s decreased from 0.7 +/- to 0.6 +/- 0.1, p < 0.001) [4].

Anatomical context of Ro 12-1989

• Compared to splenic membranes from +Cu mice, the samples from -Cu mice demonstrated significant changes in all FAME (lower 16:0, 18:0 and 20:3n-6 and higher 18:1n-9, 18:2n-6 and 20:4n-6), including a higher unsaturation index [16].
• The effect of various steroids on the incorporation and desaturation of eicosa-8,11,14-trienoic acid in normal hepatocytes and HTC cells was investigated [17].
• Desaturation of 20:3n-6 to 20:4n-6 decreases in washed microsomes as they lose an adsorbed cytosolic fraction (CF), but the enzymatic activity can be recovered as a function of CF concentration in the incubation medium [18].
• Aggregation upon thrombin had a negative correlation with the 20:3n-6/20: 4n-6 ratio in plasma CE and a positive correlation with 18:2n-6 in adipose tissue [19].
• delta 5 Desaturation of eicosa-8,11,14-trienoic acid to arachidonic acid was studied in rat liver microsomes [18].

Associations of Ro 12-1989 with other chemical compounds

• Significant (P less than 0.05) elevation of dihomo-gamma-linolenic acid (DGLA, 20:3n-6), an elongation product of GLA, was revealed in PMN phospholipids after ingestion of either 0.48 or 1.5 g GLA-enriched oil/d. This elevation of DGLA in the PMN phospholipids paralleled the decreased capacity of calcium ionophore-activated PMN to generate LTB4 [20].
• Mouse peritoneal macrophages metabolize dihomogammalinolenic acid (20:3n-6) primarily to 15-hydroxy-8,11,13-eicosatrienoic acid (15-OH-20:3) [21].
• In conclusion, dietary BO, enriched in gamma-linolenic acid (18:3n-6), significantly increased the proportions of both 20:3n-6 and 20:4n-6 in salmon liver phospholipids and also significantly increased the desaturation of both 18:2n-6 and 18:3n-3 in salmon hepatocytes [22].
• Human leukocytes were incubated with 18:4n-3 (20 microM or 10 microM), 20:5n-3 (20 microM) or 20:3n-6 (20 microM) and subsequently stimulated with 1 microM ionophore A23187 and 20:4n-6 (20 microM or 10 microM) [23].
• The conversion of 20:4n-3 and 20:3n-6 to the longer-chain 22:6n-3 and 22:5n-6 was enhanced by RO feeding in Atlantic salmon hepatocytes [24].

Gene context of Ro 12-1989

• In BOR and MIX animals, 20:3n-6 levels were significantly increased (P less than 0.05) in all phospholipids relative to SAF and MFO [25].
• The proportions of the major long-chain polyunsaturated fatty acids (LCP), 20:3n-6, 20:4n-6, 22:5n-3 and 22:6n-3, were highest at 1 week and decreased thereafter in both types of milk [26].

Analytical, diagnostic and therapeutic context of Ro 12-1989

• Likewise, plasma levels of 20:3n-6, 20: 5n-3, and 22:6n-3 were lower in Usher's syndrome type I compared with the control group [27].
• In conclusion, intravenous injection of a DGLA emulsion increased DGLA concentrations in immune cells within 1 h and suppressed the DTH reaction [28].
• Fat-free diet produces a reduction in the conversion of eicosa-8,11,14-trienoic acid to arachidonic acid [29].
• The concentrations of the fatty acids 20:3n-6 and 20:4n-6 were significantly reduced after 3.5 months with a vegan diet (P < 0.0001 and P < 0.01 respectively), but the concentration increased to baseline values with a lactovegetarian diet [30].
• The substrate of the reaction [1-14C]eicosa-8,11,14-trienoic acid (20:3n-6), was separated from the product [1-14C]eicosa-5,8,11,14-tetraenoic acid (20:4n-6) by reverse phase high-pressure liquid chromatography (RP-HPLC) [31].

References