The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Assignment of Endogenous Substrates to Enzymes by Global Metabolite Profiling
Abstract
Enzymes regulate biological processes through the conversion of specific substrates to products. Therefore, of fundamental interest for every enzyme is the elucidation of its natural substrates. Here, we describe a general strategy for identifying endogenous substrates of enzymes by untargeted liquid chromatography-mass spectrometry (LC-MS) analysis of tissue metabolomes from wild-type and enzyme-inactivated organisms. We use this method to discover several brain lipids regulated by the mammalian enzyme fatty acid amide hydrolase (FAAH) in vivo, including known signaling molecules (e.g., the endogenous cannabinoid anandamide) and a novel family of nervous system-enriched natural products, the taurine-conjugated fatty acids. Remarkably, the relative hydrolytic activity that FAAH exhibited for lipid metabolites in vitro was not predictive of the identity of specific FAAH substrates in vivo. Thus, global metabolite profiling establishes unanticipated connections between the proteome and metabolome that enable assignment of an enzyme's unique biochemical functions in vivo.
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Cites
A SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES
Folch, J., Lees, M., & Stanley, G. H. S. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64849-5 · Cited by 65,189
A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION
Bligh, E. G., & Dyer, W. J. (1959) · Canadian Journal of Biochemistry and Physiology · doi:10.1139/o59-099 · Cited by 54,751
Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor
Devane, W. A., Hanuš, L., Breuer, A., Pertwee, R. G., Stevenson, L. A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A., & Mechoulam, R. (1992) · Science · doi:10.1126/science.1470919 · Cited by 5,633
Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides
Cravatt, B. F., Giang, D. K., Mayfield, S. P., Boger, D. L., Lerner, R. A., & Gilula, N. B. (1996) · Nature · doi:10.1038/384083a0 · Cited by 2,125
Self-citationBrain monoglyceride lipase participating in endocannabinoid inactivation
Dinh, T. P., Carpenter, D., Leslie, F. M., Freund, T. F., Katona, I., Sensi, S. L., Kathuria, S., & Piomelli, D. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.152334899 · Cited by 1,373
Cravatt, B. F., Demarest, K., Patricelli, M. P., Bracey, M. H., Giang, D. K., Martin, B. R., & Lichtman, A. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161191698 · Cited by 1,310
Self-citationGenome-Wide RNAi Analysis of Growth and Viability in Drosophila Cells
Boutros, M., Kiger, A. A., Armknecht, S., Kerr, K., Hild, M., Koch, B., Haas, S. A., Consortium, H. F. A., Paro, R., & Perrimon, N. (2004) · Science · doi:10.1126/science.1091266 · Cited by 702
Osuga, J.-I., Ishibashi, S., Oka, T., Yagyu, H., Tozawa, R., Fujimoto, A., Shionoiri, F., Yahagi, N., Kraemer, F. B., Tsutsumi, O., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.2.787 · Cited by 586
A nucleotide-flipping mechanism from the structure of human uracil–DNA glycosylase bound to DNA
Slupphaug, G., Mol, C. D., Kavli, B., Arvai, A. S., Krokan, H. E., & Tainer, J. A. (1996) · Nature · doi:10.1038/384087a0 · Cited by 581
Tolstikov, V. V., & Fiehn, O. (2002) · Analytical Biochemistry · doi:10.1006/abio.2001.5513 · Cited by 472
Functional analysis of secreted and transmembrane proteins critical to mouse development.
