In the experiment shown below, fibroblasts obtained from a normal subject (closed symbols) or from a patient homozygous for familial hypercholester-olemia (FH Homozygote) (open symbols) were grown in monolayer cultures. At time zero, the medium was replaced with fresh medium depleted of lipoproteins, and HMG-CoA reductase activity was measured in extracts prepared at the indicated times (panel a). Twenty-four hours after addition of the lipoprotein-deficient medium, human LDL was added to the cells at the indicated levels, and HMG-CoA reductase activity was measured at the indicated time.

Based on your understanding of HMG-CoA reductase regulation, explain the following results:
(a) When cultured in the presence of LDL, normal cells showed low activity of HMG-CoA reductase. After removal of lipopoteins, including LDL, HMG-CoA reductase activities increased some 50- to 100-fold in normal cells (panel a). This high level of enzyme activity was rapidly suppressed upon addition of LDL back to normal cells (panel b).
(b) Cells from FH individuals showed high levels of reductase activity, whether cultured in the presence or absence of LDL.

Transcribed Image Text:

AFT ER REMOVAL OFLIPOPAOTEINS AFTER ADDITION OF LDL 200 FH Homozygote 2 LDL 100 None Normal 2 ㎍/ml E 20 2 20 ㎍/ml 0 16 24 32 Hours 4 8 Hours 8