- M.S., Ph.D. Technical University Berlin
ResearchBeta Oxidation of Fatty Acids
Fatty acids are degraded by ß-oxidation in both mitochondria and peroxisomes of animal cells. Although the two organelle-specific processes are well-established, important questions about the pathways and their cooperation, the enzymes and their supramolecular organizations, and the regulation of these processes remain unanswered. It is the long-term goal of this research group to resolve these questions with the aim of providing a comprehensive and detailed view of this vital area of mammalian metabolism. The focus of our current research effort is the ß-oxidation of unsaturated and polyunsaturated fatty acids with an emphasis on reactions and reaction sequences that involve preexisting double bonds. Our experimental approaches include (1) metabolic studies with cellular extracts, isolated mitochondria, peroxisomes, and isolated cells and (2) investigations of ß-oxidation enzymes that require their purifications, their molecular cloning and mutagenesis to carry out metabolic and mechanistic studies of these enzymes. Simultaneously an investigation continues that assesses the impact of the supramolecular organization of ß-oxidation enzymes on the regulation of this process in mitochondria. These studies are expected to provide a better understanding of the dynamics of fatty acid oxidation in normal and diseased mammals.
Liang, X., Le, W., Zhang, D. and Schulz, H. 2001. Impact of the Intramitochondrial Enzyme Organization on Fatty Acid Oxidation. Biochem. Soc. Trans. 29, 279-282.
Zhang, D., Liang, X., He, X.-Y., Alipui, O.D., Yang, S.-Y. and Schulz, H. 2001. 3,5,2,4
-Dienoyl-CoA Isomerase Is a Multifunctional Isomerase: A Structural and Mechanistic Study. J. Biol. Chem. 276, 13622-13627.
Zhang, D., Yu, W., Geisbrecht, B.V., Gould, S.J., Sprecher, H. and Schulz, H. 2002. Functional Characterization of 3,2
-Enoyl-CoA Isomerases from Rat Liver. J. Biol. Chem. 277, 9127-9132.
Schulz, H. 2002. Oxidation of Fatty Acids in Eukaryotes. In Biochemistry of Lipids, Lipoproteins and Membranes (Vance, D., and Vance, J., eds.) Elsevier, Amsterdam, pp. 127-150.
Ren, Y. and Schulz, H. 2003 Metabolic Functions of the Two Pathways of Oleate ß-Oxidation. Double Bond Metabolism During the ß-Oxidation of Oleic Acid in Rat Heart Mitochondria. J. Biol. Chem. 278, 111-116.
Hubbard, P.A., Liang, X., Schulz, H. and Kim, J.-J.P. 2003. The Crystal Structure and Catalytic Mechanism of E. coli 2,4-Dienoyl-CoA Reductase. J. Biol. Chem. 278, 37553-37560.
Ren, Y., Aguirre, J., Ntamack, A.G., Chu, C. and Schulz, H. 2004. An Alternative Pathway of Oleate ß-Oxidation in Escherichia coli Involving Hydrolysis of a Dead-end Intermediate by a Thioesterase. J. Biol. Chem. 279, 11042-11050.