ライフサイエンスコーパス: VLCFA

1 VLCFA binding was monitored in real time with the fluore

2 VLCFA levels are increased at day of birth, thus providi

3 VLCFA levels were increased in all patients homozygous f

4 VLCFAs are components of a variety of compounds, for exa

5 VLCFAs promote septin recruitment to curved plasma membr

6 VLCFAs subsequently accumulate in tissues, including the

7 of ALD, compound 27 treatment reduced C26:0 VLCFA concentrations to near-wild-type levels in blood a

8 elective inhibitor of ELOVL1, reducing C26:0 VLCFA synthesis in ALD patient fibroblasts and lymphocyt

9 selectively inhibits ELOVL1, reducing C26:0 VLCFA synthesis in ALD patient fibroblasts, lymphocytes,

10 These data lead us to conclude that (1) VLCFA levels are independent of peroxisomal fatty acid b

11 ulating levels of several species of omega-3 VLCFAs (C24-C28) with previously uncharacterized physiol

12 nctional protein deficiency--also accumulate VLCFA, but they present during the neonatal period.

13 VLCFA beta-oxidation but does not accumulate VLCFA.

14 X-ALD mice, which accumulate VLCFA in tissues, show no change in the expression of Vl

15 ng enzyme of the very-long-chain fatty acid (VLCFA) beta-oxidation pathway in peroxisomes and leads t

16 uced peroxisomal very long chain fatty acid (VLCFA) beta-oxidation.

17 he regulation of very long chain fatty acid (VLCFA) biosynthesis in Brassica napus embryos.

18 f, except in the very long-chain fatty acid (VLCFA) class wherein acids longer than 24 carbons (C(24)

19 nd the resultant very long chain fatty acid (VLCFA) derangement has dramatically opposing effects in

20 ) contained only very-long-chain fatty acid (VLCFA) derivatives such as alcohols, alkyl esters, aldeh

21 ably, an unusual very-long-chain fatty acid (VLCFA) is found in the lipid A of R. leguminosarum as we

22 ical, and plasma very-long-chain fatty acid (VLCFA) measurements were used to evaluate the effect of

23 ein required for very long chain fatty acid (VLCFA) metabolism.

24 the synthesis of very-long-chain fatty acid (VLCFA) precursors of cuticular waxes.

25 rase activity on very-long-chain fatty acid (VLCFA) substrates and exhibit diverse regiospecificity,

26 ted the roles of very long-chain fatty acid (VLCFA) synthesis by fatty acid elongase 3 (ELO3) in the

27 (eIF2B) and the very-long-chain fatty acid (VLCFA) synthesis keto-reductase enzyme YBR159W physicall

28 human hub of the very-long-chain fatty acid (VLCFA) synthesis pathway and core interactor.

29 mes required for very long-chain fatty acid (VLCFA) synthesis.

30 cessive steps in very-long-chain fatty acid (VLCFA) synthesis.

31 the peroxisomal very long-chain fatty acid (VLCFA) transporter.

32 modified with a very-long-chain fatty acid (VLCFA; C > or = 28) and we discovered that BacA is invol

33 ions accumulate very-long-chain fatty acids (VLCFA) (carbon length >22).

34 Very-long-chain fatty acids (VLCFA) and branched-chain fatty acids (BCFA) are potent

35 ed de novo from very long-chain fatty acids (VLCFA) and sphingoid long-chain bases, which are amide l

36 ich catabolizes very long chain fatty acids (VLCFA), increases in the context of obesity, but how thi

37 e of activating very long-chain fatty acids (VLCFA), one is a bile acid-CoA synthetase, and others ha

38 accumulation of very long-chain fatty acids (VLCFA).

39 rt of saturated very long chain fatty acids (VLCFA; >C18:0) contribute to their toxic levels in perox

40 vated levels of very-long-chain fatty acids (VLCFA; C(>22:0)) that have been attributed to reduced pe

41 ls of saturated very long-chain fatty acids (VLCFA; carbon chains of 22 or more) in tissues and plasm

42 ort, leading to very long-chain fatty acids (VLCFAs) accumulation.

