title: In vivo interaction of synthetic acylated apopeptides with high density lipoproteins in rat.
abstract: The metabolism of synthetic peptide analogues of high density lipoprotein (HDL) apoproteins has been studied in the rat. These compounds are 15-amino acid lipid associating peptides (LAPs) bearing acyl chains of various lengths (0-16 carbon units). After injection of each 125I-LAP, the serum decay curves suggested a two-compartment process with a clearance rate decreasing when the acyl chain lengths increased. The similarity between the apparent half-life of C16-LAP and that of apoprotein A-I as well as the chromatographic analysis of rat serum were consistent with a partitioning of the LAPs between HDL and the aqueous phase. This was strongly dependent upon the acyl chain length of the LAPs. The distribution volumes of the 125I-LAPs in organs were measured 10 min after injection. The results were analyzed using a model explicitly predicting the organ distribution volumes of HDL and the equilibrium constant (Keq) of the binding of each LAP to HDL. HDL distributed significantly in the adrenals (250 microliters/g), liver (80 microliters/g), and ovaries (55 microliters/g), but not in the kidneys. This suggests that the binding of HDL apoproteins to kidneys, reported by others, was due to the uptake of free apoproteins. The Keqs exhibited a log-linear relationship with respect to the acyl chain length of the LAPs. Each carbon unit added to the acyl chain decreased the free energy of association by a constant value (0.3 kcal mol-1). This clearly showed a strict hydrophobic effect similar to that previously observed in vitro.
authors.forename: G
authors.initials: G
authors.lastname: Ponsin
authors.forename: J T
authors.initials: JT
authors.lastname: Sparrow
authors.forename: A M
authors.initials: AM
authors.lastname: Gotto
authors.forename: H J
authors.initials: HJ
authors.lastname: Pownall
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I; D001054:Apolipoproteins A / Q000097:blood; D055598:Chemical Phenomena; D002621:Chemistry; D003902:Detergents; D005260:Female; D006207:Half-Life; D036341:Intercellular Signaling Peptides and Proteins; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D010455:Peptides / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D003902:Detergents; D036341:Intercellular Signaling Peptides and Proteins; D008075:Lipoproteins, HDL; D010455:Peptides; C043948:lipid-associating peptides