Acid inactivation of short-lived rat liver enzymes.
The stabilities of nine rat liver cytosol enzymes were compared at a variety of pH values. The cytosol enzymes studied were (a) those with half-lives in vivo of 3 days or longer: lactate dehydrogenase, arginase, glyceraldehyde phosphate dehydrogenase and alanine aminotransferase, (b) those with half-lives in vivo shorter than 2 days; glucokinase, dihydroorotase, serine dehydratase and tyrosine aminotransferase and (c) catalase, which has an intermediate half-life of 2.5 days for the protein protion. All the enzymes were stable in vitro at neurtal and alkaline pH values. However, at acidic pH values (pH 4): the long-lived enzymes (a) were stable; the short-lived enzymes (b) were completely inactivated with one exception; and catalase was partially inactivated. Tyrosine aminotransferase was the exception in that it is a short-lived enzyme in vivo but  stable under all conditions tested in vitro. The finding that long-lived enzymes are stable in an acid milieu and short-lived enzymes are generally unstable was only observed if certain ligands (NAD+, pyridoxal 5'-phosphate, Mn2+, amino acids) were added to the invitro system. Lysosomal extracts did not accelerate the rate of inactivation of any cytosol enzyme in acidic solutions. These results indicate that if degradation of intracellular enzymes occurs in lysosomes, acid inactivation and denaturation of enzymes may be the initial event in determining the functional half-lives of the enzymes in vivo.
D000135:Acid Phosphatase / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001119:Arginase / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002403:Cathepsins / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D004080:Dihydroorotase / Q000378:metabolism; D004355:Drug Stability; D004789:Enzyme Activation; D005941:Glucokinase / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D012695:L-Serine Dehydratase / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008345:Manganese / Q000494:pharmacology; D051381:Rats; D013347:Subcellular Fractions / Q000201:enzymology; D014444:Tyrosine Transaminase / Q000378:metabolism
D000596:Amino Acids; D008345:Manganese; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D000410:Alanine Transaminase; D014444:Tyrosine Transaminase; D005941:Glucokinase; D000135:Acid Phosphatase; D005966:Glucuronidase; D002403:Cathepsins; D004080:Dihydroorotase; D001119:Arginase; D012695:L-Serine Dehydratase