43 for example, of very long-chain fatty acids (VLCFAs) and plasmalogens, the ER also plays a role in pe

44 ta-oxidation of very long chain fatty acids (VLCFAs) and reduced function of peroxisomal very long ch

45 Long-chain and very-long-chain fatty acids (VLCFAs) are also metabolized by the cytochrome P450 CYP4

46 Very long-chain fatty acids (VLCFAs) are essential lipids whose functional diversity

47 Very long chain fatty acids (VLCFAs) are precursors to sphingolipids, glycerophosphol

48 id species, the very-long-chain fatty acids (VLCFAs) are relatively rare and poorly understood.

49 Accumulation of very long chain fatty acids (VLCFAs) due to defects in ATP binding cassette protein D

50 accumulation of very long chain fatty acids (VLCFAs) due to impaired peroxisomal beta-oxidation.

51 he extension of very-long-chain fatty acids (VLCFAs) for the synthesis of specialized apoplastic lipi

52 the contents of very long-chain fatty acids (VLCFAs) in akr2a mutants were decreased, and the express

53 biosynthesis of very-long-chain fatty acids (VLCFAs) in yeast.

54 nsport acylated very long chain fatty acids (VLCFAs) into the peroxisome for degradation.

55 pids containing very long-chain fatty acids (VLCFAs) promote homotypic vacuolar fusion in Saccharomyc

56 f corresponding very long-chain fatty acids (VLCFAs) species (C22-28) compared to the skin without S.

57 on of LCFAs and very-long-chain fatty acids (VLCFAs) that mediate lipotoxicity.

58 transporter of very-long-chain fatty acids (VLCFAs), ABCD1.

59 vated levels of very long chain fatty acids (VLCFAs), as seen in the human disease adrenoleukodystrop

60 assay of plasma very long chain fatty acids (VLCFAs), developed in our laboratory in 1981, has become

61 ryzae, requires very-long-chain fatty acids (VLCFAs), which act as mediators of septin organization a

62 gase to produce very long chain fatty acids (VLCFAs), which are building blocks of diverse lipids.

63 biosynthesis of very long chain fatty acids (VLCFAs).

64 tion to produce very-long-chain fatty acids (VLCFAs).

65 or formation of very long chain fatty acids (VLCFAs, or fatty acids with chain lengths > 18 carbons).

66 al educts (like very-long-chain fatty acids [VLCFAs] or branched-chain fatty acids) and lack of produ

67 n that contain enzymes capable of activating VLCFA.

68 istantly related very-long-chain fatty acyl (VLCFA) desaturases from Arabidopsis, ADS1.2 and ADS1.4,

69 Reverse genetic experiments found additional VLCFA and lipid metabolism-related mutants with increase

70 elo2 or scelo3 single mutants did not affect VLCFA profiles.

71 rance via an interaction with KCS1 to affect VLCFA biosynthesis in Arabidopsis.

72 Likewise, the high affinity VLCFA-CoA and BCFA-CoA altered cofactor recruitment to P

73 own by circular dichroism, the high affinity VLCFA-CoA and BCFA-CoA strongly altered PPARalpha confor

74 Although necessary for the elongation of all VLCFAs, known condensing enzymes cannot efficiently synt

75 bits decreased peroxisomal VLCS activity and VLCFA beta-oxidation but does not accumulate VLCFA.

76 rect effect on peroxisomal VLCS activity and VLCFA beta-oxidation by transporting fatty acid substrat

77 ndings highlight peroxisomal dysfunction and VLCFA metabolism as pivotal regulators of ISC aging and

78 a key factor in the coordination of Pro and VLCFA metabolism.

79 In particular, Pro and VLCFA synthesis share dual roles to help buffer cellular

80 hway controls Elo2 phosphorylation state and VLCFA synthesis.

81 t that ACBD5 may act as a primary tether and VLCFA recruitment factor, whereas ACBD4 may have regulat

82 g and very long-chain fatty acids (LCFAs and VLCFAs) and depletion of phosphatidylinositol and phosph

83 ine species containing unsaturated LCFAs and VLCFAs.

