dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A (cAMP & cGMP phosphodiesterase 11A, PDE11A)

Function

• role in signal transduction by regulating intracellular concentration of cyclic nucleotides cAMP & cGMP
• catalyzes hydrolysis of both cAMP & cGMP to 5'-AMP & 5'-GMP, respectively
• cGMP acts as an allosteric activator

guanosine 3',5'-cyclic phosphate + H2O

<-->

guanosine 5'-phosphate

adenosine 3',5'-cyclic phosphate + H2O

<-->

adenosine 5'-phosphate

Cofactor: divalent cations

Inhibition:

• 3-isobutyl-1-methylxanthine (IBMX)
• zaprinast
• dipyridamole
• weakly inhibited by Sildenafil (Viagra) & Tadalafil (Cialis) <probably absent from testis, thus not likely biologically relevant to erectile dysfunction>

Kinetic parameters:

• KM=3.0 uM for cAMP (isoform 1)
• KM=1.4 uM for cGMP (isoform 1)
• Vmax=270 pmol/min/ug enzyme with cAMP as substrate (isoform 1)
• Vmax=120 pmol/min/ug enzyme with cGMP as substrate (isoform 1)

Structure

• belongs to the cyclic nucleotide phosphodiesterase family
• contains 2 GAF domains
  • tandem GAF domains bind cGMP, & regulate enzyme activity

Compartment

cytoplasm

Alternative splicing

named isoforms=4

Expression

• isoform 1 is present in prostate, pituitary, heart, liver not present in testis nor in penis
• isoform 2 may be expressed in testis
  • isoform 4 is expressed in adrenal cortex

Pathology

• defects in PDE11A are a cause of adrenocortical hyperplasia

More general terms

• phosphodiesterase

Database

• OMIM: https://mirror.omim.org/entry/604961
• UniProt: http://www.uniprot.org/uniprot/Q9HCR9.html