In vivo interaction of synthetic acylated apopeptides with high density lipoproteins in rat.
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.
Ponsin
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Sparrow
J T
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Gotto
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Pownall
H J
HJ
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
D016632:Apolipoprotein A-I; D001054:Apolipoproteins A; D003902:Detergents; D036341:Intercellular Signaling Peptides and Proteins; D008075:Lipoproteins, HDL; D010455:Peptides; C043948:lipid-associating peptides