Lipoprotein Kinetics and Modeling

Lipoprotein Kinetics and Modeling contains some of the papers presented at a conference on the analysis and modeling of lipoprotein kinetic data held in Phoenix, Arizona. Contributions from both theorists and experimentalists who attended the conference focus on the developments in the use of mathematical modeling in analyzing the lipoprotein kinetics. The conference highlights the role of kinetic modeling in elucidating the dynamic processes involved in lipoprotein metabolism, the result of improper data analysis that can lead to erroneous physiological interpretations, and the emerging complexities in the lipoprotein system.
Organized into six sections comprised of 37 chapters, this book begins with an overview of the theory and applications of kinetic analysis and modeling to lipoproteins. It then discusses the role of kinetic modeling in physiology, the kinetics of apoprotein B in humans, the use of kinetics in investigating the metabolism of very low and intermediate-density lipoproteins, and the models of plasma lipoprotein triglyceride kinetics. It explains the cholesterol kinetics and modeling, the kinetics of high density lipoprotein metabolism in humans, and various techniques for the analysis and modeling of lipoprotein kinetic data such as KABIS (kinetic analysis by interactive simulation) and CONSAM (conversational version of the SAAM modeling program).
This book will be of interest to biologists, physiologists, clinical researchers and experts in computer technology and mathematics.

Contenu

Contributors

Preface

A Tribute

I. Theory

1 Kinetic Analysis and Modeling: Theory and Applications to Lipoproteins

I. Physiological Systems and Models

II. Detailed Mechanistic (Compartmental) Models

III. Special Mathematical Methods

IV. Lipoprotein System

References

2 The Role of Kinetic Modeling in Physiology

Text

References

II. Apoprotein B

3 Apoprotein B Kinetics in Man: Concepts and Questions

I. Experimental Considerations in Modeling ApoB

II. A 1980 Model of ApoB Metabolism

III. The Focus on ApoB in the 1980s

References

4 Very Low Density Lipoprotein Kinetics in Familial Forms of Hypertriglyceridemia

I. Introduction

II. Methods

III. Results

IV. Discussion

References

5 ß-Apolipoprotein Secretion in Man: Investigation by Analysis of 75Se-Labeled Amino Acid Incorporation into Apoprotein

I. Introduction

II. Methods

III. Discussion

Appendix

References

6 The Use of Kinetics in Investigating the Metabolism of Very Low and Intermediate Density Lipoproteins

I. Introduction

II. Classification

III. Methods

IV. Kinetics

V. Discussion

References

7 Deconvolution Analysis of the Conversion of VLDL Apoprotein B to LDL Apoprotein B

I. Subjects

II. Methods

III. Sample Analysis

IV. Calculations

V. Results

VI. Discussion

References

8 Compartmental Models for the Study of Apoprotein B Catabolism in Man

I. Introduction

II. Methods

III. Model Development

IV. Results

V. Discussion

References

9 Heterogeneity of Low Density Lipoproteins: Kinetic Analysis of Asialated Lipoproteins

I. Introduction

II. Methods and Results

III. Discussion

References

10 Molecular and Kinetic Nonidentity of Two Apoprotein B Peptide Classes in Rat Plasma VLDL, IDL, and LDL

I. Introduction

II. Experimental

III. Results and Discussion

IV. Conclusion

References

11 Low Density Lipoprotein Receptor Activity in Man

I. Introduction

II. Preparation and Chemical Modification of Labeled LDL

III. Is Chemically Modified LDL an Appropriate Tracer for the Measurement of Receptor-Independent Catabolism?

IV. Human Turnover Studies

V. Receptor-Mediated LDL Catabolism in Normal and FH Subjects

VI. Effects of Cholestyramine on Receptor-Mediated LDL Catabolism in FH Heterozygotes

References

12 Kinetics of Low Density Lipoproteins Labeled with [14C]Sucrose: Theoretical Basis of a Method for Tracing the Sites of Apoprotein Degradation in Vivo

I. Introduction

II. Theory of Trapped Labels

III. A Practical Problem Associated with Trapped Labels

IV. Results of Computer Simulations [14C]Sucrose-LDL Metabolism

V. Conclusions

References

13 Kinetics of Apolipoprotein B in Normal and Hyperlipidemic Man: Review of Current Data

I. Turnover of VLDL-ApoB

II. Turnover of LDL-ApoB (Apo-LDL)

III. Normal Subjects

IV. Familial Hypercholesterolemia (FH)

V. Familial Combined Hyperlipidemia (FCHL) and Familial Hypertriglyceridemia (FHTG)

VI. Unclassified Hypertriglyceridemia

References

14 What Is ß-VLDL?

I. ß-VLDL of Familial Dysbetalipoproteinemia

II. Kinetic Definition of ß-VLDL

III. Small a2-VLDL and IDL

IV. "Normal" ß-VLDL

V. VLDL "Remnants"

VI. Intermediate Lipoproteins

VII. ß-VLDL of Cholesterol-Fed Animals

VIII. Cellular Metabolism of Intermediate Lipoproteins and ß-VLDL

References

III. Triglycerides

15 Models of Plasma Lipoprotein Triglyceride Kinetics: A Critical Review

I. Radiolabeled Precursors

II. Delipidation Cascade

III. Potential Information in Phospholipid Turnover Data

IV. VLDL Synthesis

V. Importance of Collecting Data for Several Precursors

VI. Slow Components ("Tails") in VLDL-TG Activity

VII. A Slow Production Pathway

VIII. An Alternative to the Slow Production Pathway

References

16 A Model of VLDL Metabolism Based on Its Heterogeneity

I. VLDL-Triglyceride Catabolism in Vivo

II. VLDL-Triglyceride Production

III. Model

References

17 Triglyceride Exchanges and Transfers: Their Role in the Kinetics of Plasma Triglyceride Transport

Text

References

18 Triglyceride Kinetics: Experimental Problems Related to Modeling

Text

References

19 Are Plasma Triglyceride Concentrations Explained by Saturation Kinetics?

I. What Are Saturation Kinetics?

II. What Is the Postulated Role of Saturation Kinetics in the Development of Hypertriglyceridemia?

III. What Is the Evidence for and against Saturation Kinetics as an Explanation for Hypertriglyceridemia?

IV. What Constitutes a Removal Defect for VLDL-TG?

References

20 Studies of Very Low Density Lipoprotein Triglyceride Metabolism in the Pima Indians

I. Summary

II. Introduction

III. Experimental Methods

IV. Results and Discussion

References

21 HDL Triglyceride Kinetics and Exchanges with VLDL in Vivo

I. Introduction

II. Studies

III. Modeling of Exchange between HDL-TG and VLDL-TG

IV. Results

V. Discussion

References

IV. Cholesterol

22 Cholesterol Kinetics and Modeling: Introduction

Text

References

23 A Mathematical Model for Cholesterol Kinetics

I. Model Development

II. Cholesterol Models

III. Model Indeterminacy

IV. Analysis of Data from Precursor Injection

V. Analysis of Specific Activity Data Arising from Injection of Labeled Cholesterol

VI. Analysis of Specific Activity Data Arising from Injection of Labeled Precursor of Cholesterol

VII. Simplified Sampling Schedule

VIII. General Model

IX. Special Problems in Nonlinear Models

References

24 Determination of Total Body Cholesterol: Input-Output Analysis versus Compartmental Analysis

I. General Assumptions

II. Curve Fitting

III. Length of Experiment

IV. Validity of Model

V. Summary

References

25 Cholesterol Disposal in Man: Special Role of HDL Free Cholesterol

I. Backgrou…