Mitochondrial long chain fatty acid β-oxidation in man and mouse

被引：107

作者：

Chegary, Malika ^{[1
,2
]}

Brinke, Heleen Te ^{[1
]}

Ruiter, Jos P. N. ^{[1
]}

Wijburg, Frits A. ^{[2
]}

Stoll, Maria S. K. ^{[3
]}

Minkler, Paul E. ^{[3
]}

van Weeghel, Michel ^{[1
]}

Schulz, Horst ^{[5
,6
]}

Hoppel, Charles L. ^{[3
,4
]}

Wanders, Ronald J. A. ^{[1
,2
]}

Houten, Sander M. ^{[1
,2
]}

机构：

[1] Univ Amsterdam, Acad Med Ctr, Dept Clin Chem, Lab Genet Metab Dis,Emma Childrens Hosp, NL-1105 AZ Amsterdam, Netherlands

[2] Univ Amsterdam, Acad Med Ctr, Dept Pediat, Emma Childrens Hosp, NL-1105 AZ Amsterdam, Netherlands

[3] Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA

[4] Case Western Reserve Univ, Sch Med, Dept Med, Cleveland, OH 44106 USA

[5] City Coll, Dept Chem, New York, NY USA

[6] CUNY, Grad Ctr, New York, NY USA

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS | 2009年 / 1791卷 / 08期

关键词：

Cellular metabolism; Inborn errors of metabolism; Fatty acid oxidation; Mouse model; Long chain acyl-CoA dehydrogenase; Very long chain acyl-CoA dehydrogenase; ACYL-COA DEHYDROGENASE; COENZYME-A DEHYDROGENASE; ISOFORM DEFICIENCY; MASS-SPECTROMETRY; SUDDEN-DEATH; CARNITINE; FIBROBLASTS; DISORDERS; MICE; DEFECTS;

D O I：

10.1016/j.bbalip.2009.05.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Several mouse models for mitochondrial fatty acid P-oxidation (FAO) defects have been developed. So far, these models have contributed little to our current understanding of the pathophysiology. The objective of this study was to explore differences between murine and human FAO. Using a combination of analytical, biochemical and molecular methods, we compared fibroblasts of long chain acyl-CoA dehydrogenase knockout (LCAD(-/-)), very long chain acyl-CoA dehydrogenase knockout (VLCAD(-/-)) and wild type mice with fibroblasts of VLCAD-deficient patients and human controls. We show that in mice, LCAD and VLCAD have overlapping and distinct roles in FAO. The absence of VLCAD is apparently fully compensated, whereas LCAD deficiency is not. LCAD plays an essential role in the oxidation of unsaturated fatty acids such as oleic acid, but seems redundant in the oxidation of saturated fatty acids. In strong contrast, LCAD is neither detectable at the mRNA level nor at the protein level in men, making VLCAD indispensable in FAO. Our findings open new avenues to employ the existing mouse models to study the pathophysiology of human FAO defects. (C) 2009 Elsevier B.V. All rights reserved.

引用

页码：806 / 815

页数：10

共 39 条

[1] PURIFICATION OF HUMAN VERY-LONG-CHAIN ACYL-COENZYME-A DEHYDROGENASE AND CHARACTERIZATION OF ITS DEFICIENCY IN 7 PATIENTS [J].