On the Existence of a Guanine Nucleotide Trap, the role of Adenosine Kinase and a Possible Cause of Excessive Purine Production in Mammalian Cells

Abstract

It is usually assumed, in part from studies of bacteria, that there is free interconversion of adenosine 5'-monophosphate (AMP) and guanosine 5'-monophosphate (GMP), and that the balance between the 2 nucleotides is maintained exactly by allosteric controls on the activity of the enzymes involved in the interconversion. However, there are good reasons for believing that in most mammalian cells the conversion of GMP to AMP is not an effective process. Furthermore, the activity of certain other enzymes of the purine scavenger pathways will tend to induce imbalance between AMP and GMP. This imbalance will be compensated, but the compensation mechanism will involve increased production and excretion of purines. It is suggested that the operation of this mechanism in the human would result in gout.