Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0220723 (PCA)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of administration of galactosamine (GalN) and glucosamine (GlcN) on the levels of UDP-sugars and hexose monophosphates in rat livers were studied by a variety of 31P NMR methods. The flux of metabolites in the liver was monitored by in vivo NMR and showed elevated levels of UDP-sugars, and even greater increases in resonances at 4.6 ppm for GlcN treatment and at 2.0 ppm for GalN treatment. The individual compounds corresponding to these changes were identified in PCA liver extracts by 31P-[1H] two-dimensional relay spectroscopy with a HOHAHA-type 1H spin-lock. This method of transferring proton magnetization allows for nearly all of the proton chemical shifts to be observed for the hexose moiety of a UDP-sugar present in a complex mixture. The UDP-sugars in the extracts from treated rats were predominantly UDP-hexosamines. Relay spectra were also used to determine that GalN-1-P was the major component (16.0 mumol/g of liver) of the GalN-treated liver, while both alpha and beta anomers of GlcNAc-6-P were readily identified as the major hexose monophosphates in the GlcN experiment. Spectra from the 1H dimension of relay experiments conducted on extracts were nearly superimposable on relay spectra obtained under the same conditions for mixtures of standard compounds of known structure. UDP-GlcN and UDP-GalN were not commercially available, but their presence was established in the extracts after GalN treatment by obtaining relay spectra for a mixture of the compounds produced in situ enzymatically, without purification.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Uridine diphospho sugars and related hexose phosphates in the liver of hexosamine-treated rats: identification using 31P-[1H] two-dimensional NMR with HOHAHA relay. 235 May 39

The relative importance of technical versus bio-logical variation in UPLC-MS liver metabolic profiling studies was assessed on liver samples collected as part of an in vivo hepatotoxicity study. Biological variability within and between two treatment groups (three rats treated with galactosamine and three with galactosamine+uridine) was compared with sampling/extraction variability (three portions extracted from each rat liver section) and UPLC-MS platform variability (triplicate injections of each extract) for aqueous and organic extracts. The impact of scaling on error measurement was investigated on replicate injections of a quality control sample, and consequently started log-transformation was used to stabilize the variance across the ion intensity range. For aqueous extracts, technical variability was two to four times lower than within group interanimal variability. Similar results were obtained for organic extracts for the galactosamine group, sampling/extraction variability being more elevated in the galactosamine+uridine group. For both extract types, differences between treatment groups were the principal source of observed variation, and triplicate injections clustered closely in PCA plots and in HCA dendrograms, indicating small instrument variability compared to observed biological variation. This protocol can be applied to investigate differences in liver metabolic profiles between animal groups in toxicology studies and clinical investigations of liver disease.
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PMID:Technical and biological variation in UPLC-MS-based untargeted metabolic profiling of liver extracts: application in an experimental toxicity study on galactosamine. 2124 Oct 57