Decay of hexokinase during reticulocyte maturation: is oxidative damage a signal for destruction?
Proteolysis of hexokinase in cell-free systems prepared from rabbit reticulocytes has been shown previously to be ATP-dependent and apparently mediated by the ubiquitin system (Magnani et al. J. Biol.Chem.261, 8327-8333). We have investigated this phenomenon, but found no substantial loss of hexokinase in cell-free systems prepared from fresh lysates. Storage of lysates at -20 degrees C or addition of a free radical generating system was required to demonstrate rapid ATP-dependent decay. It appears that initial oxidative damage to hexokinase does not abolish its activity but allows it to be recognized by an ATP-dependent proteolytic system. The relevance of this mechanism to in vivo degradation of hexokinase is discussed.
Department of Molecular and Experimental Medicine, Scripps Clinic and Research Foundation, La Jolla, California 92037.
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Thorburn
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Beutler
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology; D002474:Cell-Free System; D003676:Deferoxamine / Q000494:pharmacology; D004905:Erythrocyte Aging; D005609:Free Radicals; D005947:Glucose / Q000494:pharmacology; D005954:Glucosephosphate Dehydrogenase / Q000097:blood; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000097:blood; D006593:Hexokinase / Q000097:blood*; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000097:blood; D010084:Oxidation-Reduction; D011770:Pyruvate Kinase / Q000097:blood; D011817:Rabbits; D012156:Reticulocytes / Q000187:drug effects / Q000201:enzymology*
D005609:Free Radicals; D002248:Carbon Monoxide; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D006593:Hexokinase; D011770:Pyruvate Kinase; D005947:Glucose; D003676:Deferoxamine