Abstract
The activity of HMG CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis, is repressed by serum in normal fibroblasts. We measured HMG CoA reductase by the conversion of [3-14C] HMG CoA to mevalonate in confluent fibroblast cultures incubated for 24 hr in Eagle's MEM with and without 10% fetal calf serum (FCS). Five normals (NLS) and 4 patients with HHLPII were studied (TP, JaP, LH, LC: Levy et al., Ann. Int. Med. 77:267, 1972). HMG CoA reductase in NLS was 1.10 ± 0.53 (avg ± SD) units (pmol/min/mg protein) with FCS and 7.70 ± 3.78 units without FCS. HMG CoA reductase in HHLPII cells was 7.83 j± 3.69 units with FCS and 10.97 ± 4.80 units without FCS. Ratios of HMG CoA reductase activity with/without FCS equals 0.16 ± 0.07 in NL cells and 0.68 ± 0.31 in all 4 HHLPII cell lines (p 0.005). An intermediate value, 0.34 ± 0.09, was observed in one HHLPII cell line (LH) which differed significantly from the other 3 HHLPII values, 0.80 ± 0.26 (p 0.05), and from NL values (p 0.01). Conclusions: (1) HMG CoA reductase levels were not inhibited by serum in cells from 3 patients with HHLPII, which confirms and extends to new patients the observation of Goldstein et al. (PNAS 70:2804, 1973). (2) Genotypic variation is suggested by one patient, LH, a phenotypic HHLPII, who exhibited partial inhibition by FCS.
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Breslow, J., Lux, S., Spaulding, D. et al. 3-HYDROXY-3 METHYL GLUTARYL COENZYME A (HMG COA) REDUCTASE ACTIVITY IN FIBROBLASTS FROM PHENOTYPIC HOMOZYGOUS TYPE II HY-PERLIPOPROTEINEMIA (HHLPII). Pediatr Res 8, 387 (1974). https://doi.org/10.1203/00006450-197404000-00284
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DOI: https://doi.org/10.1203/00006450-197404000-00284