Extracellular metabolism of nucleotides in the nervous system

1. A variety of surface-located enzymes are involved in the metabolism of extracellular nucleotides. The biochemical properties of some of these are briefly discussed. 2. The molecular identity of ecto-diadenosine polyphosphate hydrolase has not yet been revealed. On neural cells the enzyme catalyses the hydrolysis of ApnA to Apn-1 and AMP. 3. The molecular structure of ATP-diphosphohydrolase has recently been identified. The enzyme occurs in essentially all tissues where it catalyses the extracellular hydrolysis of ATP and ADP with the formation of AMP. 4. Ecto-5'-nucleotidase is a GPI-anchored glycoprotein and catalyses the formation of AMP to adenosine. In the adult brain, and as revealed by immunocytochemistry, the enzyme is mainly associated with astrocytes. It is associated with developing nerve cells and cultured neural cells. In vitro its inhibition or suppression of its synthesis result in the inhibition of neurite formation and long-time survival of neural cells. Continued extracellular hydrolysis of AMP and formation of adenosine thus appear to be essential for neural differentiation and survival.