Mitchell, K. J., Pinson, K. I., Kelly, O. G., Brennan, J., Zupicich, J., Scherz, P., Leighton, P. A., Goodrich, L. V., Lu, X., Avery, B. J., et al. (2001) · Nature Genetics · doi:10.1038/90074 · Cited by 400
Fatty acid amide hydrolase: an emerging therapeutic target in the endocannabinoid system
Cravatt, B. F., & Lichtman, A. H. (2003) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(03)00079-6 · Cited by 302
Self-citationSystematic genome-wide screens of gene function
Carpenter, A. E., & Sabatini, D. M. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1248 · Cited by 298
Metabolic control analysis in drug discovery and disease
Cascante, M., Boros, L. G., Comin-Anduix, B., de Atauri, P., Centelles, J. J., & Lee, P. W.-N. (2002) · Nature Biotechnology · doi:10.1038/nbt0302-243 · Cited by 281
Lichtman, A. H., Hawkins, E. G., Griffin, G., & Cravatt, B. F. (2002) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.302.1.73 · Cited by 227
Self-citationActive site-directed protein regulation
Kobe, B., & Kemp, B. E. (1999) · Nature · doi:10.1038/46478 · Cited by 199
Clement, A. B., Hawkins, E. G., Lichtman, A. H., & Cravatt, B. F. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-09-03916.2003 · Cited by 188
Self-citationQuantification of Bioactive Acylethanolamides in Rat Plasma by Electrospray Mass Spectrometry
Giuffrida, A., Rodríguez de Fonseca, F., & Piomelli, D. (2000) · Analytical Biochemistry · doi:10.1006/abio.2000.4509 · Cited by 164
Patricelli, M. P., Lashuel, H. A., Giang, D. K., Kelly, J. W., & Cravatt, B. F. (1998) · Biochemistry · doi:10.1021/bi981733n · Cited by 150
Self-citationValidation of a new procedure to determine plasma fatty acid concentration and isotopic enrichment
Patterson, B. W., Zhao, G., Elias, N., Hachey, D. L., & Klein, S. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32435-4 · Cited by 125
Anandamide hydrolysis: a new target for anti-anxiety drugs?
Gaetani, S., Cuomo, V., & Piomelli, D. (2003) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2003.09.005 · Cited by 104
Visualization of biochemical networks in living cells
Remy, I., & Michnick, S. W. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.131216098 · Cited by 104
Pow, D. V., Sullivan, R., Reye, P., & Hermanussen, S. (2001) · Glia · doi:10.1002/glia.10026 · Cited by 103
Chemical species of lipids in bile.
Dw, H., & Carey, M. C. (1990) · PubMed · Cited by 73
Soo, E. C., Aubry, A. J., Logan, S. M., et al. (2003) · Analytical Chemistry · doi:10.1021/ac034875i · Cited by 70
Taurine‐Induced Long‐Lasting Enhancement of Synaptic Transmission in Mice: Role of Transporters
Sergeeva, O. A., Chepkova, A. N., Doreulee, N., et al. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.045864 · Cited by 68
Tappaz, M., Almarghini, K., & Kim, Q. (1994) · Advances in experimental medicine and biology · doi:10.1007/978-1-4899-1471-2_26 · Cited by 21
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Cravatt, B. F., Wright, A. T., & Kozarich, J. W. (2008) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.101304.124125 · Cited by 1,270
Self-citationMonoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis
Nomura, D. K., Long, J. Z., Niessen, S., Hoover, H. S., Ng, S.-W., & Cravatt, B. F. (2010) · Cell · doi:10.1016/j.cell.2009.11.027 · Cited by 1,002
Self-citationEnzymatic pathways that regulate endocannabinoid signaling in the nervous system
Ahn, K., McKinney, M. K., & Cravatt, B. F. (2008) · Chemical Reviews · doi:10.1021/cr0782067 · Cited by 529
Self-citationDiscovery and Characterization of a Highly Selective FAAH Inhibitor that Reduces Inflammatory Pain
Ahn, K., Johnson, D. S., Mileni, M., Beidler, D., Long, J. Z., McKinney, M. K., Weerapana, E., Sadagopan, N., Liimatta, M., Smith, S. E., et al. (2009) · Chemistry & Biology · doi:10.1016/j.chembiol.2009.02.013 · Cited by 439
Self-citationThe Metabolic Serine Hydrolases and Their Functions in Mammalian Physiology and Disease
Long, J. Z., & Cravatt, B. F. (2011) · Chemical Reviews · doi:10.1021/cr200075y · Cited by 425
Self-citation
Metadata
- Authors
- Saghatelian, A., Trauger, S. A., Want, E. J., Hawkins, E. G., Siuzdak, G., & Cravatt, B. F.
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2004-10-19
- Volume
- 43
- Issue
- 45
- Pages
- 14332-14339
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W2139846209
- Cited by
- 316
- References
- 27
- FWCI
- 5.58
- Type
- journal article
- Language
- en
- Open access
- closed
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