Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.2.13 (aldolase)
 3,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven cytosolic enzymes with varying half-lives (ornithine decarboxylase, 0.9 h; tyrosine aminotransferase, 3.1 h; tryptophan oxygenase, 3.3 h; serine dehydratase, 10.3 h; glucokinase, 12.7 h; lactate dehydrogenase, 17.0 h; aldolase, 17.4 h) were found to be autophagically sequestered at the same rate (3.5%/h) in isolated rat hepatocytes. Autophagy was measured as the accumulation of enzyme activity in the sedimentable organelles (mostly lysosomes) of electrodisrupted cells in the presence of the proteinase inhibitor leupeptin. Inhibitors of lysosomal fusion processes (vinblastine and asparagine) allowed accumulation of catalytically active enzyme (in prelysosomal vacuoles) even in the absence of proteolytic inhibition, showing that no inactivation step took place before lysosomal proteolysis. The completeness of protection by leupeptin indicates, furthermore, that a lysosomal cysteine proteinase is obligatorily required for the initial proteolytic attack upon autophagocytosed proteins. The experiments suggest that sequestration and degradation of normal cytosolic proteins by the autophagic-lysosomal pathway is a nonselective bulk process, and that nonautophagic mechanisms must be invoked to account for differential enzyme turnover.
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PMID:Nonselective autophagy of cytosolic enzymes by isolated rat hepatocytes. 239 70

Vitamin B(6)-dependent enzymes may be grouped into five evolutionarily unrelated families, each having a different fold. Within fold type I enzymes, L-threonine aldolase (L-TA) and fungal alanine racemase (AlaRac) belong to a subgroup of structurally and mechanistically closely related proteins, which specialised during evolution to perform different functions. In a previous study, a comparison of the catalytic properties and active site structures of these enzymes suggested that they have a catalytic apparatus with the same basic features. Recently, recombinant D-threonine aldolases (D-TAs) from two bacterial organisms have been characterised, their predicted amino acid sequences showing no significant similarities to any of the known B(6) enzymes. In the present work, a comparative structural analysis suggests that D-TA has an alpha/beta barrel fold and therefore is a fold type III B(6) enzyme, as eukaryotic ornithine decarboxylase (ODC) and bacterial AlaRac. The presence of both TA and AlaRac in two distinct evolutionary unrelated families represents a novel and interesting example of convergent evolution. The independent emergence of the same catalytic properties in families characterised by completely different folds may have not been determined by chance, but by the similar structural features required to catalyse pyridoxal phosphate-dependent aldolase and racemase reactions.
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PMID:Threonine aldolase and alanine racemase: novel examples of convergent evolution in the superfamily of vitamin B6-dependent enzymes. 1268 35