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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Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor
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Self-citationBrain monoglyceride lipase participating in endocannabinoid inactivation
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Self-citationGenome-Wide RNAi Analysis of Growth and Viability in Drosophila Cells
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A nucleotide-flipping mechanism from the structure of human uracil–DNA glycosylase bound to DNA
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Cited by
Activity-Based Protein Profiling: From Enzyme Chemistry to Proteomic Chemistry
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
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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-citationChemical Probes of Endocannabinoid Metabolism
Blankman, J. L., & Cravatt, B. F. (2013) · Pharmacological Reviews · doi:10.1124/pr.112.006387 · Cited by 327
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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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