title: Hypercatabolism of lipoprotein-free apolipoprotein A-I in HDL-deficient mutant chickens.
abstract: The Wisconsin Hypoalpha Mutant (WHAM) chicken has a sex-linked mutation associated with a 90% reduction in high-density lipoprotein (HDL) cholesterol 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 intestine. We tested the hypothesis that apoA-I is not binding properly to lipoprotein particles and is undergoing hypercatabolism. We therefore studied the in vivo turnover of lipid-free 125I-apoA-I. Its turnover was fourfold faster in WHAM chickens than in normal chickens. The 125I-apoA-I equilibrated more slowly with HDL in the WHAM chickens, and these animals had a much larger steady-state pool of lipid-free apoA-I than did control chickens. To determine the tissue sites of degradation of apoA- I, the tissue distribution of 125I-tyramine cellobiose apoA-I was assessed. The liver and kidneys were the major sites of apoA-I degradation, but in the WHAM chickens, the kidney made a twofold larger contribution to apoA-I degradation than in normal chickens. Total plasma phospholipid levels are reduced by 44% to 78% in the WHAM chickens. A phospholipid deficit might explain the elevated lipid-free apoA-I pool and, secondarily, the HDL deficiency of the WHAM chickens.
authors.affiliation: Department of Biochemistry, University of Wisconsin-Madison 53706-1569.
authors.forename: S A
authors.initials: SA
authors.lastname: Schreyer
authors.forename: L K
authors.initials: LK
authors.lastname: Hart
authors.forename: A D
authors.initials: AD
authors.lastname: Attie
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis* / Q000235:genetics; D002645:Chickens; D008076:Cholesterol, HDL / Q000172:deficiency*; D005260:Female; D008040:Genetic Linkage; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D010743:Phospholipids / Q000097:blood; D012333:RNA, Messenger / Q000096:biosynthesis; D014439:Tyramine
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D010743:Phospholipids; D012333:RNA, Messenger; D014439:Tyramine