Meta-Biol

• Pathways

In an ATP-dependent reaction, ATP-binding cassette sub-family A member 1 (ABCA1) mediates the movement of intracellular cholesterol (CHOL) to the extracellular face of the plasma membrane. Cholesterol associated with cytosolic vesicles is a substrate for this reaction. Under physiologocal conditions, the active form of ABCA1 is predominantly a tetramer, which is post-translationally modified (palmitoylated and phosphorylated) and is associated with apolipoprotein A-I (APOA1). Defects in ABCA1 can cause Tangier disease (TGD; MIM:205400 aka high density lipoprotein deficiency type 1), an autosomal recessive disorder characterised by significantly reduced levels of plasma high density lipoproteins (HDL) resulting in tissue accumulation of cholesterol esters. Low HDL levels are among the most common biochemical abnormalities observed in coronary heart disease (CHD) patients. Mutations causing TGD include C1417R, Q537R, S1446L, N935S, W590S and R587W (Brooks-Wilson et al. 1999, Lapicka-Bodzioch et al. 2001, Guo et al. 2002, Tanaka et al. 2003).