ライフサイエンスコーパス: MCAD

1 MCAD-deficiency is the most common inborn error of fatty

2 rst (fast) step involved the formation of an MCAD-IACoA collision complex in which the electronic str

3 f ERRalpha paralleled that of PGC-1alpha and MCAD.

4 pha paralleled NRRE-1 binding activities and MCAD expression during brown adipocyte differentiation,

5 een either human or P. denitrificans ETF and MCAD demonstrates that the human ETF functions optimally

6 inal adipose tissue, CL-upregulated FASN and MCAD in distinct cell populations: high MCAD expression

7 ures of the product analogue in its free and MCAD-bound forms have been characterized by Raman differ

8 es in mitochondrial beta-oxidation rates and MCAD expression.

9 This binding event attenuates MCAD activity and inhibits fatty acid oxidation, thereby

10 , HCV infection significantly decreased both MCAD and SCAD expression, which is controlled by FoxA2.

11 tty acid and ATP metabolism (i.e., FAT/CD36, MCAD, and COX I).

12 normalized PGC-1alpha, PPARalpha, FAT/CD36, MCAD, Tfam, and COX I after T-H.

13 ed to be the catalytic base in medium-chain (MCAD) and short-chain acyl-CoA dehydrogenases and is con

14 ed by the C1 and C3 HD carbons in the HD-CoA/MCAD complex is proposed to arise from the ring current

15 medium-chain acyl coenzyme A dehydrogenase (MCAD) and short-chain acyl coenzyme A dehydrogenase (SCA

16 medium-chain acyl coenzyme A dehydrogenase (MCAD), a nuclearly encoded mitochondrial fatty acid beta

17 medium chain acyl-coenzyme A dehydrogenase (MCAD), requires cis-acting elements located within the p

18 medium chain acyl-coenzyme A dehydrogenase (MCAD; 1.8+/-0.1 versus 2.9+/-0.3 micromol x min(-1) x g(

19 Medium-chain acyl-coenzyme A dehydrogenase (MCAD; mouse gene Acadm; human gene ACADM) catalyzes the

20 ld-type medium-chain acyl-CoA dehydrogenase (MCAD) and two of its mutant forms.

21 kidney medium chain acyl-CoA dehydrogenase (MCAD) by isothermal titration microcalorimetry under a v

22 Medium-chain acyl-CoA dehydrogenase (MCAD) catalyzes the flavin-dependent oxidation of fatty

23 ties of medium-chain acyl-CoA dehydrogenase (MCAD) from pig kidney.

24 376, of medium-chain acyl-CoA dehydrogenase (MCAD) has been known to abstract the alpha-proton from a

25 SN) and medium chain acyl-CoA dehydrogenase (MCAD) protein within the same cells in classic brown and

26 tion in medium chain acyl-CoA dehydrogenase (MCAD), creates a complementary cavity of 18 A(3) dimensi

27 porcine medium chain acyl-CoA dehydrogenase (MCAD), Glu254 in human isovaleryl-CoA dehydrogenase (IVD

28 r) with medium chain acyl-CoA dehydrogenase (MCAD), were essentially identical, suggesting that the p

29 ncoding medium-chain acyl-CoA dehydrogenase (MCAD), which catalyzes the initial step in mitochondrial

30 n liver medium chain acyl-CoA dehydrogenase (MCAD)-catalyzed reaction proceeds via abstraction of an

31 n liver medium-chain acyl-CoA dehydrogenase (MCAD)-catalyzed reaction, we became interested in deline

32 cluding medium-chain acyl-CoA dehydrogenase (MCAD).

33 ts with medium-chain acyl-CoA dehydrogenase (MCAD).

34 and pig medium-chain acyl-CoA dehydrogenase (MCAD).

35 n liver medium-chain acyl-CoA dehydrogenase (MCAD).

36 kidney medium-chain acyl-CoA dehydrogenase (MCAD).

37 g human medium-chain acyl-CoA dehydrogenase (MCAD, which catalyzes a rate-limiting step in the FAO cy

38 The levels of mRNA encoding MCAD and several other beta-oxidation cycle enzymes were

39 neonatal cardiac mycoytes induced endogenous MCAD expression.

40 lytic base (pK(a,ox) approximately 6.5, free MCAD), it has little effect on the pK of Glu99 (pK(a,ox)

41 K of Glu99 (pK(a,ox) approximately 7.5, free MCAD).

42 ociation constant of MCAD +octenoyl-CoA <==> MCAD-octenoyl-CoA yields a pKa for the free enzyme of 6.

43 ation mixture of MCAD and IACoA ([IACoA] >> [MCAD] > Kd) increases from 12 to 35 degrees C, the resul

44 and MCAD in distinct cell populations: high MCAD expression occurred in multilocular adipocytes that

45 Mice transgenic for human MCAD gene promoter fragments fused to a chloramphenicol

46 We have shown previously that the human MCAD gene promoter contains a pleiotropic element (nucle

47 pK of 9.2 determined for Glu376 in the human MCAD.4-thia-octenoyl-CoA complex.

48 In MCAD, Gln-95 and Glu-99 form the base of the substrate b

49 lated AST-elevation indicated cell damage in MCAD-deficiency.

50 ht of structural-functional relationships in MCAD catalysis.

