Project description:The hepatic endoplasmic reticulum contains a series of enzymes that oxidize and conjugate lipid and steroids. Together, these enzymes form a molecular machine that plays key roles in the metabolism of both endogenous and xenobiotic compounds. To characterize this molecular machine, we used quantitative proteomics to assess the frequency of occurrence of detected peptides within each primary sequence, leading to the assessment of the relative abundances of 137 of these proteins. These 137 proteins include over 38 different cytochrome P450s, 11 glucuronosyltransferases, and 9 carboxylesterases. Our sensitive approach was able to detect P450 allelic isoforms which differ by only a single amino acid and clearly resolved 4 splice variants of the glucuronosyltransferases. We identified a cytosolically-exposed DID motif for 3 cytochrome P450s that were located with high abundance in the Golgi apparatus as well the lack of a C-terminal HXEL motif for the sole carboxylesterase highly abundant in the Golgi. Using gene expression microarrays, we also characterized the hepatic transcriptome, and a comparison of proteomics and transcriptomics indicated a requirement for both technologies in order to provide insight into protein families of drug detoxification. In this way, a major hurdle of hepatotoxicity related to drug development may be overcome. Keywords: steady-state mRNA levels

2009-11-24 | GSE9226 | GEO

Shining a Light on Phenotypic Drug Discovery.

Project description: Not available

| S-EPMC8121186 | biostudies-literature

Large-scale causal discovery using interventional data sheds light on gene network structure in k562 cells.

Project description: Not available

| S-EPMC12579002 | biostudies-literature

Cryo-EM structures of CRAF/MEK1/14-3-3 complexes in autoinhibited and open-monomer states reveal features of RAF regulation

Project description: Not available

| S-EPMC12402067 | biostudies-literature

Large-scale causal discovery using interventional data sheds light on the regulatory network architecture of blood traits.

Project description: Not available