FIGURE 1.

Possible mechanism for increased synthesis of cIMP by sGC in response to hypoxia. The intracellular ITP is primarily derived from the deamination of ATP, which is the most abundant nucleotide inside the cell. Under normal conditions, ITP is mostly converted to IMP by ITPA and the cytosolic level of ITP is negligible. Under hypoxia, ATP deamination is stimulated and/or ITPA is inhibited. This leads to elevated ITP level, increased formation of cIMP by sGC, and hence enhanced cIMP action. Cyclic IMP is degraded by phosphodiesterase (PDE). Full arrows indicate activation and dotted arrows indicate inhibition. IMP, inosine 5′-monophosphate; ITPA, inosine triphosphatase.