Cyclic Nucleotides: Synthesis by Adenylyl and Guanylyl Cyclases

Abstract

Cyclic-3' ,5'-adenosine monophosphate (cAMP) and cyclic-3' ,5'-guanosine monophosphate (cGMP) are second messengers in intracellular signaling cascades. The intracellular levels of these cyclic nucleotides are regulated by two enzyme systems. Adenylyl cyclase and guanylyl cyclase synthesize cAMP and cGMP, respectively, and cyclic nucleotide phosphodiesterase hydrolyzes these cyclic nucleotides. Each cyclase system synthesizes only one of these cyclic nucleotides; however, various kinds of phosphodi-esterases hydrolyze both cAMP and cGMP (see chapter on cyclic nucleotide phosphodiesterases). Complete details of the functional relationship between cyclase systems and phosphodiesterase systems in most cells remain unclear. However, it is evident that a wide variety of exogenous stimuli, such as hormones, neurotransmitters, and physical and chemical signals, controls the intracellular level of these cyclic nucleotides by regulating these enzyme systems directly or indirectly. The physiological effects of these cyclic nucleotides are exerted through binding to a number of various proteins, including cyclic nucleotide-dependent protein kinases, cyclic nucleotide-gated channels, and cyclic nucleotide-regulated (or-bound) phosphodiesterases (see these chapters). Thus, the phosphorylated state of various proteins and the concentrations of ions and cyclic nucleotides in cells are controlled by extracellular signals. The presence of these cyclic nucleotide-binding proteins indicates the essential roles of these cyclic nucleotides in the organization of cellular functions. The basic concepts of adenylyl and guanylyl cyclase functions are described in this chapter.