84 Because VLCFA diffuse through the lipid bilayer, proteins may no

85 platform to explore the relationship between VLCFA profiles and cellular physiology.

86 synthetase that preferentially modifies both VLCFAs for wax synthesis and long-chain (C(16)) fatty ac

87 organ, hsBG may play a central role in brain VLCFA metabolism and myelinogenesis.

88 r the CoA thioesters of the common (C20-C24) VLCFA.

89 sm that generates the repertoire of cellular VLCFAs.

90 , and Garcinia spicata) had waxes containing VLCFA derivatives, together with high percentages of ali

91 expression in vascular tissue may contribute VLCFA for barrier lipid synthesis and reflects the ances

92 tify a regulatory mechanism for coordinating VLCFA synthesis with sphingolipid metabolism and link si

93 pharmacological agents resulted in decreased VLCFA levels without a change in VLCFA beta-oxidation ac

94 ccumulation has been attributed to decreased VLCFA beta-oxidation and peroxisomal very long-chain acy

95 ce of a possible link between Elo3-dependent VLCFA synthesis, and IP metabolism by KCS1 and IPK2 in t

96 ctively, blocked their ability to desaturate VLCFAs.

97 cultured cells and the absorption of dietary VLCFAs in mice.

98 atment of diseases characterized by elevated VLCFA levels.

99 nogaster mutant bubblegum (BGM) had elevated VLCFA and that the product of the defective gene had seq

100 h ALD, zebrafish abcd1 mutants have elevated VLCFA levels.

101 laboratory and others have reported elevated VLCFA levels and reduced peroxisomal VLCFA beta-oxidatio

102 ation in tissues from ALD mice with elevated VLCFA levels.

103 involved in wax synthesis can only elongate VLCFAs up to 28 carbons (C28) in length, despite the pre

104 n of KCS1 in the akr2a mutants could enhance VLCFAs contents and chilling tolerance.

105 eate oil, blocked the accumulation of excess VLCFAs as well as development of the pathology.

106 urther showed that cyclodextrins can extract VLCFA rapidly (within seconds) from vesicles and cells,

107 both for the uptake of very long chain FAs (VLCFAs) in cultured cells and the absorption of dietary

108 me A synthetase Fat1, which is essential for VLCFA utilization, results in ER stress with compensator

109 ustrating that the predominant mechanism for VLCFA absorption is CD36-dependent.

110 rated that LACS1 has synthetase activity for VLCFAs C(20)-C(30), with highest activity for C(30) acid

111 is and suggest an unexpected requirement for VLCFAs in Ole1 function.

112 VLCFAs of Arabidopsis result primarily from VLCFA desaturation, rather than by elongation of long ch

113 The full VLCFA biosynthetic machinery and how this machinery gene

114 mice receiving LXR agonist in their diet had VLCFA reductions in ALD-relevant tissues.

115 f obligate heterozygotes had abnormally high VLCFA levels, but a normal result does not exclude carri

116 oxisomes of X-ALD mouse fibroblasts improves VLCFA beta-oxidation in these cells, implying a role for

117 Although this suggests a role of ABCD1 in VLCFA import into peroxisomes, no direct experimental ev

118 1-knockdown and the subsequent alteration in VLCFA metabolism in human U87 astrocytes and rat B12 oli

119 depletion of HSD17B12 induces alterations in VLCFA-containing lipid species and a drastic reduction o

120 n decreased VLCFA levels without a change in VLCFA beta-oxidation activity.

121 n studies to begin analysis of their role in VLCFA beta-oxidation and on the peroxisomal membrane.

122 used as an industrial feedstock, is rich in VLCFAs, whereas the edible oil extracted from canola is

123 ith a high erucic acid content had increased VLCFA levels, but the application of a discriminant func

124 hen ALDP is deficient in X-ALD, in increased VLCFA accumulation despite normal peroxisomal VLCFA beta

125 Despite this increased VLCFA activation, hsBG-expressing cells did not have inc

126 Moreover, intestinal VLCFA absorption is completely abolished in CD36-null mi

127 bon addition that elongated shorter FAs into VLCFAs whose length was dictated by the specific Elop ho

128 shift from saturated toward monounsaturated VLCFA and normalizing phospholipid profiles.

