Phosphate Depletion and Adenine Nucleotide Metabolism in Kidney and Liver

Abstract

Adenosine triphosphate (ATP) and other adenine nucleotides are the major energy coupling mechanism between the energy-producing and the energy-consuming systems in the cells. In a variety of diseased states, an altered metabolism of adenine nucleotides has been implicated in their pathogenesis. There are a few experimental model systems in which one can alter adenine nucleotide metabolism through a different mechanism and study the role of adenine nucleotides in cell functions as shown in Table 1 (1). Although studies using the first three models have been extensively performed, effects of phosphate depletion on the metabolism of adenosine triphosphate and other phosphate compounds in various organ systems have been studied rather to a lesser extent except in red cells, leukocytes, and platelets, where the relationship between a fall in plasma inorganic phosphate (Pi), a fall in tissue Pi, a decrease in tissue ATP, and some forms of cellular dysfunction have been demonstrated (2). Since a major portion of ATP is synthesized from ADP and Pi by oxidative phosphorylation in mitochondria, a deficiency of Pi will result in an impairment of ATP generation. Thus, various organ dysfunctions described in phosphate depletion have been attributed to a fall in the availability of energy-rich phosphate compounds such as ATP. Nevertheless, data on the changes in levels of adenine nucleotides and Pi in different organ systems are limited.