In vivo catabolism of human low density lipoprotein in the rat is mediated by a nonsaturable, low-affinity mechanism.
The degradation of human low density lipoprotein (LDL) was analyzed in fasted rats treated for 3 days with either 4-aminopyrazolo-(3,4-d)pyrimidine (4APP) or saline. Treatment with 4APP caused an 80% decrease in serum cholesterol concentration. The mono-exponential serum decay of a tracer amount of labelled LDL was changed neither by 4APP treatment, nor by the simultaneous injection of a bolus of unlabelled LDL. The sites of degradation of human LDL were determined using the nondegradable labelling compound O-(4-diazo-3-[125I]iodobenzoyl)sucrose (D125IBS). The sites of degradation and the rate of degradation of D125IBS labelled LDL were also not affected by 4APP treatment or by injection of a bolus of unlabelled LDL. It is concluded that human LDL is catabolised in the rat by way of a nonsaturable, low-affinity mechanism.
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002784:Cholesterol / Q000097:blood; D005215:Fasting; D006207:Half-Life; D006801:Humans; D007457:Iodine Radioisotopes; D007463:Iodobenzoates / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000187:drug effects / Q000378:metabolism
D007457:Iodine Radioisotopes; D007463:Iodobenzoates; D008077:Lipoproteins, LDL; C004420:4-aminopyrazolo(3,4-d)pyrimidine; C044133:O-(4-diazo-3-iodobenzoyl)sucrose; D002784:Cholesterol; D000225:Adenine