What is an adenylyl cyclase?
The adenylyl cyclases mediate effects of hormones or other messengers from the outside of the cell membrane to corresponding messengers in the cell interior. They are so-called lyases, which as enzymes cleave specific bonds in molecules. They split, for example, PO bonds (bond between phosphorus and oxygen).
Their task is to catalyze the degradation of ATP to the second messenger cAMP. This is done using G proteins. G proteins are responsible for signal transduction (signal transduction) between receptors and second messenger systems. For this purpose, the adenylyl cyclases have specific domains with characteristic structure, which act as binding sites for ATP and G proteins.
This binding initiates the catalytic action of adenylyl cyclases to break down ATP into mAMP. The blueprints of the different adenylyl cyclases are different. Common to all but the corresponding domains. There are ten isoenzymes for human adenylyl cyclases, nine of which are membrane-bound and one occurs as compartmentalized cytosolic protein inside the cell.
Function, effect & tasks
The task of adenylyl cyclases is to relay signals from the outer cell membrane via second messenger to messenger substances inside the cell. This applies to all eukaryotic creatures. But also in prokaryotic bacteria, adenylyl cyclases play a role as signal carriers. Thus, the adenylyl cyclases are divided into three main classes.
Class I is effective in Gram-negative bacteria. Class II adenylyl cyclases play a major role in disease-causing bacteria. They depend on the protein calmodulin of the infected host organism. The largest class (class III) are the adenylyl cyclases found in all eukaryotic organisms. Here they mediate the action of hormones. For this purpose, a signal is transmitted from the hormones of the outer cell membrane to the messengers in the cell interior. These messengers then trigger the biochemical reactions that are initiated by the hormones.
In the process, the corresponding hormone binds to its receptor, which simultaneously releases a specific G protein. The G protein in turn stimulates or inhibits an adenylyl cyclase that immediately catalyses the formation of cAMP from ATP or inhibits the formation of cAMP. In the conversion of ATP into cAMP, a pyrophosphate with two phosphate groups forms simultaneously. The pyrophosphate immediately breaks down into two phosphates. This makes a back reaction to ATP impossible. The regulation of adenylyl cyclases thus takes place through the influence of G proteins. The cAMP formed has many functions in the organism. It activates the enzyme protein kinase A.
The protein kinase A in turn catalyzes the phosphorylation of various enzymes and thus regulates the metabolism. Phosphorylation activates or inhibits the corresponding enzymes. Whether it comes to activation or inhibition depends on the respective enzymes. Via the reaction chain hormone, receptor, G-protein release, adenylyl cyclase activation / inhibition, formation of cAMP from ATP and stimulation of protein kinase A, the effect of certain hormones is mediated to the target site.
These hormones and messengers include glucagon, ACTH, epinephrine, norepinephrine, dopamine, oxytocin, histamine and others. In addition to activating protein kinase A, cAMP also stimulates gene expression for some hormones and enzymes. This applies among other things to the hormones parathyroid hormone, vasoactive intestinal peptide (VIP) or somatostatin.
Education, occurrence, properties & optimal values
Adenylyl cyclases occur everywhere in the living nature. All eukaryotic and some prokaryotic organisms use adenylyl cyclases to produce the common second messenger cAMP. In eukaryotes, the adenylyl cyclases are located on the membrane surface of the body cells. From there they pass on the signals of hormones and certain messenger substances into the cell, where various reactions are triggered.
Diseases & Disorders
Defects and disturbances in the entire transmission system of signals can cause a variety of diseases. Genetic modifications to various enzymes involved, including adenylyl cyclases, play a major role here. There are even theories that assume that most diseases are due to defective signal transduction from the cell membrane into the cell interior.
Disease have both a decreased as well as an increased signal transduction from cell surface into the cell interior. Examples include the eye disease retinitis pigmentosa or the renal diabetes insipidus. Many endocrine diseases are based on reduced signal transduction. The same is true for heart failure. Increased signal transduction leads to permanently increased cAMP values. It comes to a constant excitement, which manifests itself in various diseases such as heart failure or psychological disorders.
In addition to heart failure, such disorders as addictions (eg alcoholism), schizophrenia, Alzheimer's, asthma and others may be favored. The influence of signal transduction disorders on the development of such diseases as diabetes mellitus, arteriosclerosis, hypertension or tumor growth is also being investigated. Autoimmune diseases, such as ulcerative colitis, may be due to defective signal transduction. In cholera, a bacterial toxin is produced which causes a permanent activation of adenylyl cyclase.
The cAMP level is therefore increased because the corresponding hormonally activated adenylyl cyclases are not inhibited. Also in whooping cough (pertussis) the mAMP level is increased. Here, the inhibition of the adenylyl cyclase inhibitory G protein is missing. This increases the concentration of adenylyl cyclases. Many genetic modifications to the enzymes (including adenylyl cyclases) can also cause or promote disease.