Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1332347 (ADH)
 2,230 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kupffer cells are known to participate in the early events of liver injury involving lipid peroxidation. 4-Hydroxy-2,3-(E)-nonenal (4-HNE), a major aldehydic product of lipid peroxidation, has been shown to modulate numerous cellular systems and is implicated in the pathogenesis of chemically induced liver damage. The purpose of this study was to characterize the metabolic ability of Kupffer cells to detoxify 4-HNE through oxidative (aldehyde dehydrogenase; ALDH), reductive (alcohol dehydrogenase; ADH), and conjugative (glutathione S-transferase; GST) pathways. Aldehyde dehydrogenase and GST activity was observed, while ADH activity was not detectable in isolated Kupffer cells. Additionally, immunoblots demonstrated that Kupffer cells contain ALDH 1 and ALDH 2 isoforms as well as GST A4-4, P1-1, Ya, and Yb. The cytotoxicity of 4-HNE on Kupffer cells was assessed and the TD50 value of 32.5+/-2.2 microM for 4-HNE was determined. HPLC measurement of 4-HNE metabolism using suspensions of Kupffer cells incubated with 25 microLM 4-HNE indicated a loss of 4-HNE over the 30-min time period. Subsequent production of 4-hydroxy-2-nonenoic acid (HNA) suggested the involvement of the ALDH enzyme system and formation of the 4-HNE-glutathione conjugate implicated GST-mediated catalysis. The basal level of glutathione in Kupffer cells (1.33+/-0.3 nmol of glutathione per 10(6) cells) decreased significantly during incubation with 4-HNE concurrent with formation of the 4-HNE-glutathione conjugate. These data demonstrate that oxidative and conjugative pathways are primarily responsible for the metabolism of 4-HNE in Kupffer cells. However, this cell type is characterized by a relatively low capacity to metabolize 4-HNE in comparison to other liver cell types. Collectively, these data suggest that Kupffer cells are potentially vulnerable to the increased concentrations of 4-HNE occurring during oxidative stress.
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PMID:Metabolism of 4-hydroxynonenal by rat Kupffer cells. 1137 Jun 75

The genome of Natronomonas pharaonis encodes genes annotated as alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase (ALDH; EC 1.2.1.3), enzymes involved in alcohol metabolism. These genes (adh and aldH2) occur in a single copy on the chromosome. We have studied the role of these genes in ethanol metabolism in N. pharaonis. Reverse transcription-PCR analysis showed that the aldH2 gene was inducible by ethanol, but the adh gene was transcribed both in the presence and absence of ethanol. The gene encoding for ALDH of N. pharaonis (NpALDH) was cloned into a pET41a vector containing a glutathione S-transferase tag, expressed in Escherichia coli and purified by glutathione sepharose affinity chromatography. The GST-NpALDH fusion protein was cleaved by bovine enterokinase and the target enzyme showed a molecular mass of approximately 60 kDa by SDS-PAGE. The enzyme was thermophilic and alkaliphilic, the optimal temperature and pH being 60 degrees C and 8.0, respectively. NpALDH was salt independent, being most active at 0.25 M NaCl or KCl.
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PMID:Aldehyde dehydrogenase of the haloalkaliphilic archaeon Natronomonas pharaonis and its function in ethanol metabolism. 1876 68