3-Hydroxy-3-methylglutaryl coenzyme A reductase localization in rat liver peroxisomes and microsomes of control and cholestyramine-treated animals: quantitative biochemical and immunoelectron microscopical analyses

doi:10.1083/jcb.103.3.875

This Article

	Full Text (PDF, 2894K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Keller, G. A.
	Articles by Krisans, S.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Keller, G. A.
	Articles by Krisans, S.


Social Bookmarking

	What's this?

ARTICLES

3-Hydroxy-3-methylglutaryl coenzyme A reductase localization in rat liver peroxisomes and microsomes of control and cholestyramine-treated animals: quantitative biochemical and immunoelectron microscopical analyses

GA Keller, M Pazirandeh and S Krisans

3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, a key regulatory enzyme involved in cholesterol biosynthesis, has recently been reported to be present in rat liver peroxisomes (Keller, G.A., M.C. Barton, D.J. Shapiro, and S.J. Singer, 1985, Proc. Natl. Acad. Sci. USA, 82:770-774). Immunoelectron labeling of ultrathin frozen sections of normal liver, using two monoclonal antibodies to purified rat liver microsomal HMG-CoA reductase, indicated that the enzyme is present in the matrix of peroxisomes. This study is a quantitative biochemical and immunoelectron microscopical analysis of HMG-CoA reductase in rat liver peroxisomes and microsomes of normal and cholestyramine-treated animals. Cholestyramine treatment produced a six- to sevenfold increase in the specific activity of peroxisomal HMG-CoA reductase, whereas the microsomal HMG-CoA reductase specific activity increased by about twofold. Using a computer program that calculates optimal linear combinations of marker enzymes, it was determined that between 20 and 30% of the total reductase activity was located in the peroxisomes of cholestyramine-treated animals. Less than 5% of the reductase activity was present in peroxisomes under control conditions. Quantitation of the immunoelectron microscopical data was in excellent agreement with the biochemical results. After cholestyramine treatment there was an eightfold increase in the density of gold particles per peroxisome, and we estimate about a threefold increase in the labeling of the ER.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Pena-Diaz, J., Montalvetti, A., Flores, C.-L., Constan, A., Hurtado-Guerrero, R., De Souza, W., Gancedo, C., Ruiz-Perez, L. M., Gonzalez-Pacanowska, D. (2004). Mitochondrial Localization of the Mevalonate Pathway Enzyme 3-Hydroxy-3-methyl-glutaryl-CoA Reductase in the Trypanosomatidae. Mol. Biol. Cell 15: 1356-1363 [Abstract] [Full Text]
Shechter, I., Dai, P., Huo, L., Guan, G. (2003). IDH1 gene transcription is sterol regulated and activated by SREBP-1a and SREBP-2 in human hepatoma HepG2 cells: evidence that IDH1 may regulate lipogenesis in hepatic cells. J. Lipid Res. 44: 2169-2180 [Abstract] [Full Text]
Breitling, R., Krisans, S. K. (2002). A second gene for peroxisomal HMG-CoA reductase? A genomic reassessment. J. Lipid Res. 43: 2031-2036 [Abstract] [Full Text]
Olivier, L. M., Kovacs, W., Masuda, K., Keller, G.-A., Krisans, S. K. (2000). Identification of peroxisomal targeting signals in cholesterol biosynthetic enzymes: AA-CoA thiolase, HMG-CoA synthase, MPPD, and FPP synthase. J. Lipid Res. 41: 1921-1935 [Abstract] [Full Text]
