ライフサイエンスコーパス: VLCAD

1 VLCAD also possesses an additional 180 residues in the C

2 VLCAD and DLG4 are arranged in a head-to-head orientatio

3 VLCAD associates with the inner mitochondrial membrane a

4 VLCAD deficiency is among the more common defects of mit

5 VLCAD(-/-) mice had milder fatty change in liver and hea

6 RNA blot analysis and VLCAD enzyme assays showed a severe reduction in VLCAD m

7 spite the overlap of their 5' ends, DLG4 and VLCAD exhibit peak mRNA expression in different tissues,

8 ires and dams heterozygous for both LCAD and VLCAD mutations.

9 e results for liver were most informative as VLCAD(-/-) mice had a reduction in activity toward palmi

10 Suppression of FAO at VLCAD triggered an increase in pyruvate dehydrogenase ac

11 produce an inborn error of metabolism called VLCAD deficiency that can lead to severe pathophysiologi

12 rs, we generated mice with VLCAD deficiency (VLCAD(-/-)) and compared their pathologic and biochemica

13 ry-long-chain acyl-coenzyme A dehydrogenase (VLCAD)-deficient mice by homologous recombination to def

14 ding very long chain acyl-CoA dehydrogenase (VLCAD) and postsynaptic density protein 95 (PSD-95) is a

15 Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the first step in the beta-oxidation sp

16 Very long acyl-CoA dehydrogenase (VLCAD) deficiency is a genetic pediatric disorder presen

17 Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an inherited disorder of mitochondr

18 Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is the most common defect of mitochond

19 have very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, none have been documented with long-c

20 the very-long-chain acyl-CoA dehydrogenase (VLCAD) enzyme, which exacerbates accumulation of LCFAs a

21 Very-long-chain acyl-CoA dehydrogenase (VLCAD) is a major enzyme catalysing the first step in mi

22 Very-long-chain acyl-CoA dehydrogenase (VLCAD) is a member of the family of acyl-CoA dehydrogena

23 Very long-chain acyl-CoA dehydrogenase (VLCAD) is an inner mitochondrial membrane enzyme that ca

24 Very long chain acyl-CoA dehydrogenase (VLCAD; ACADVL) was found to be overexpressed and critica

25 Interestingly, the human genes encoding VLCAD (ACADVL) and PSD-95 (DLG4) are adjacently located

26 lysis showed that the beta-oxidation enzyme, VLCAD, is cleaved by calpain-3 in vitro, but we were not

27 elevated in bile, blood and serum of fasted VLCAD(-/-) mice, whereas abnormally elevated C(12) and C

28 hus, our data support a structural basis for VLCAD deficiency in patients with discrete mutations in

29 ther ACADs, which are soluble homotetramers, VLCAD is a homodimer associated with the mitochondrial m

30 Point mutations in human VLCAD can produce an inborn error of metabolism called V

31 ane interaction defect of full-length, human VLCAD bearing the clinically-observed mutations, A450P o

32 Mutations in the human VLCAD gene are heterogeneous.

33 In VLCAD, these residues are glycines (Gly-175 and Gly-178)

34 etics and redox homeostasis were assessed in VLCAD-deficient fibroblasts, and several protective comp

35 was associated with an 8-17-fold increase in VLCAD-specific activity and concomitant correction of ac

36 D enzyme assays showed a severe reduction in VLCAD mRNA in patients with frame-shift or splice-site m

37 Interestingly, VLCAD and DLG4 genes do not overlap in the mouse or Dros

38 Progeny with the combined LCAD(+/+)//VLCAD(+/-) genotype were over-represented in offspring f

39 ast, no live mice with a compound LCAD(-/-)//VLCAD(-/-) genotype were detected.

40 with a more severe defect in FAO (LCAD(-/-); VLCAD(+/-)) in addition to a validated mouse model (LCAD

41 ition to a validated mouse model (LCAD(-/-); VLCAD(+/+)) and compared them with wild-type (WT) mice.

42 drop in body temperature in unfed LCAD(-/-); VLCAD(+/+) mice compared with WT body temperature.

43 reated HepG2 cells revealed that the minimal VLCAD promoter is able to up-regulate VLCAD expression i

44 of both promoters and abolished the minimal VLCAD promoter's response to DEHP treatment.

45 t fibroblasts, which express distinct mutant VLCAD protein and exhibit deficient fatty acid beta-oxid

46 ion of VLCAD deficiency by increasing mutant VLCAD enzymatic activity.

47 part of DLG4 exon 1 and the entire exon 1 of VLCAD including 62 bp of protein coding sequence.

48 However, the activity of VLCAD was decreased in C3KO mitochondrial fractions comp

49 esent a novel strategy for the correction of VLCAD deficiency by increasing mutant VLCAD enzymatic ac

50 these results demonstrate the importance of VLCAD in AML cell biology and highlight a novel metaboli

51 attenuation or pharmacological inhibition of VLCAD hindered mitochondrial respiration and FAO contrib

52 ine induced site-specific S-nitrosylation of VLCAD mutants at cysteine residue 237.

53 CM is the most common clinical phenotype of VLCAD deficiency.

54 ire approximately 270-bp minimal promoter of VLCAD.

55 -uncharacterized C-terminal domain region of VLCAD cause enzymatic deficiency by an incompletely defi

56 the N-terminal approximately 400 residues of VLCAD is similar to that of the soluble ACADs including

57 on analysis and the overlapping structure of VLCAD and DLG4 was clarified.

58 We have determined the crystal structure of VLCAD complexed with myristoyl-CoA, obtained by co-cryst

59 Treatment of VLCAD-deficient fibroblasts, which express distinct muta

60 ction and signaling pathways in a variety of VLCAD-deficient fibroblasts.

61 gene, discs-large-related 4 (DLG4), overlaps VLCAD and is transcribed in the opposite direction.

62 inimal VLCAD promoter is able to up-regulate VLCAD expression in response to DEHP treatment.

63 vitro, but we were not able to confirm that VLCAD is an in vivo substrate for calpain-3.

64 We found that VLCAD-deficient hearts have microvesicular lipid accumul

65 o the eukaryotic domain: one resulted in the VLCAD and ACAD9 paralogs and another in the ACAD10 and A

66 The transcription start site of the VLCAD gene was determined by primer extension analysis a

67 During analysis of the VLCAD promoter, we discovered that another gene, discs-l

68 lysis revealed 21 different mutations on the VLCAD gene in 18 patients.

69 didate compounds to further develop to treat VLCAD-deficient patients.

70 allows us to gain insight into how a variant VLCAD genotype results in a clinical phenotype.

71 oxidation disorders, we generated mice with VLCAD deficiency (VLCAD(-/-)) and compared their patholo

72 We conclude that mice with VLCAD deficiency have altered expression of a variety of

73 Patients with VLCAD deficiency may present with hypoglycemia, hepatome