129 in ALD fibroblasts, whereas monounsaturated VLCFA did not.

130 the 24-carbon and 26-carbon monounsaturated VLCFAs of Arabidopsis result primarily from VLCFA desatu

131 ic rerouting of saturated to monounsaturated VLCFAs may alleviate lipid toxicity, a strategy that may

132 ion is an effective approach for normalizing VLCFAs in models of ALD.

133 These rescued strains express novel VLCFA profiles reflecting the different catalytic capabi

134 ein directly involved in the biosynthesis of VLCFA-modified lipid A.

135 lization of Vlcs protein, and the control of VLCFA levels does not depend on the direct interaction o

136 In these patients the degree of VLCFA excess correlated with clinical severity.

137 membrane remodeling or an adverse effect of VLCFA dysfunction.

138 Here we show that Elo2, a key enzyme of VLCFA synthesis, is controlled by signaling of the guani

139 idation activity and increased expression of VLCFA synthesizing enzymes, elongase of very long chain

140 Loss of VLCFA synthesis via deletion of ELO3 reduced telomere le

141 ate that ALDP does not determine the rate of VLCFA beta-oxidation and that VLCFA levels are not deter

142 CFA levels are not determined by the rate of VLCFA beta-oxidation.

143 essing cells did not have increased rates of VLCFA degradation.

144 Little is known concerning the regulation of VLCFA levels and how cells coordinate their synthesis wi

145 epleted cells, supporting a specific role of VLCFA in HCV life cycle.

146 es to the endoplasmic reticulum, the site of VLCFA biosynthesis.

147 and the extremely low aqueous solubility of VLCFA precludes addition of unbound VLCFA to lipid membr

148 lysophosphatidyl choline (LPC), a subtype of VLCFA, in the blood of ATP binding cassette transporter

149 onally, we discovered that in the absence of VLCFAs, S. meliloti produces novel pentaacylated lipid A

150 n peroxisome-ER contacts and accumulation of VLCFAs.

151 connections or result in the accumulation of VLCFAs.

152 chondrial abnormalities, and accumulation of VLCFAs.

153 uding chilling sensitivity and a decrease of VLCFAs contents.

154 to curved plasma membranes and depletion of VLCFAs prevents septin assembly and host penetration by

155 tracted from canola is essentially devoid of VLCFAs.

156 atalyze the substrate-specific elongation of VLCFAs.

157 An excess of VLCFAs disrupts essential homeostatic functions crucial

158 In patient fibroblasts, an excess of VLCFAs triggers mitochondrial fragmentation through the

159 s accumulate substantially reduced levels of VLCFAs.

160 ed oil composition to contain high levels of VLCFAs.

161 Its role in the beta-oxidation of VLCFAs and its effect on the function of VLCS are unclea

162 ALD mouse exhibits reduced beta-oxidation of VLCFAs, resulting in significantly elevated levels of sa

163 PEX5-mediated peroxisomal beta-oxidation of VLCFAs.

164 an increase in the rate of beta-oxidation of VLCFAs.

165 for efficient peroxisomal beta-oxidation of VLCFAs.

166 to contact site formation and recruitment of VLCFAs to peroxisomes remain unclear.

167 t showed divergent product profiles based on VLCFA length, saturation, and position of the double bon

168 h either long-chain fatty acid (2.4-fold) or VLCFA (2.6-fold) substrates.

169 her members of the translation initiation or VLCFA pathways.

170 , we hypothesize that sphingolipids or other VLCFA-containing compounds are essential for normal embr

171 se (VLCS) activity and decreased peroxisomal VLCFA beta-oxidation.

172 LCFA accumulation despite normal peroxisomal VLCFA beta-oxidation in ALD mouse tissues.

173 The rate of peroxisomal VLCFA beta-oxidation in human and mouse fibroblasts in v

174 study, we found normal levels of peroxisomal VLCFA beta-oxidation in tissues from ALD mice with eleva

175 To unravel the mechanism of peroxisomal VLCFA transport, we use Saccharomyces cerevisiae as a mo

176 have been attributed to reduced peroxisomal VLCFA beta-oxidation activity.

