Avibactam sodium (NXL-104)

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

PDE4A PDE4B PDE4C and PDE4D are phosphodiesterases which play a role in breaking down cyclic adenosine monophosphate (cAMP) into the nucleotide form. These enzymes are also referred to as cAMP-specific phosphodiesterases. Mechanically they hydrolyze cAMP by converting it into AMP therefore regulating its cellular level. The molecular mass of these enzymes varies but all are within the range of 68 to 134 kDa. PDE4 enzymes are found in various tissues including the brain lungs and immune cells with distinct expression patterns for each subtype.

Biological function summary

These enzymes modulate intracellular concentrations of cAMP a significant secondary messenger involved in signal transduction. PDE4 proteins are not part of a large protein complex but are important in fine-tuning cellular responses to hormones and other extracellular signals. They influence processes like inflammation mood regulation and immune responses through their role in maintaining cAMP levels across different cell types.

Pathways

PDE4 enzymes occupy essential roles in the cAMP-dependent signaling pathway including the regulation of protein kinase A (PKA) activity. They interact with proteins like G-protein-coupled receptors (GPCRs) which activate the production of cAMP. This enzyme group also links to the MAPK/ERK pathway influencing cellular processes such as growth and differentiation.

PDE4 enzymes have implications in inflammatory diseases like asthma and rheumatoid arthritis. Their regulation of cAMP levels connects them to these disorders through modulation of inflammatory mediator release and immune cell function. In addition PDE4D has associations with neurodegenerative diseases like Alzheimer's disease acting through interactions with proteins involved in neuronal signaling and synaptic plasticity.