Abstract
Tangier disease is an autosomal recessive disorder characterized by absence of normal high density lipoproteins (HDL), storage of cholesterol esters in foamcells, and neuropathy, Small amounts of an abnormal HDL (HDLT) having only partial immunochemical identity with normal HSL occur in Tangier plasma, HDL has recently been shown to contain two major protein subunits, one with C-terminal threonine (R-Thr), the other with C-terminal glutaminc (R-Gln). R-Thr and R-Gln are immunochemically different and occur in normal HDL, in a ratio of 2–4:1 (R-Thr:R-Gln). We now report investigations of these two moieties in HDLT isolated from a Tangier homozygote.
R-Gln was identified in delipidated HDLx (apo HDLT) by polyacrylamide gel electrophoresis (PGE), DEAE cellulose chromatography and immunodiffusion with antisera to R-Gln and normal HDL (anti-HDL). An antiserum to HDLT (antiHDLT) reacted withR-Gln and absorption of antiHDL with apoHDLT removed all reactivity to R-Gln, confirming the presence of R-Gln in HDLT. R-Gln from apoHDLT was electrophoretically and immunochemically identical with normal R-Gln. At protein concentrations at which R-Gln was readily apparent, PGE, DEAE cellulose chromatography and immunodiffusion demonstrated R-Thr in apoHDL but not in apoHDLT. However, antiHDLT reacted weakly with R-Thr suggesting the presence of traces of R-Thr in apoHDLT. Using antiR-Thr sera and increasing the amount of apo-HDLT 10 to 100-fold, an antigen was seen that migrated on PGE and eluted from DEAE the same as normal R-Thr and was immunochemically dentical with R-Thr.
These results indicate a markedly disproportionate decrease in R-Thr compared to R-Gln in Tangier disease and suggest the hereditary defect is one of control of R-Thr synthesis.
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Lux, S., Levy, R., Gotto, A. et al. Studies of the Protein Defect in Tangier Disease. Pediatr Res 4, 439–440 (1970). https://doi.org/10.1203/00006450-197009000-00025
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DOI: https://doi.org/10.1203/00006450-197009000-00025