HYPERCATABOLISM OF LIPOPROTEIN-FREE APOLIPOPROTEIN-A-I IN HDL-DEFICIENT MUTANT CHICKENS

The Wisconsin Hypoalpha Mutant (WHAM) chicken has a sex-linked mutatio n associated with a 90% reduction in high-density lipoprotein (HDL) ch olesterol and apolipoprotein A-I (apoA-I). In the present studies, we did not detect a defect in apoA-I synthesis or secretion in liver or i ntestine. We tested the hypothesis that apoA-I is not binding properly to lipoprotein particles and is undergoing hypercatabolism. We theref ore studied the in vivo turnover of lipid-free I-125-apoA-I. Its turno ver was fourfold faster in WHAM chickens than in normal chickens. The I-125-apoA-I equilibrated more slowly with HDL in the WHAM chickens, a nd these animals had a much larger steady-state pool of lipid-free apo A-I than did control chickens. To determine the tissue sites of degrad ation of apoA-I, the tissue distribution of I-125-tyramine cellobiose apoA-I was assessed. The liver and kidneys were the major sites of apo A-I degradation, but in the WHAM chickens, the kidney made a twofold l arger contribution to apoA-I degradation than in normal chickens. Tota l plasma phospholipid levels are reduced by 44% to 78% in the WHAM chi ckens. A phospholipid deficit might explain the elevated lipid-free ap oA-I pool and, secondarily, the HDL deficiency of the WHAM chickens.