Journal of Lipid Research, Vol 38, 1535-1543, Copyright © 1997 by Lipid Research, Inc.

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Production of apolipoprotein B-67 in apolipoprotein B-67/B-100 heterozygotes: technical problems associated with leucine contamination in stable isotope studies

FK Welty, AH Lichtenstein, PH Barrett, GG Dolnikowski, JM Ordovas and EJ Schaefer
Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, New England Medical Center, Boston, MA 02111, USA.

In vivo kinetics of apoB were performed in three apoB-67/apoB-100 heterozygotes using a primed-constant infusion of (5,5,5-(2)H3)- leucine. Mean plasma VLDL and LDL apoB-67 concentrations were 0.05 +/- 0.01 mg/dl and 0.62 +/- 0.17 mg/dl, respectively, which were 0.2% and 2.8% of total plasma apoB concentrations. When cation exchange chromatography was used to separate plasma amino acids from fragments of polyacrylamide gels, the tracer/tracee ratio at plateau for VLDL apoB-67 was less than 50% of that observed when centrifugation was used. Mean fractional catabolic rate for LDL apoB-67 was 2-fold higher when the lower plateau was used in multicompartmental analysis compared to the higher plateau (0.70 +/- 0.21 versus 0.37 +/- 0.06 pools per day, P = 0.06). The lower plateau resulted from introduction of unlabeled leucine during cation exchange chromatography; therefore, all samples were processed with centrifugation. Mean fractional catabolic rates for VLDL and LDL apoB-67 were not significantly different from VLDL and LDL apoB-100 (VLDL: 9.7 +/- 3.4 versus 18.1 +/- 8.6 pools per day, respectively, P = 0.19; LDL: 0.37 +/- 0.06 versus 0.34 +/- 0.11 pools per day, respectively, P = 0.66). Mean secretion rate of VLDL apoB-67 was 5.6% of VLDL apoB-100 (0.20 +/- 0.04 versus 3.6 +/- 1.3 mg/kg/day, P = 0.01). Fifty-three % of apoB-67 was directly removed from VLDL compared to only 3.5% of apoB-100 (P = 0.003), thus accounting for the lower proportion of apoB-67 in LDL (3.3 +/- 1.8%) as compared to VLDL (11.2 +/- 2.5%). Mean LDL production rate for apoB-67 was 2.6% of LDL apoB-100 (0.09 +/- 0.02 versus 3.50 +/- 1.39 mg/kg/day, P = 0.05). Thus, decreased secretion of apoB-67 is responsible for low levels of apoB-67.
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