Adenylate cyclase is a
lyaseIn biochemistry, a lyase is an enzyme that catalyzes the breaking of various chemical bonds by means other than hydrolysis and oxidation, often forming a new double bond or a new ring structure...
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
. It is a part of the cAMP-dependent pathway
There are ten known adenylate cyclases in
mammalMammals are a class of vertebrate animals whose females are characterized by the possession of mammary glands while both males and females are characterized by sweat glands, hair, three middle ear bones used in hearing, and a neocortex region in the brain.Mammals are divided into three main...
s:
- ADCY1
Adenylate cyclase type 1 is an enzyme that in humans is encoded by the ADCY1 gene.-Further reading:...
- ADCY2
Adenylate cyclase type 2 is an enzyme that in humans is encoded by the ADCY2 gene.-Further reading:...
- ADCY3
Adenylate cyclase type 3 is an enzyme that in humans is encoded by the ADCY3 gene.-Further reading:...
- ADCY4
Adenylate cyclase type 4 is an enzyme that in humans is encoded by the ADCY4 gene.-Further reading:...
- ADCY5
Adenylate cyclase type 5 is an enzyme that in humans is encoded by the ADCY5 gene.-Further reading:...
- ADCY6
Adenylate cyclase type 6 is an enzyme that in humans is encoded by the ADCY6 gene.-Further reading:...
- ADCY7
Adenylate cyclase type 7 is an enzyme that in humans is encoded by the ADCY7 gene.-Further reading:...
- ADCY8
Adenylate cyclase type 8 is an enzyme that in humans is encoded by the ADCY8 gene.-Further reading:...
- ADCY9
Adenylate cyclase type 9 is an enzyme that in humans is encoded by the ADCY9 gene.-Further reading:...
- ADCY10
Adenylate cyclase 10 also known as ADCY10 is an enzyme which in humans is encoded by the ADCY10 gene.- Function :The protein encoded by this gene belongs to a distinct class of mammalian adenylyl cyclase that is soluble and insensitive to G protein or forskolin regulation...
Adenylate cyclase
catalyzesCatalysis is the process in which the rate of a chemical reaction is either increased or decreased by means of a chemical substance known as a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. The catalyst may participate...
the conversion of
ATPAdenosine-5'-triphosphate is a multifunctional nucleotide that plays an important role in cell biology as a coenzyme, that is, the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
to 3',5'-cyclic AMP (cAMP) and
pyrophosphateIn chemistry, the anion, the salts, and the esters of pyrophosphoric acid are called pyrophosphates. Pyrophosphates were originally prepared by heating phosphates: the prefix pyro- derived from Greek, means "fire" in this context. Pyrophosphates are good complexing agents and have many uses in...
.
thumb
cAMP (cyclic adenosine monophosphate) is an important molecule in
eukaryoticA eukaryote is an organism whose cells contain complex structures enclosed within membranes. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear envelope, within which the genetic material is carried...
signal transductionIn biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another. Most processes of signal transduction involve ordered sequences of biochemical reactions inside the cell, which are carried out by enzymes and activated by second messengers,...
, a so-called second messenger.
Adenylate cyclase is a
lyaseIn biochemistry, a lyase is an enzyme that catalyzes the breaking of various chemical bonds by means other than hydrolysis and oxidation, often forming a new double bond or a new ring structure...
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
. It is a part of the cAMP-dependent pathway
Types
There are ten known adenylate cyclases in
mammalMammals are a class of vertebrate animals whose females are characterized by the possession of mammary glands while both males and females are characterized by sweat glands, hair, three middle ear bones used in hearing, and a neocortex region in the brain.Mammals are divided into three main...
s:
- ADCY1
Adenylate cyclase type 1 is an enzyme that in humans is encoded by the ADCY1 gene.-Further reading:...
- ADCY2
Adenylate cyclase type 2 is an enzyme that in humans is encoded by the ADCY2 gene.-Further reading:...
