Metabolism of apoA-I as lipid-free protein or as component of discoidal and spherical reconstituted HDLs: studies in wild-type and hepatic lipase transgenic rabbits.
OBJECTIVE
Apolipoprotein (apo)A-I exists in 3 forms in plasma: as lipid-free apoA-I, as a component of pre-beta-migrating discoidal high density lipoproteins (HDLs), and as a component of alpha-migrating spherical HDLs. This study investigates (1) the in vivo metabolism of apoA-I in each of these forms and (2) the effects of hepatic lipase (HL) on apoA-I metabolism.


RESULTS
Wild-type and HL transgenic rabbits were studied. When lipid-free (125)I-apoA-I and 125I-apoA-I in pre-beta-migrating discoidal reconstituted HDLs (rHDLs) were injected into wild-type rabbits, the label rapidly appeared in alpha-migrating particles and decayed with the same fractional catabolic rate (FCR) as when they were injected as a component of spherical rHDLs. Spherical rHDLs did not change in size when they were injected into wild-type rabbits but were reduced in size in HL transgenic rabbits. The FCR of apoA-I in HL transgenic rabbits was double that in wild-type rabbits.


CONCLUSIONS
In vivo, (1) lipid-free apoA-I rapidly incorporates into preexisting alpha-migrating particles, (2) pre-beta-migrating discoidal HDLs are rapidly converted into alpha-migrating HDLs, (3) the FCR of apoA-I is independent of the form in which it is introduced into plasma, and (4) HL reduces the size of alpha-migrating HDLs and increases the rate of catabolism of apoA-I.
Kee
Patrick
P
University Department of Medicine, Royal Adelaide Hospital, Adelaide, Australia.
Rye
Kerry-Anne
KA
Taylor
John L
JL
Barrett
P Hugh R
PH
Barter
Philip J
PJ
D000818:Animals; D030801:Animals, Genetically Modified; D016632:Apolipoprotein A-I / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D008074:Lipoproteins / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000097:blood / Q000737:chemistry* / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D011487:Protein Conformation; D011817:Rabbits; D011994:Recombinant Proteins / Q000097:blood / Q000737:chemistry / Q000378:metabolism
D016632:Apolipoprotein A-I; D007457:Iodine Radioisotopes; D008055:Lipids; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D011994:Recombinant Proteins; C034366:discoidal lipoproteins; D008049:Lipase