A sialic acid-specific O-acetylesterase in human erythrocytes: possible identity with esterase D, the genetic marker of retinoblastomas and Wilson disease.
The "nonspecific" esterases are a family of enzymes that were originally identified because of their reaction with synthetic O-acetyl ester substrates. While the electrophoretic polymorphisms of these enzymes have been extremely useful for genetic studies, their biological functions have remained completely unknown. Esterase D is characterized by its reactivity with 4-methylumbelliferyl acetate. This enzyme has recently been of particular interest because of its tight linkage to the putative recessive gene causing retinoblastomas, and to the recessive gene causing Wilson disease. We describe here the partial purification of a human erythrocyte esterase that appears to be highly specific for O-acetylated sialic acids. We next present evidence that suggests that esterase D is identical to this sialic acid-specific O-acetylesterase. First, both activities copurify from human erythrocyte lysates through several different purification steps, each of which use different principles of separation. Second, both activities show a remarkably similar profile of inhibition with a variety of different agents. Third, they both show a nearly identical heat-inactivation profile. This cytosolic sialic acid-specific O-acetylesterase appears to be involved in the "recycling" of O-acetylated sialic acid molecules. Thus, esterase D may be the first nonspecific esterase for which a specific biological role can be predicted.
Varki
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Muchmore
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Diaz
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D000115:Acetylesterase; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors / Q000302:isolation & purification* / Q000378:metabolism; D004789:Enzyme Activation; D004912:Erythrocytes / Q000201:enzymology*; D005134:Eye Neoplasms / Q000201:enzymology; D006527:Hepatolenticular Degeneration / Q000201:enzymology; D006358:Hot Temperature; D006801:Humans; D012175:Retinoblastoma / Q000201:enzymology; D014468:Umbelliferones / Q000378:metabolism
D014468:Umbelliferones; C032078:4-methylumbelliferyl acetate; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; C020118:ESD protein, human; D000115:Acetylesterase; C046298:sialate O-acetylesterase