Human proapoA-ITangier: isolation of proapoA-ITangier and amino acid sequence of the propeptide.

The metabolic defect in Tangier disease is an increased catabolism of apoA-ITangier. The plasma concentration of proapoA-ITangier (apoA-I1 isoform) is increased in patients with Tangier disease. ProapoA-ITangier has been purified to homogeneity, and the amino acid sequence of the propeptide determined by automated Edman degradation. The propeptide sequence was Arg-His-Phe-Trp-Gln-Gln which is identical to the propeptide sequence of normal proapoA-I. These studies indicate that the increase in plasma proapoA-ITangier is not due to a structural defect in the propeptide sequence of proapoA-ITangier and a defect in conversion of proapoA-ITangier to mature apoA-ITangier. The increased catabolism of apoA-ITangier is due to a primary structural defect in mature apoA-ITangier.