Use of model-based compartmental analysis to study vitamin A kinetics and metabolism.
We discuss the use of mathematical modeling, and specifically model-based compartmental analysis, to analyze vitamin A kinetic data obtained in rat and human studies over the past 25 years. Following an overview of whole-body vitamin A metabolism, a review of early kinetic studies, and an introduction to the approach and terminology of compartmental analysis, we summarize studies done in this laboratory to develop models of whole-body vitamin A metabolism in rats at varying levels of vitamin A status. Highlights of the results of these studies include the extensive recycling of vitamin A among plasma and tissues before irreversible utilization and the existence of significant extrahepatic pools of the vitamin. Our studies also document important differences in vitamin A kinetics as a function of vitamin A status and the importance of plasma retinol pool size in vitamin A utilization rate. Later we describe vitamin A kinetics and models developed for specific organs including the liver, eyes, kidneys, small intestine, lungs, testes, adrenals, and remaining carcass, and we discuss the effects of various exogenous factors (e.g., 4-HPR, dioxin, iron deficiency, dietary retinoic acid, and inflammation) on vitamin A dynamics. We also briefly review the retrospective application of model-based compartmental analysis to human vitamin A kinetic data. Overall, we conclude that the application of model-based compartmental analysis to vitamin A kinetic data provides unique insights into both quantitative and descriptive aspects of vitamin A metabolism and homeostasis in the intact animal.
Cifelli
Christopher J
CJ
Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania 16801, USA.
Green
Joanne Balmer
JB
Green
Michael H
MH
D000818:Animals; D001825:Body Fluid Compartments / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D015233:Models, Statistical; D009928:Organ Specificity / Q000502:physiology; D051381:Rats; D014801:Vitamin A / Q000378:metabolism* / Q000493:pharmacokinetics
D014801:Vitamin A