cAMP & cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A (PDE10A)

Function

• plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides
• can hydrolyze both cAMP & cGMP, but has higher affinity for cAMP & is more efficient with cAMP as substrate
• cAMP acts as an allosteric activator
• purine metabolism; 3',5'-cyclic AMP degradation; AMP from 3',5'-cyclic AMP: step 1/1
• purine metabolism; 3',5'-cyclic GMP degradation; GMP from 3',5'-cyclic GMP: step 1/1

nucleoside 3',5'-cyclic phosphate + H2O = nucleoside 5'-phosphate

Cofactor:

• binds 2 divalent metal cations per subunit
• site 1 may preferentially bind Zn+2
• site 2 has a preference for Mg+2 &/or Mn+2

Kinetic parameters:

• KM=56 nM for cAMP
• KM=4.4 uM for cGMP
• Vmax=507 nmol/min/mg enzyme for cAMP
• Vmax=1860 nmol/min/mg enzyme for cGMP

Inhibition:

• inhibited by dipyridamole & moderately by IBMX homodimer

Structure

• homodimer
• the tandem GAF domains bind cAMP, & regulates enzyme activity; binding of cAMP stimulates enzyme activity
• composed of a C-terminal catalytic domain containing two divalent metal sites & an N-terminal regulatory domain which contains one cyclic nucleotide-binding region
• belongs to the cyclic nucleotide phosphodiesterase family
• contains 2 GAF domains

Compartment

• cytoplasm
• located mostly in soluble cellular fractions

Alternative splicing

named isoforms=2; PDE10A1, PDE10A2

Expression

• abundant in the putamen & caudate nucleus
• abundant in testis
• moderately expressed in the thyroid gland, pituitary gland, thalamus & cerebellum

More general terms

• phosphodiesterase 10

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=10846
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:10846
• OMIM: https://mirror.omim.org/entry/610652
• UniProt: http://www.uniprot.org/uniprot/Q9Y233.html