Acid phospholipase A1 in liver--a brief survey.
Acid phospholipase A1 activity in liver (rat, human) is predominantly localized in lysosomes. A minor proportion (less than 3% of the total activity) is also present in the Golgi apparatus and the endoplasmic reticulum, presumably due to enzymatically active precursors of the corresponding lysosomal enzyme. Lysosomal phospholipase A1 is the most important enzyme initiating the intralysosomal catabolism of diacylphosphoglycerides. It has been purified 50,600-fold, with a yield of about 26%. The enzyme prefers phosphatidyl-ethanolamine as a substrate, which at 200 microM and pH 4.5, is hydrolysed at a rate of approximately 8.2 U/mg. Lysosomal phospholipase A1 is a glycoprotein of about 29 kDa with an isoelectric point of pH 5.3. Unspecific extralysosomal endogenous inhibitors of this enzyme are pH range, inorganic cations, and various proteins. Divalent cations are more potent inhibitors than monovalent ones. Most endogenous intra- and extracellular proteins inhibit the enzyme, the cationic species exhibiting high inhibitory potencies, glycoproteins only little. Inhibitory proteins act through their binding to the substrate. Lysosomal phospholipase A1 seems to be an important target in drug-induced lipidosis. This lipid storage disease is caused by various cationic amphiphilic drugs that are trapped intralysosomally by protonation. In lysosomes such compounds raise the pH, interact with the polar lipids to be degraded and the lysosomal lipolytic enzymes, such as phospholipase A1. These mechanisms result in impaired intralysosomal phospholipid degradation and hence in intralysosomal phospholipid accumulation.
Kunze
H
H
Max-Planck-Institut für Experimentelle Medizin, Göttingen.
Löffler
B M
BM
D006801:Humans; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054466:Phospholipases A1
D010740:Phospholipases; D010741:Phospholipases A; D054466:Phospholipases A1