Geisbrecht, B. V., Gould, S. J. (1999). The Human PICD Gene Encodes a Cytoplasmic and Peroxisomal NADP+-dependent Isocitrate Dehydrogenase. J. Biol. Chem. 274: 30527-30533 [Abstract] [Full Text]
Fahimi, H. D., Baumgart, E. (1999). Current Cytochemical Techniques for the Investigation of Peroxisomes: A Review. J. Histochem. Cytochem. 47: 1219-1232 [Abstract] [Full Text]
Aboushadi, N., Engfelt, W. H., Paton, V. G., Krisans, S. K. (1999). Role of Peroxisomes in Isoprenoid Biosynthesis. J. Histochem. Cytochem. 47: 1127-1132 [Abstract] [Full Text]
Gupta, S. D., Mehan, R. S., Tansey, T. R., Chen, H.-T., Goping, G., Goldberg, I., Shechter, I. (1999). Differential binding of proteins to peroxisomes in rat hepatoma cells: unique association of enzymes involved in isoprenoid metabolism. J. Lipid Res. 40: 1572-1584 [Abstract] [Full Text]
Olivier, L. M., Chambliss, K. L., Gibson, K. M., Krisans, S. K. (1999). Characterization of phosphomevalonate kinase: chromosomal localization, regulation, and subcellular targeting. J. Lipid Res. 40: 672-679 [Abstract] [Full Text]
Engfelt, W. H., Masuda, K. R., Paton, V. G., Krisans, S. K. (1998). Splice donor site mutations in the 3-hydroxy-3-methylglutaryl coenzyme A reductase gene cause a deficiency of the endoplasmic reticulum 3-hydroxy-3-methylglutaryl coenzyme A reductase protein in UT2 cells. J. Lipid Res. 39: 2182-2191 [Abstract] [Full Text]
Aboushadi, N., Krisans, S. K. (1998). Analysis of isoprenoid biosynthesis in peroxisomal-deficient Pex2 CHO cell lines. J. Lipid Res. 39: 1781-1791 [Abstract] [Full Text]
Kanayama, N., Ueda, M., Atomi, H., Tanaka, A. (1998). Genetic Evaluation of Physiological Functions of Thiolase Isozymes in the n-Alkane-Assimilating Yeast Candida tropicalis. J. Bacteriol. 180: 690-698 [Abstract] [Full Text]
Engfelt, W. H., Shackelford, J. E., Aboushadi, N., Jessani, N., Masuda, K., Paton, V. G., Keller, G.-A., Krisans, S. K. (1997). Characterization of UT2 Cells. THE INDUCTION OF PEROXISOMAL 3-HYDROXY-3-METHYLGLUTARYL-COENZYME A REDUCTASE. J. Biol. Chem. 272: 24579-24587 [Abstract] [Full Text]
Paton, V. G., Shackelford, J. E., Krisans, S. K. (1997). Cloning and Subcellular Localization of Hamster and Rat Isopentenyl Diphosphate Dimethylallyl Diphosphate Isomerase. A PTS1 MOTIF TARGETS THE ENZYME TO PEROXISOMES. J. Biol. Chem. 272: 18945-18950 [Abstract] [Full Text]
Biardi, L., Krisans, S. K. (1996). Compartmentalization of Cholesterol Biosynthesis. J. Biol. Chem. 271: 1784-1788 [Abstract] [Full Text]
Wiemer, E.A.C., Terlecky, S.R., Nuttley, W.M., Subramani, S. (1995). Characterization of the Yeast and Human Receptors for the Carboxy-terminal Tripeptide Peroxisomal Targeting Signal. Cold Spring Harb Symp Quant Biol 60: 637-648 [Abstract]
Mcguire, E. J., Gray, R. H., De La Iglesia, F. A. (1992). Chemical Structure-Activity Relationships: Peroxisome Proliferation and Lipid Regulation in Rats. International Journal of Toxicology 11: 353-361 [Abstract]
Hunt, M. C., Solaas, K., Kase, B. F., Alexson, S. E. H. (2002). Characterization of an Acyl-CoA Thioesterase That Functions as a Major Regulator of Peroxisomal Lipid Metabolism. J. Biol. Chem. 277: 1128-1138 [Abstract] [Full Text]