Turnover of synthetic class A amphipathic peptide analogues of exchangeable apolipoproteins in rats. Correlation with physical properties.
Peptide analogues of the class A amphipathic helixes from exchangeable apolipoproteins mimic apolipoprotein (apo) A-I in a number of ways, including the ability to activate the enzyme lecithin:cholesterol acyltransferase, to associate with high density lipoproteins (HDLs), and to form HDL-like particles in the presence of lipids. This study investigated the metabolic properties of several of these peptide analogues in the rat. Peptide analogues studied were 18A (referred to as L-18A to differentiate it from D-18A, and which mimics apolipoprotein amphipathic helical domains in its charge distribution), 37pA (a dimer of two 18A monomers separated by a proline), 18R (with reversed charge distribution compared with 18A), and D-18A (identical in amino acid sequence to 18A but synthesized from D-amino acids). Peptides were radiolabeled with 125I. In addition, metabolism of rat and human 125I-apo A-I and human 14C-apo A-I was studied; no significant differences in clearance of these preparations were seen. Clearance data were fitted to multiexponential equations to give half-times of clearance; biexponential equations consistently provided the best nonlinear least-squares curve fit. The order of relative lipid affinity determined in vitro was 37pA greater than apo A-I greater than D-18A = L-18A greater than 18R. Half-times of clearance were in the same approximate rank order: 37pA, 6.9 +/- 3.3 hours (mean +/- SD); apo A-I, 6.9 +/- 1.8 hours; D-18A, 4.0 +/- 1.0 hours; L-18A, 4.6 +/- 1.6 hours; and 18R, 0.9 +/- 0.1 hour.(ABSTRACT TRUNCATED AT 250 WORDS)
Garber
D W
DW
Atherosclerosis Research Unit, University of Alabama, Birmingham.
Venkatachalapathi
Y V
YV
Gupta
K B
KB
Ibdah
J
J
Phillips
M C
MC
Hazelrig
J B
JB
Segrest
J P
JP
Anantharamaiah
G M
GM
D000327:Adsorption; D000818:Animals; D016632:Apolipoprotein A-I / Q000493:pharmacokinetics*; D002942:Circular Dichroism; D006801:Humans; D008297:Male; D010455:Peptides / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D016632:Apolipoprotein A-I; D010455:Peptides