Journal of Lipid Research, Vol 31, 1031-1042, Copyright © 1990 by Lipid Research, Inc.

ARTICLES

Nonuniform radiolabeling of VLDL apolipoprotein B: implications for the analysis of studies of the kinetics of the metabolism of lipoproteins containing apolipoprotein B

R Ramakrishnan, Y Arad, S Wong and HN Ginsberg
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032.

Radiolabeling of whole lipoproteins or individual apolipoproteins has been an essential tool for the determination of the kinetics of apolipoprotein metabolism in vivo. Mathematical analysis of specific radioactivity (SA) or total radioactivity data has demonstrated the existence of significant complexity in the plasma decay curves of several apolipoproteins. Results obtained during development of methods to study the metabolism of apolipoprotein B (apoB) in very low density lipoprotein (VLDL) subclasses isolated according to flotation (Sf) rates from whole radiolabeled (d less than 1.006 g/ml) VLDL suggested nonuniform radiolabeling of apoB in the three Sf subclasses being studied. We therefore determined apoB SA in VLDL Sf subclasses in ten hypertriglyceridemic and five normal subjects. After radioiodination of apoB in whole VLDL, different apoB SA were found in Sf 400-100, Sf 100- 60, and Sf 60-20. The pattern of labeling was quite variable among subjects. On average, apoB SA in the VLDL tracer was greatest in Sf 400- 100, and least in Sf 60-20. Nonuniform labeling could also be demonstrated in five studies in which samples were obtained 3 min after intravenous injection of the tracer into subjects with a wide range of plasma triglycerides. Nonuniform labeling of apoB in whole VLDL was also demonstrated in two of the subjects by isolating subclasses of their VLDL that did not bind to an anti-apolipoprotein E immunoaffinity column. These results indicate that the usual assumption of homogeneous labeling of apoB may be erroneous. We have derived a simple mathematical formula to study the consequences of this assumption in estimating kinetic parameters. It is shown that an erroneous assumption of homogeneous tracer labeling may significantly underestimate or overestimate the true production rate, even in a simple two-pool model. Identification of labeling characteristics and incorporation of this information into the mathematical analysis of the plasma radioactivity data can improve the accuracy of the analysis as well as the sensitivity of compartmental models generated by such data.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Rashid, B. W. Patterson, and G. F. Lewis Thematic review series: Patient-Oriented Research. What have we learned about HDL metabolism from kinetics studies in humans? J. Lipid Res., August 1, 2006; 47(8): 1631 - 1642. [Abstract] [Full Text] [PDF]

				P. H. R. Barrett, D. C. Chan, and G. F. Watts Thematic review series: Patient-Oriented Research. Design and analysis of lipoprotein tracer kinetics studies in humans J. Lipid Res., August 1, 2006; 47(8): 1607 - 1619. [Abstract] [Full Text] [PDF]

				K. Conde-Knape, K. Okada, R. Ramakrishnan, and N. S. Shachter Overexpression of apoC-III produces lesser hypertriglyceridemia in apoB-48-only gene-targeted mice than in apoB-100-only mice J. Lipid Res., December 1, 2004; 45(12): 2235 - 2244. [Abstract] [Full Text] [PDF]

				K. Conde-Knape, A. Bensadoun, J. H. Sobel, J. S. Cohn, and N. S. Shachter Overexpression of apoC-I in apoE-null mice: severe hypertriglyceridemia due to inhibition of hepatic lipase J. Lipid Res., December 1, 2002; 43(12): 2136 - 2145. [Abstract] [Full Text] [PDF]

				F. Pont, L. Duvillard, B. Verges, and P. Gambert Development of Compartmental Models in Stable-Isotope Experiments : Application to Lipid Metabolism Arterioscler. Thromb. Vasc. Biol., June 1, 1998; 18(6): 853 - 860. [Abstract] [Full Text] [PDF]

				H. Zulewski, R. Ninnis, A. R. Miserez, M. W. Baumstark, and U. Keller VLDL and IDL apolipoprotein B-100 kinetics in familial hypercholesterolemia due to impaired LDL receptor function or to defective apolipoprotein B-100 J. Lipid Res., February 1, 1998; 39(2): 380 - 387. [Abstract] [Full Text]