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Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function
Open accessAbstract
Gene targeting in mice was used to investigate the unknown function of Scp2, encoding sterol carrier protein-2 (SCP2; a peroxisomal lipid carrier) and sterol carrier protein-x (SCPx; a fusion protein between SCP2 and a peroxisomal thiolase). Complete deficiency of SCP2 and SCPx was associated with marked alterations in gene expression, peroxisome proliferation, hypolipidemia, impaired body weight control, and neuropathy. Along with these abnormalities, catabolism of methyl-branched fatty acyl CoAs was impaired. The defect became evident from up to 10-fold accumulation of the tetramethyl-branched fatty acid phytanic acid in Scp2(-/-) mice. Further characterization supported that the gene disruption led to inefficient import of phytanoyl-CoA into peroxisomes and to defective thiolytic cleavage of 3-ketopristanoyl-CoA. These results corresponded to high-affinity binding of phytanoyl-CoA to the recombinant rat SCP2 protein, as well as high 3-ketopristanoyl-CoA thiolase activity of the recombinant rat SCPx protein.
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Cites
Spontaneous Hypercholesterolemia and Arterial Lesions in Mice Lacking Apolipoprotein E
Zhang, S. H., Reddick, R. L., Piedrahita, J. A., & Maeda, N. (1992) · Science · doi:10.1126/science.1411543 · Cited by 2,237
Self-citationLeenders, F., Tesdorpf, J. G., Markus, M., Engel, T., Seedorf, U., & Adamski, J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.10.5438 · Cited by 116
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Cited by
The Enzymes, Regulation, and Genetics of Bile Acid Synthesis
Russell, D. W. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161712 · Cited by 2,069
Biochemistry of mammalian peroxisomes revisited
Wanders, R. J. A., & Waterham, H. R. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133329 · Cited by 995
Self-citationCholesterol homeostasis and function in neurons of the central nervous system
Pfrieger, F. W. (2003) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-3018-7 · Cited by 453
Rone, M. B., Fan, J., & Papadopoulos, V. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.03.001 · Cited by 399
Wanders, R. J. A., Waterham, H. R., & Ferdinandusse, S. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2015.00083 · Cited by 366
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Metadata
- Authors
- Seedorf, U., Raabe, M., Ellinghaus, P., Kannenberg, F., Fobker, M., Engel, T., Denis, S., Wouters, F., Wirtz, K. W. A., Wanders, R. J. A., Maeda, N., & Assmann, G.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1998-04-15
- Volume
- 12
- Issue
- 8
- Pages
- 1189-1201
- ISSN
- 0890-9369 (ISSN-L)
- OpenAlex
- W4301052166
- Cited by
- 270
- References
- 2
- Type
- posted content
- Language
- en
- Open access
- diamond
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- CoChat. (2026). Citation check: Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function. https://app.cochat.ai/papers/10.1101/gad.12.8.1189
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- Seedorf, U., Raabe, M., Ellinghaus, P., Kannenberg, F., Fobker, M., Engel, T., Denis, S., Wouters, F., Wirtz, K. W. A., Wanders, R. J. A., Maeda, N., & Assmann, G. (1998). Defective peroxisomal catabolism of branched fatty acyl coenzyme A in mice lacking the sterol carrier protein-2/sterol carrier protein-x gene function. Genes & Development. https://doi.org/10.1101/gad.12.8.1189
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