51 uction of endogenous target genes, including MCAD and GLUT4, is largely repressed by GCN5.

52 Inherited MCAD deficiency is an autosomal recessive disorder that

53 or the binding of octenoyl-CoA to pig kidney MCAD (which is believed to be structurally identical to

54 r Glu376 and Glu99 in the reduced pig kidney MCAD.HD-CoA complex, 9.8 and 8.6, respectively, suggest

55 Expression of the full-length MCAD promoter-chloramphenicol acetyltransferase transgen

56 rown adipose tissue, tissues with high-level MCAD expression.

57 but for patients with chronic diseases like MCAD as well.

58 to be structurally identical to human liver MCAD) is only -0.37 kcal mol-1 K-1 prompt us to question

59 oA, with the recombinant form of human liver MCAD.

60 f the MCADCAT.371 transgene paralleled mouse MCAD mRNA levels.

61 genetically engineered to overexpress murine MCAD markedly suppresses tumor growth.

62 estion that the carboxyl group of Glu-376 of MCAD is intimately involved in modulating the microscopi

63 RXRalpha and the expression and activity of MCAD.

64 Expression of transgenes comprised of MCAD gene promoter fragments fused to chloramphenicol ac

65 pH dependence of the association constant of MCAD +octenoyl-CoA <==> MCAD-octenoyl-CoA yields a pKa f

66 y unit shown previously to confer control of MCAD gene transcription during cardiac development.

67 Consistently, the protein expression of MCAD and of RXRalpha were significantly reduced by 38% i

68 HCV-infected cells rescued the expression of MCAD and SCAD.

69 ro-AST formation is not a special feature of MCAD-deficiency but rather a non-specific, coincidental

70 mol(-1) K(-1), suggesting that formation of MCAD-octenoyl-CoA is enthalpically driven.

71 the temperature of the incubation mixture of MCAD and IACoA ([IACoA] >> [MCAD] > Kd) increases from 1

72 ry (n) of 0.89 mole of octenoyl-CoA/(mole of MCAD subunit), delta G = -8.75 kcal/mol, delta H = -10.3

73 ic strength dependencies for the reaction of MCAD with the two ETFs.

74 ferase reporter confirmed that repression of MCAD gene expression in the hypertrophied ventricle occu

75 th, and temperature on the thermodynamics of MCAD-octenoyl-CoA interaction.

76 (pK(a,ox) approximately 7.4) in the oxidized MCAD.HD-CoA complex indicate that while binding of the C

77 duct analogue that binds tightly to oxidized MCAD (K(dox) = 3.5 +/- 0.1 microM, pH 7.6) and elicits a

78 A), a product analogue, with recombinant pig MCAD (pMCAD) has been studied using (13)C NMR and (1)H-(

79 rotein expression of ACC-1, FASN, PPARalpha, MCAD, ADIPOR-1, and mCPT-1.

80 Therefore, targeting the caspase-1/PPARgamma/MCAD pathway might be a promising therapeutic approach t

81 ction (consumption) of 0.52 +/- 0.15 proton/(MCAD subunit) from the buffer media.

82 hepatic expression of key PPAR-alpha target (MCAD, mitochondrial HMG CoA synthase, ACO, CYP4A3) and o

83 red for the transcriptional induction of the MCAD gene during brown adipocyte differentiation.

84 ements in the transcriptional control of the MCAD gene in vivo.

85 d within the proximal promoter region of the MCAD gene.

86 epressed the transcriptional activity of the MCAD promoter.

87 egrees C, the resultant spectral peak of the MCAD-IACoA complex (lambda max = 417 nm) decreases.

88 he spectral changes, binding constant of the MCAD-IACoA complex, and the rate constants for the conve

89 thalpies, we discerned that formation of the MCAD-octenoyl-CoA complex, at pH 7.6, accompanies abstra

90 The midpoint potential of the MCAD.HD-CoA complex exhibits a pH dependence that is con

91 ntaining an estrogen response element or the MCAD gene promoter by ERRalpha and the related isoform E

92 enone fragment is polarized upon binding to MCAD such that the electron density at the C3 and C1 car

93 These results suggest that, upon binding to MCAD, HD-CoA is selectively polarized such that partial

94 s are narrower when the ligands are bound to MCAD than when they are free in the protein solution.

95 n the NMR and Raman data for HD-CoA bound to MCAD, (13)C NMR spectra have been obtained for HD-CoA bo

96 the fact that the binding of octenoyl-CoA to MCAD is primarily dominated by the hydrophobic forces.

97 data for the binding of 2-azaoctanoyl-CoA to MCAD revealed that the overall interaction proceeds via

98 acetoacetyl-CoA when bound as an enolate to MCAD and enoyl-CoA hydratase and is used to rationalize

99 rimetric studies for the binding of IACoA to MCAD reveal that the overall binding energy at 25 degree

100 tic consequences for the binding of IACoA to MCAD, the apparent similarity between the van't Hoff and

101 s of the two reaction steps in the wild-type MCAD demonstrate that the reaction proceeds by a stepwis

102 We report a female patient with MCAD-deficiency in whom at the age of 11 years isolated

103 horetic mobility-shift assays performed with MCAD promoter fragments and nuclear protein extracts pre

104 Transient-transfection studies with MCAD promoter-luciferase constructs containing normal or