Submitted to: Mathematical Models Experimental Nutrition Symposium Proceedings
Publication Type: Book / chapter
Publication Acceptance Date: 4/24/2007
Publication Date: 9/20/2007
Citation: Novotny Dura, J., Turnlund, J.R. 2007. Dynamic Modeling of Molybdenum Metabolism in Humans. Virginia: Virginia Polytechnic University. p. 39-50. Interpretive Summary: Molybdenum is an essential mineral for humans. While molybdenum deficiency and toxicity are observed in animals, both are rare in humans, suggesting that humans have mechanisms to regulate the body's exposure to molybdenum under differing dietary conditions. To identify the metabolic pathways by which the body regulates molybdenum, a specialized mathematical technique was used to analyze data from two clinical studies. This technique allowed us to locate two paths which are sensitive to molybdenum exposure. It was found that the body excretes molybdenum more quickly under high molybdenum intakes and more slowly under low molybdenum intakes. In addition, it was found that the body limits molybdenum deposition into body tissues when molybdenum intake is high. Both of these mechanisms work together to prevent both molybdenum deficiency and toxicity in humans. These findings offer a clearer understanding of molybdenum metabolism during depletion and repletion, and will be useful to scientists and health professionals.
Technical Abstract: Molybdenum is an essential nutrient in the human diet and is a cofactor for several enzymes. While intakes can vary widely with geographical region, both deficiency and toxicity in humans are rare. To determine if humans have adaptive mechanisms for maintaining molybdenum status under varying intake levels, two clinical studies were performed. In the first study, healthy males consumed a very low molybdenum diet for 102 days, followed by a high molybdenum diet for 18 days. In the second study, healthy males were administered dietary molybdenum at five different levels consecutively, consuming each intake level for 24 days. In both studies, tracer doses of molybdenum were given orally and intravenously at several time points during the study, and plasma, urine, and fecal samples were analyzed for tracer and tracee molybdenum. Dynamic compartmental modeling of tracer and tracee data was performed using the WinSAAM software package. Modeling results revealed that two physiologic pathways were sensitive to molybdenum exposure: increasing molybdenum intake resulted in (1) increased urinary molybdenum excretion and (2) decreased fraction of molybdenum deposited into tissues. The ability for these pathways to adjust to changes in molybdenum intake may explain why molybdenum deficiency and toxicity in humans is rare.