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A cyclic nucleotide (cNMP) is a single-phosphate nucleotide with a cyclic bond arrangement between the sugar and phosphate groups. Like other nucleotides, cyclic nucleotides are composed of three functional groups: a sugar, a nitrogenous base, and a single phosphate group. As can be seen in the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) images, the 'cyclic' portion consists of two bonds between the phosphate group and the 3' and 5' hydroxyl groups of the sugar, very often a ribose. Their biological significance includes a broad range of protein-ligand interactions. They have been identified as secondary messengers in both hormone and ion-channel signalling in eukaryotic cells, as well as allosteric effector compounds of DNA binding proteins in prokaryotic cells. cAMP and cGMP are currently the most well documented cyclic nucleotides, however there is evidence that cCMP (cytosine) is also involved in eukaryotic cellular messaging. The role of cyclic uridine monophosphate (cUMP) is even less well known. Discovery of cyclic nucleotides has contributed greatly to the understanding of kinase and phosphatase mechanisms, as well as protein regulation in general. Although more than 50 years have passed since their initial discovery, interest in cyclic nucleotides and their biochemical and physiological significance continues. ==History== The understanding of the concept of second messengers, and in particular the role of cyclic nucleotides and their ability to relay physiological signals to a cell, has its origins in the research of glycogen metabolism by Carl and Gerty Cori, for which they were awarded a Nobel Prize in Physiology or Medicine in 1947.〔 A number of incremental but important discoveries through the 1950s added to their research, primarily focusing on the activity of glycogen phosphorylase in dog liver. Glycogen phosphorylase catalyzes the first step in glycogenolysis, the process of breaking glycogen into its substituent glucose parts.〔 Earl Sutherland investigated the effect of the hormones adrenaline and glucagon on glycogen phosphorylase, earning him the Nobel Prize in Physiology or Medicine in 1971.〔 In 1956 Edwin Krebs and Edmond Fischer discovered that adenosine triphosphate (ATP) is required for the conversion of glycogen phosphorylase b to glycogen phosphorylase a. While investigating the action of adrenaline on glycogenolysis the next year, Sutherland and Walter Wosilait reported that inorganic phosphate is released when the enzyme liver phosphorylase is inactivated; but when it is activated, it incorporates a phosphate.〔 The “active factor” that the hormones produced〔 was finally purified in 1958, and then identified as containing a ribose, a phosphate, and an adenine in equal ratios. Further, it was proved that this factor reverted to 5’-AMP when it was inactivated.〔 Evgeny Fesenko, Stanislav Kolesnikov, and Arkady Lyubarsky discovered in 1985 that cyclic guanosine monophosphate (cGMP) can initiate the photoresponse in rods. Soon after, the role of cNMP in gated ion channels of chemosensitive cilia of olfactory sensory neurons was reported by Tadashi Nakamura and Geoffrey Gold. In 1992 Lawrence Haynes and King-Wai Yau uncovered cNMP’s role in the light-dependent cyclic-nucleotide-gated channel of cone photoreceptors.〔 By the end of the decade, the presence of two types of intramembrane receptors was understood: Rs (which stimulates cyclase) and Ri (which inhibits cyclase). Wei-Jen Tang and James Hurley reported in 1998 that adenylyl cyclase, which synthesizes cAMP, is regulated not only by hormones and neurotransmitters, but also by phosphorylation, calcium, forskolin, and guanine nucleotide-binding proteins (G proteins).〔 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Cyclic nucleotide」の詳細全文を読む スポンサード リンク
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