Modification of VLDL apoprotein B by acetaldehyde alters apoprotein B metabolism

Abstract

Acetaldehyde (AcA), the first metabolite in ethanol oxidation, is chemically highly reactive and forms adducts with proteins in alcoholics. We examined the effect of very low density lipoprotein (VLDL) apoprotein B (apoB) modification by AcA on the metabolism of apoB-containing lipoproteins [VLDL, intermediate density lipoprotein (IDL) and low density lipoprotein (LDL)]. VLDL-B was selectively radiolabelled with either 125I or 131I and modified with various AcA concentrations, and the preparation was injected into rabbits simultaneously with control-treated VLDL. AcA modification of VLDL-B reduced the fractional catabolic rates for VLDL-B, IDL-B, and LDL-B. The direct removal of VLDL-B from plasma was decreased, whereas the fraction of VLDL-B converted to IDL-B was increased. The effect of AcA modification on the overall fraction of VLDL converted to LDL was qualitatively heterogeneous: VLDL-B modification with 2.0 mM AcA reduced the fraction converted, whereas modification with 4.0 and 8.0 mM AcA increased it. The concentrations of AcA used were higher than those reported in blood after ethanol ingestion, but the experiments serve to test in qualitative terms the model of VLDL-B modification by AcA. The observed VLDL-B alteration by AcA in vivo in alcoholics is most likely to be close to the minor modification used here, thereby theoretically contributing to the low IDL and LDL levels observed in alcoholics.