Prostaglandylinositol cyclic phosphate, the natural antagonist of cyclic AMP.
Adrenergic alpha-receptor
cyclic AMP
inositol phosphates
insulin action
prostaglandin E
protein kinase A
protein phosphorylation
protein ser/thr phosphatase
regulation of metabolism
signal-transduction
Journal
IUBMB life
ISSN: 1521-6551
Titre abrégé: IUBMB Life
Pays: England
ID NLM: 100888706
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
26
06
2020
revised:
29
07
2020
accepted:
04
08
2020
pubmed:
8
9
2020
medline:
23
11
2021
entrez:
7
9
2020
Statut:
ppublish
Résumé
While searching for a counterpart to cyclic AMP, a new compound was found to inhibit adenylate cyclase. It was identified as prostaglandyl-(15-4')-myo-inositol (1':2'-cyclic)-phosphate (cyclic PIP). The substrates for its biosynthesis are prostaglandin E (PGE) and the novel inositol phosphate, guanosine diphospho-4-myo-inositol 1:2-cyclic phosphate (n-IP). The basic regulatory properties of cyclic PIP are to inhibit dose-dependently protein kinase A (PKA) and to seven-fold activate protein ser/thr phosphatase holoenzyme. These regulations occur as rapidly as the activation of PKA by cyclic AMP. Such regulatory properties are essential for the meticulous regulation of the equilibrium between the phospho- and de-phospho-form of interconvertible enzymes. The synthesis of cyclic PIP is stimulated by insulin and noradrenaline (α-receptor action). The insulin-stimulated cyclic PIP synthase is active in a tyrosine-phosphorylated state. A comparable characterization of the adrenaline-stimulated cyclic PIP synthase is still incomplete. In streptozotocin-diabetic rats, the hormonal stimulation of cyclic PIP synthesis decreases with time. Cyclic PIP synthesis is activated by biguanides as metformin two to four-fold and by antihypertensive drugs two-fold. Inhibition of cyclic PIP synthesis leads to a metabolic state as observed in early-stage type-2 diabetes. In summary, all living cells synthesize cyclic PIP, which switches on anabolism, whereas cyclic AMP triggers catabolism.
Substances chimiques
Inositol Phosphates
0
Prostaglandins E
0
prostaglandin-inositol cyclic phosphate
0
Cyclic AMP
E0399OZS9N
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2282-2289Informations de copyright
© 2020 International Union of Biochemistry and Molecular Biology.
Références
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