Defective catabolism of low-density lipoprotein by fibroblasts from patients with I-cell disease.
Skin fibroblast cultures from patients with I-cell disease (mucolipidosis II) are characterized by multiple lysosomal enzyme deficiencies The present studies deal with the consequences of these deficiencies with respect to the metabolism of plasma low-density lipoproteins. Degradation of the protein moiety was defective in I-cells compared with control cells, but the binding and internalization of low density lipoprotein were much less affected. Measurements of low-density lipoprotein degradation in homogenates demonstrated directly for the first time a deficiency of acid proteinase activity in I-cell fibroblasts. Comparison of results in 6-h incubations with those in 24-h incubations showed accumulation of intracellular low-density lipoprotein in I-cell fibroblasts and an accelerating rate of degradation, possibly attributable to intracellular accumulation of low-density lipoprotein substrate. The significance of these findings with respect to low-density lipoprotein metabolism in vivo is discussed.
D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D006938:Hyperlipoproteinemia Type II / Q000378:metabolism; D007223:Infant; D007653:Ketocholesterols / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D009081:Mucolipidoses / Q000378:metabolism*; D011485:Protein Binding; D012867:Skin / Q000378:metabolism*
D007653:Ketocholesterols; D008077:Lipoproteins, LDL; D006903:Hydroxymethylglutaryl CoA Reductases; C003001:7-ketocholesterol