Derivatives of nucleic acids that control the activity of several proteins within cells to regulate and coordinate metabolism. They are members of a group of molecules known as intracellular second messengers; their levels are regulated by hormones and neurotransmitters, which are the extracellular first messengers in a regulatory pathway. Cyclic nucleotides are found naturally in all living cells.
Two major forms of cyclic nucleotides are characterized: 3′,5′-cyclic adenosine monophosphate (cyclic AMP or cAMP) and 3′,5′-cyclic guanosine monophosphate (cyclic GMP or cGMP). Like all nucleotides, cAMP and cGMP contain three functional groups: a nitrogenous aromatic base (adenine or guanine), a sugar (ribose), and a phosphate. Cyclic nucleotides differ from other nucleotides in that the phosphate group is linked to two different hydroxyl (3′ and 5′) groups of the ribose sugar and hence forms a cyclic ring. This cyclic conformation allows cAMP and cGMP to bind to proteins to which other nucleotides cannot.
An increase in cAMP or cGMP triggered by hormones and neurotransmitters can have many different effects on any individual cell. The type of effect is dependent to some extent on the cellular proteins to which the cyclic nucleotides may bind. Three types of effector proteins are able to bind cyclic nucleotides: protein kinases, ion channels, and cyclic nucleotide phosphodiesterases.
Protein kinases are enzymes which are able to transfer a phosphate group to (phosphorylate) individual amino acids of other proteins. This action often changes the function of the phosphorylated protein. Ion channels are proteins found in the outer plasma membrane of some cells; binding of cyclic nucleotides to them can alter the flow of sodium ions across the cell membranes. Cyclic nucleotide phosphodiesterases are enzymes responsible for the degradation of cyclic nucleotides.
In bacteria, cAMP can bind to a fourth type of protein, which can also bind to deoxyribonucleic acid (DNA). This catabolite gene activator protein (CAP) binds to specific bacterial DNA sequences, stimulating the rate at which DNA is copied into ribonucleic acid (RNA) and increasing the amount of key metabolic enzymes in the bacteria.
In humans, cyclic nucleotides acting as second messengers play a key role in many vital processes and some diseases. For example, in the brain, cAMP and possibly cGMP are critical in the formation of both long-term and short-term memory. In the liver, cAMP coordinates the function of many metabolic enzymes to control the level of glucose and other nutrients in the bloodstream. See also Adenosine triphosphate (ATP); Enzyme; Nucleic acid; Nucleoprotein; Nucleotide; Protein.
