Understanding the interrelationship between the synthesis of urea and gluconeogenesis by formulating an overall balanced equation.

It is well known that a strong metabolic interrelationship exists between ureagenesis and gluconeogenesis. In this paper, we present a detailed, overall equation, describing a possible metabolic link between ureagenesis and gluconeogenesis. We adopted a guided approach in which we strongly suggest that students, when faced with the problem of obtaining the overall equation of a metabolic pathway, carefully account for all atoms and charges of the single reactions, as well as the cellular localizations of the substrates, and the related transport systems. If this suggestion is always taken into account, a balanced, overall equation of a metabolic pathway will be obtained, which strongly facilitates the discussion of its physiological role. Unfortunately, textbooks often report unbalanced overall equations of metabolic pathways, including ureagenesis and gluconeogenesis. Most likely the reason is that metabolism and enzymology have been neglected for about three decades, owing to the remarkable advances of molecular biology and molecular genetics. In this paper, we strongly suggest that students, when faced with the problem of obtaining the overall reaction of a metabolic pathway, carefully control if the single reactions are properly balanced for atoms and charges. Following this suggestion, we were able to obtain an overall equation describing the metabolic interrelationship between ureagenesis and gluconeogenesis, in which urea and glucose are the final products. The aim is to better rationalize this topic and to convince students and teachers that metabolism is an important and rewarding chapter of human physiology.