Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The route of l-threonine degradation was studied in four strains of the genus Pseudomonas able to grow on the amino acid and selected because of their high l-threonine aldolase activity. Growth and manometric results were consistent with the cleavage of l-threonine to acetaldehyde+glycine and their metabolism via acetate and serine respectively. 2. l-Threonine aldolases in these bacteria exhibited pH optima in the range 8.0-8.7 and K(m) values for the substrate of 5-10mm. Extracts exhibited comparable allo-l-threonine aldolase activities, K(m) values for this substrate being 14.5-38.5mm depending on the bacterium. Both activities were essentially constitutive. Similar activity ratios in extracts, independent of growth conditions, suggested a single enzyme. The isolate Pseudomonas D2 (N.C.I.B. 11097) represents the best source of the enzyme known. 3. Extracts of all the l-threonine-grown pseudomonads also possessed a CoA-independent aldehyde dehydrogenase, the synthesis of which was induced, and a reversible alcohol dehydrogenase. The high acetaldehyde reductase activity of most extracts possibly resulted in the underestimation of acetaldehyde dehydrogenase. 4. l-Serine dehydratase formation was induced by growth on l-threonine or acetate+glycine. Constitutively synthesized l-serine hydroxymethyltransferase was detected in extracts of Pseudomonas strains D2 and F10. The enzyme could not be detected in strains A1 and N3, probably because of a highly active ;formaldehyde-utilizing' system. 5. Ion-exchange and molecular exclusion chromatography supported other evidence that l-threonine aldolase and allo-l-threonine aldolase activities were catalysed by the same enzyme but that l-serine hydroxymethyltransferase was distinct and different. These results contrast with the specificities of some analogous enzymes of mammalian origin.
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PMID:Bacterial catabolism of threonine. Threonine degradation initiated by L-threonine acetaldehyde-lyase (aldolase) in species of Pseudomonas. 91 18

Serine hydroxymethyltransferase catalyzes the cleavage of a variety of beta-hydroxy-L-amino acids to form glycine and aldehyde products. 4-chloro-L-threonine has been synthesized and shown to be both a substrate and a mechanism-based inactivator of serine hydroxymethyltransferase. kcat values for the formation of glycine in the absence of tetrahydrofolate were determined for 4-chloro-L-threonine and other beta-hydroxyamino acid substrates; an inverse relationship between the rate of cleavage of the amino acid and the electrophilicity of the product aldehyde was demonstrated. 4-Chloro-L-threonine inactivates serine hydroxymethyltransferase in a time- and concentration-dependent manner and exhibits saturation of the rate of inactivation at high concentrations. Our evidence suggests that 4-chlorothreonine undergoes aldol cleavage, and generation of chloroacetaldehyde at the active site of the enzyme results in inactivation. Serine or glycine protect the enzyme against inactivation by chlorothreonine, while tetrahydrofolate does not. The enzyme is also protected from inactivation by 2-mercaptoethanol or by alcohol dehydrogenase and NADH. These studies suggest that halothreonine derivatives that generate electrophilic aldehyde products will be effective inhibitors of serine hydroxymethyltransferase and might be potentially useful chemotherapeutic agents.
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PMID:4-Chlorothreonine is substrate, mechanistic probe, and mechanism-based inactivator of serine hydroxymethyltransferase. 761 18