Meta-Biol

• Pathways

The assembly of very low-density lipoprotein (VLDL) occurs in two steps (Olofsson et al. 2000). In the first step, apolipoprotein B-100 (APOB(28-4563), APOB-100) is co- and post-translationally lipidated by MTP (microsomal triacylglycerol transfer protein) in the form of a MTP:PDI (protein disulfide isomerase) heterodimer (Gordon et al. 1995), forming a pre-VLDL. This occurs in the rough endoplasmic reticulum (RER) lumen. The pre-VLDL is loosely associated with the RER membrane. MTP in vitro binds small amounts of PL and TAG (annotated here as one molecule of each) and efficiently transfers the bound lipid between membranes (Atzel & Wetterau 1994). In vivo, MTP:PDI directly interacts with APOB-100 polypeptide (Wu et al. 1996), and is thought to transfer lipid from the endoplasmic reticulum membrane to nascent APOB-100. In humans, APOB-100 is expressed in the liver and forms VLDL whereas APOB-48 is expressed in the intestine and forms chylomicrons.