CATABOLISM OF CANINE APOLIPOPROTEIN A-L - PURIFICATION, CATABOLIC RATE, ORGANS OF CATABOLISM, AND LIVER SUBCELLULAR CATABOLIC SITE

Abstract

The catabolic site(s) of plasma lipoproteins and apolipoproteins is not established. One of the major apolipoproteins was purified and its catabolic rate and site of catabolism explored. Apolipoprotein (Apo) A-l was purified by column chromatography of canine high-density lipoprotein (HDL) subfraction, HDL3, which was totally delipidated; the purified Apo A-l, MW 28,000, had 1 precipitin line to either anti-Apo A-l, or anti-Apo HDL3 serum. Apo A-l was then iodinated, its catabolic rate measured, and the various organs and the subcellular sites of liver involved in the catabolism were investigated. The T1/2 [half-life] of 125l-Apo A-l in HDL3 was 3.33 .+-. 0.08 days and in plasma 3.52 .+-. 0.17 days. The disappearance curve of radioactivity recovered in density fractions d < 1.110 and d > 1.210 g/ml was the same as that in HDL3, suggesting identical Apo A-l catabolism in each density class. The liver and kidney absorbed more radioactivity than did the spleen, heart, lung and intestine. In subcellular fractions of liver, radioactivity was predominantly recovered in the light mitochondrial fraction. There was a statistically significant correlation between the acid phosphatase relative specific activity and the relative specific radioactivity in each subcellular fraction examined at several time intervals after the injection of 125l-Apo A-l. Direct organelle isolation and demonstration of labeled apolipoprotein uptake indicate that liver lysosomes may play an important role in the catabolism of Apo A-l, as may those of the kidney.