177 levated VLCFA levels and reduced peroxisomal VLCFA beta-oxidation in human and mouse X-ALD fibroblast

178 high levels of fatty acid elongation and PL-VLCFA accumulation that occur in HCMV-infected cells.

179 The levels of many PL-VLCFAs were lower in subUL37x1-infected cells than in WT

180 ds with very-long-chain fatty acid tails (PL-VLCFAs) that contain 26 or more carbons in one of their

181 ids, particularly those with VLCFA tails (PL-VLCFAs).

182 Plasma VLCFA concentrations decreased by 55% and remained sligh

183 These phenotypes include reduced VLCFA synthesis, accumulation of high levels of dihydros

184 Expression of either ALDP or PMP70 restores VLCFA beta-oxidation in X-ALD fibroblasts, indicating ov

185 Importantly, saturated VLCFAs caused ER stress in ALD fibroblasts, whereas mono

186 1 expression led to an increase in saturated VLCFAs, and CRISPR knockout of scd1 in zebrafish mimicke

187 n significantly elevated levels of saturated VLCFAs in total lipids from all tissues measured and in

188 iciency results in accumulation of saturated VLCFAs.

189 increased SCD1 levels and reduced saturated VLCFAs.

190 novel synthases with correspondingly shorter VLCFA outputs.

191 using methyl-beta-cyclodextrin to solubilize VLCFA for rapid delivery to "acceptor" phosphatidylcholi

192 very slowly growing) and do synthesize some VLCFA.

193 ork for tailoring the production of specific VLCFAs.

194 ensing enzymes cannot efficiently synthesize VLCFAs longer than 28 carbons, despite the prevalence of

195 y long-chain fatty acid acyl-CoA synthetase (VLCFA-ACS) activity, as negative regulators of RPE65.

196 ne the rate of VLCFA beta-oxidation and that VLCFA levels are not determined by the rate of VLCFA bet

197 We observed that VLCFA biosynthesis inhibitors not only prevent rice blas

198 We previously showed that VLCFA desorb much slower than normal dietary fatty acids

199 rtmentalizes Tsc13p at NV junctions and that VLCFAs contribute to the normal biogenesis of trilaminar

200 These results indicate that VLCFAs play essential roles in protein quality control a

201 Kd = 20 nM), PPARalpha only weakly bound the VLCFA.

202 mide(42:2)-3, lipid species that contain the VLCFA 24:1(n-9), and trihydroxy-glycosylinositolphosphoc

203 anilide hydroxamic acid (SAHA) corrected the VLCFA derangement both in vitro and in vivo, and inhibit

204 and other strains with null mutations in the VLCFA pathway cause eIF2B to appear as numerous foci thr

205 revealed that the mutant lipid A lacked the VLCFA.

206 henotypes of an acpXL mutant which lacks the VLCFA.

207 essary for the synthesis and transfer of the VLCFA to the lipid A.

208 Here, we show that loss of the VLCFA-coenzyme A synthetase Fat1, which is essential for

209 We found that the VLCFA derivative lignoceroyl (C24:0)-CoA inhibited synth

210 zed acyl carrier protein AcpXL, on which the VLCFA is built.

211 rane for subsequent re-esterification of the VLCFAs.

212 Three VLCFA parameters, the level of hexacosanoic acid (C26:0)

213 e elongase Elo3 adds the last two carbons to VLCFAs that are incorporated into sphingolipids.

214 ility of VLCFA precludes addition of unbound VLCFA to lipid membranes.

215 Whereas VLCFA synthesis is essential for viability, the ybr159De

216 Elop active site faces the cytosol, whereas VLCFA length is determined by a lysine near the luminal

217 ALD and other peroxisomal diseases in which VLCFAs play a key role.

218 The barrier is associated mainly with VLCFA derivatives and less (if at all) with alicyclic wa

219 se in phospholipids, particularly those with VLCFA tails (PL-VLCFAs).