Phosphodiesterase


The function of cyclic nucleotide phosphodiesterase (PDE 4, 7, 8)
Figure 1. The pymol rendering of cAMP phosphodiesterase adapted from Kranz, M. et al. (2009) Bioorganic medicinal chemistry 17, 5336-5341
Figure 1. The pymol rendering of cAMP phosphodiesterase adapted from Kranz, M. et al. (2009) Bioorganic medicinal chemistry 17, 5336-5341
is to break the phosphodiester bond in the cAMP (which acts as secondary molecules). As a result, the phosphodiesterase acts as a down-regulates the cAMP.

There are different isoforms of phosphodiesterases, which may hydrolyze different substrates. PDE 4, 7, 8 are affected by the A2A receptor and hydrolyzes cAMP. There are other phosphodiesterases (PDE 5, 6, 9), which are able to hydrolyze both cAMP and cGMP (PDE1, 2, 3, 10 and 11).[1]

Active Site


The active site of the cyclic nucleotide phosphodiesterase consists of glutamine residue. Reactions are mediated by a “hydrophobic clamp” that holds the purine base tightly in the active site (the conserved residues of F820 and V782 on each side[2] .

Effects of Caffeine

Caffeine is proven to be a competative inhibitor of phosphodiesterase inhibitor. It Contain one or more rings that mimic the purine (adenine) in the cN substrate[3] . Partial inhibition of phosphodiesterase is necessary to increase the levels of cAMP. Increase in cAMP increases the activity of PKA, subsequently HSL and therefore up-regulating lipolysis.[4]


cAMP.png
Figure 2: Molecular Structure of cAMP. Drawn by Tenniso Yu using Chembio Draw


Pathway 2
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  1. ^ Iffland, A. (2005) Biochemistry (N. Y. ). 44, 8312
  2. ^ Francis, S., Sekhar, K., Ke, H., and Corbin, J. (2011). Handb. Exp. Pharmacol. 200, 93-133
  3. ^ Zhang, K. Y. J. (2004). Mol. Cell 15, 279
  4. ^ Beavo et al. (1970). Mol.Pharm.6, 597-603