title: In vivo metabolism of apo A-I and apo A-II in subjects with apo A-I(Lys107-->0) associated with reduced HDL cholesterol and Lp(AI w AII) deficiency.
abstract: Apolipoprotein A-I (apo A-I) and apolipoprotein A-II (apo A-II) represent 80 90% of the protein content of high density lipoproteins (HDL). Previously we have identified a Finnish family with an apo A-I variant (Lys107-->0) associated with reduced plasma HDL cholesterol level and decreased lipoprotein (Lp)(AI w AII) concentration compared to unaffected family members. To determine the in vivo metabolism of apo A-I and apo A-II in the carriers of apo A-I (Lys107-->0) variant we radioiodinated normal apo A-I with 125I and apo A-II with 131I and compared the kinetic data of two heterozygous apo A-I(Lysl07-->0) patients (HDL cholesterol leves 0.31 and 0.69 mmol/l) to that of eight normolipidemic, healthy control subjects. Plasma radioactivity curves of 125I-labelled normal apo A-I of the patients demonstrated accelerated clearance of apo A-I compared to control subjects. In the two patients the fractional catabolic rates (FCR) of apo A-I were 0.347/day and 0.213/day, respectively, while the mean FCR of apo A-I of the control subjects was 0.151 +/- 0.041/day. Similarly, the plasma decay curves of the 131I-labelled apo A-II showed more rapid clearance of apo A-II in the two patients than in control subjects. The FCR of apo A-II in the two patients were 0.470/day and 0.234/day, while the mean FCR of apo A-II in control subjects was 0.154 +/- 0.029/day. The calculated production rates of apo A-I were similar in patients and in control subjects, and the production rates of apo A-II were significantly higher in patients than in control subjects. Our results show that the Lp(AI w AII) deficiency in patients with the apo A-I(Lys107-->0) is associated with increased fractional catabolic rates of normal apo A-I and apo A-II, while the production rates of these apolipoproteins are normal (apo A-I) or slightly increased (apo A-II).
authors.affiliation: Department of Medicine, Helsinki University Central Hospital, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Tilly-Kiesi
authors.forename: C J
authors.initials: CJ
authors.lastname: Packard
authors.forename: J
authors.initials: J
authors.lastname: Kahri
authors.forename: C
authors.initials: C
authors.lastname: Ehnholm
authors.forename: J
authors.initials: J
authors.lastname: Shepherd
authors.forename: M R
authors.initials: MR
authors.lastname: Taskinen
mesh_terms: D016632:Apolipoprotein A-I / Q000097:blood* / Q000235:genetics*; D016633:Apolipoprotein A-II / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D004798:Enzymes / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008066:Lipolysis; D017270:Lipoprotein(a) / Q000031:analogs & derivatives* / Q000097:blood / Q000172:deficiency*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D012016:Reference Values
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008076:Cholesterol, HDL; D004798:Enzymes; D008055:Lipids; D017270:Lipoprotein(a); D008074:Lipoproteins; C078260:lipoprotein A-I