RAPID IN-VIVO TRANSPORT AND CATABOLISM OF HUMAN APOLIPOPROTEIN A-VI-1AND SLOWER CATABOLISM OF THE APOA-IV-2 ISOPROTEIN

Apolipoprotein (apo) A-IV is a polymorphic, intestinally derived apoli poprotein that is genetically linked to and similar in structure to ap oA-I, the major apolipoprotein in high density lipoproteins (HDL). Apo A-IV plays a potentially important role in lipoprotein metabolism and reverse cholesterol transport, but its in vivo metabolism is poorly un derstood. In order to gain insight into factors modulating apoA-IV met abolism in humans, the in vivo kinetics of the two major human apoA-IV isoproteins apoA-IV-1 and apoA-IV-2 were investigated in normolipidem ic human subjects. I-131-apoA-IV-1 and I-125-apoA-IV-2 were reassociat ed with autologous plasma and injected into study subjects. Analysis o f the kinetic data revealed a rapid mean fractional catabolic rate (FC R) for apoA-IV-1 of 2.42 +/- 0.11 d-1. The mean production, or transpo rt, rate of apoA-IV-1 was 16.3 +/- 1.4 mg/kg per d. Plasma apoA-IV con centrations were highly correlated with apoA-IV production rate (r = 0 .84, P < 0.001) and not correlated with apoA-IV fractional catabolic r ate (r = 0.25, P = NS). The mean FCR of apoA-IV-2 was 2.21 +/- 0.10 d- 1. In the ten subjects in whom I-131-apoA-IV-1 and I-125-apoA-IV-2 wer e simultaneously injected, the FCR of apoA-IV-2 was significantly slow er by paired t test (P = 0.003). The FCR of apoA-IV-2 in an apoA-IV-2/ 2 homozygote was only 1.49 d-1, substantially slower than in all other subjects. We conclude that: (a) apoA-IV is a rapidly catabolized apol ipoprotein in humans, with a fractional catabolic rate more than 10 ti mes greater than that of apoA-1; (b) apoA-IV has a high absolute trans port rate similar to that of apoA-1; (c) plasma levels of apoA-IV are primarily determined by apoA-IV production rate in normolipidemic subj ects; and (d) the fractional catabolic rate of the common variant apoA -IV-2 is slower than that of the wild-type apoA-IV-1.