The seventh myth of lipoprotein(a): where and how is it assembled?

Our understanding of the genetics, metabolism and pathophysiology of the at herogenic plasma lipoprotein Lp(a) has considerably increased over past yea rs. Nevertheless, the precise mechanisms regulating the biosynthesis and as sembly of Lp(a) are poorly understood and controversially discussed. Lp(a) plasma concentrations are determined by synthesis and not by degradation. T ranscriptional and post-translational mechanisms have been identified as re gulating Lp(a) production in primary hepatocytes and transfected cell lines . Assembly of Lp(a) occurs extracellularly from newly synthesized apolipopr otein(a) and circulating LDL. This view has recently been challenged by in- vivo kinetic studies in humans which are compatible with an intracellular a ssembly event. Lp(a) assembly is a complex two-step process of multiple non -covalent interactions between apolipoprotein(a) and apolipoprotein B-100 o f LDL followed by covalent disulfide linkage of two free cysteine residues on both proteins. Curr Opin Lipidol 10:275-283. (C) 1999 Lippincott William s & Wilkins.