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

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

7 VLCFA beta-oxidation but does not accumulate VLCFA.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

43 n that contain enzymes capable of activating VLCFA.

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

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

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

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

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

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

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

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

52 hway controls Elo2 phosphorylation state and VLCFA synthesis.

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

54 ine species containing unsaturated LCFAs and VLCFAs.

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

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

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

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

59 sm that generates the repertoire of cellular VLCFAs.

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

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

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

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

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

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

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

67 atment of diseases characterized by elevated VLCFA levels.

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

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

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

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

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

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

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

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

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

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

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

79 The full VLCFA biosynthetic machinery and how this machinery gene

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

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

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

83 1-knockdown and the subsequent alteration in VLCFA metabolism in human U87 astrocytes and rat B12 oli

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

106 chondrial abnormalities, and accumulation of VLCFAs.

107 tracted from canola is essentially devoid of VLCFAs.

108 ed oil composition to contain high levels of VLCFAs.

109 s accumulate substantially reduced levels of VLCFAs.

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

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

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

113 her members of the translation initiation or VLCFA pathways.

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

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

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

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

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

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

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

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

122 Plasma VLCFA concentrations decreased by 55% and remained sligh

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

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

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

126 novel synthases with correspondingly shorter VLCFA outputs.

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

128 very slowly growing) and do synthesize some VLCFA.

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

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

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

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

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

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

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

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

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

138 revealed that the mutant lipid A lacked the VLCFA.

139 henotypes of an acpXL mutant which lacks the VLCFA.

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

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

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

143 rane for subsequent re-esterification of the VLCFAs.

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

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

146 Whereas VLCFA synthesis is essential for viability, the ybr159De

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

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