Cyclic AMP

2 Key excerpts on "Cyclic AMP"

• 

  eBook - ePub

  Handbook of Growth Factors (1994)

  Volume 1

  • Enrique Pimentel(Author)
  • 2017(Publication Date)
  • CRC Press

    (Publisher)

  Chapter 4

  Cyclic Nucleotides

  I. Introduction

  Cyclic nucleotides are purine derivative compounds that have a key role as second messengers in the mechanism of action of externally signaling agents including hormones, growth factors, regulatory peptides, and neurotransmitters. Two cyclic nucleotides, cyclic adenosine 3’,5’-monophosphate (Cyclic AMP or cAMP) and cyclic guanine 3’5’-monophosphate (cyclic GMP or cGMP), are involved in such functions, but the first of them, cAMP, is considered to be the most important cyclic nucleotide second messenger in mammalian cells.

  1 -6

  The possible role of a third cyclic nucleotide, cyclic cytidine 3’,5’-monophosphate (cCMP), in the regulation of cellular functions by external stimuli is controversial.7

  II. Cyclic AMP and the Adenylyl Cyclase System

  cAMP was discovered during a study on the effects of glycogenolytic hormones (glucagon and epinephrine) in liver slices and homogenates, which were associated with the accumulation of a heat-stable, dialyzable adenosine nucleotide.8 This molecule, in the presence of ATP, Mg2+ , and a cytoplasmic enzyme, was able to convert liver phosphorylase from an inactive precursor to an active form.9 The active substance, identified as cAMP, was shown to be biosynthesized from ATP by the action of a specific enzyme, adenylyl cyclase, which is an integral component of the plasma membrane.10 Methyl xanthines such as caffeine, aminophylline, and theophylline, can prevent the conversion of cAMP to an inactive noncyclic metabolite, 5’ adenosine monophosphate (5’ AMP), which is catalyzed by cAMP phosphodiesterase.11 Thus, by prolonging the survival of cAMP, methyl xanthines produce physiological effects that resemble those of many hormones that activate adenylyl cyclase. It was further demonstrated that the activation of glycogen phosphorylase by cAMP depends on the stimulation of a protein kinase, the cAMP-dependent protein kinase (protein kinase A), which transfers the terminal phosphate of ATP to specific serine and/or threonine residues in the enzyme undergoing activation.12

  Sign up to read

  Learn more about book
• 

  eBook - ePub

  Biochemistry of Signal Transduction and Regulation

  • Gerhard Krauss(Author)
  • 2014(Publication Date)
  • Wiley-VCH

    (Publisher)
• Intracellular messenger substances can be formed and degraded again in specific enzyme reactions. Via enzymatic pathways, large amounts of messenger substances can be repeatedly and rapidly created and inactivated.
• Messenger substances, such as Ca2+ , may be stored in special storage organelles, from which they can be rapidly released by a signal.
• Messenger substances may be produced in a location-specific manner, and they may also be removed or inactivated according to their location. It is therefore possible for the cell to create signals that are spatially and temporally limited.

8.2 Cyclic AMP

Summary

The second messenger 3′,5′-Cyclic AMP (cAMP) is produced from ATP by the action of adenylyl cyclases, and is degraded by the action of phosphodiesterases. The signaling function of cAMP is based primarily on binding to protein kinase A (PKA), ion channels, and the transcription factor Epac. To a large part, signaling by cAMP is restricted to discrete locations at the cell membrane and intracellular membrane compartments where cAMP production, binding to its target proteins and cAMP degradation each occur within defined supramolecular complexes organized by specific anchoring proteins such as the A-kinase anchoring proteins (AKAPs).

3′,5′-Cyclic AMP (cAMP), which is produced from ATP by the action of adenylyl cyclases (ACs; see Section 7.7.1 and Figure 7.30), influences many cellular functions including gluconeogenesis, glycolysis, lipogenesis, muscle contraction, membrane secretion, learning processes, ion transport, differentiation, growth control, and apoptosis.

The concentration of cAMP is controlled primarily by two means, namely via new synthesis by ACs and via degradation by phosphodiesterases. Both enzymatic activities cooperate in forming cAMP gradients in the cell with specific temporal and local characteristics. An important feature of cAMP signaling is the colocalization of the enzymes of cAMP metabolism and the targets of cAMP. For example, ACs, phosphodiesterases and protein kinase A have been found to colocalize at the same subcellular sites, allowing for a precise control of cAMP formation, degradation, and target selectivity.