- ADCY3
Adenylate cyclase type 3 is an enzyme that in humans is encoded by the ADCY3 gene.-Further reading:...
- ADCY4
Adenylate cyclase type 4 is an enzyme that in humans is encoded by the ADCY4 gene.-Further reading:...
- ADCY5
Adenylate cyclase type 5 is an enzyme that in humans is encoded by the ADCY5 gene.-Further reading:...
- ADCY6
Adenylate cyclase type 6 is an enzyme that in humans is encoded by the ADCY6 gene.-Further reading:...
- ADCY7
Adenylate cyclase type 7 is an enzyme that in humans is encoded by the ADCY7 gene.-Further reading:...
- ADCY8
Adenylate cyclase type 8 is an enzyme that in humans is encoded by the ADCY8 gene.-Further reading:...
- ADCY9
Adenylate cyclase type 9 is an enzyme that in humans is encoded by the ADCY9 gene.-Further reading:...
- ADCY10
Adenylate cyclase 10 also known as ADCY10 is an enzyme which in humans is encoded by the ADCY10 gene.- Function :The protein encoded by this gene belongs to a distinct class of mammalian adenylyl cyclase that is soluble and insensitive to G protein or forskolin regulation...
Reaction
Adenylate cyclase
catalyzesCatalysis is the process in which the rate of a chemical reaction is either increased or decreased by means of a chemical substance known as a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. The catalyst may participate...
the conversion of
ATPAdenosine-5'-triphosphate is a multifunctional nucleotide that plays an important role in cell biology as a coenzyme, that is, the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
to 3',5'-cyclic AMP (cAMP) and
pyrophosphateIn chemistry, the anion, the salts, and the esters of pyrophosphoric acid are called pyrophosphates. Pyrophosphates were originally prepared by heating phosphates: the prefix pyro- derived from Greek, means "fire" in this context. Pyrophosphates are good complexing agents and have many uses in...
.
thumb
cAMP (cyclic adenosine monophosphate) is an important molecule in
eukaryoticA eukaryote is an organism whose cells contain complex structures enclosed within membranes. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear envelope, within which the genetic material is carried...
signal transductionIn biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another. Most processes of signal transduction involve ordered sequences of biochemical reactions inside the cell, which are carried out by enzymes and activated by second messengers,...
, a so-called second messenger. Adenylate cyclase can be activated or inhibited by
G proteinG proteins, short for guanine nucleotide-binding proteins, are a family of proteins involved in second messenger cascades.G proteins are so called because they function as "molecular switches," alternating between an inactive guanosine diphosphate and active guanosine triphosphate bound state,...
s, which are coupled to membrane receptors and thus can respond to hormonal or other stimuli. Following activation of adenylate cyclase, the resulting cAMP acts as a second messenger by interacting with and regulating other proteins such as protein kinase A and
cyclic nucleotide-gated ion channelsHyperpolarization-activated cyclic nucleotide gated channels are proteins that serve as ion channels across the plasma membrane of heart and brain cells. HCN channels are sometimes referred to as “pacemaker channels” because they help to generate rhythmic activity within groups of heart and brain...
.
Photoactivatable adenylate cyclase (PAC) was discovered in
E. gracilis and can be expressed in other organisms through genetic manipulation. Shining blue light on a cell containing PAC activates it and abruptly increases the rate of conversion of ATP to cAMP. This is a useful technique for researchers in neuroscience because it allows them to quickly increase the intracellular cAMP levels in particular neurons, and to study the effect of that increase in neural activity on the behavior of the organism. For example, PAC expression in certain neurons has been shown to alter the grooming behavior in fruit flies exposed to blue light
http://www.nature.com/nmeth/journal/v4/n1/abs/nmeth975.html. Researchers also use channelrhodopsin-2 in a similar fashion.
Structure
Adenylyl cyclase is a transmembrane
proteinProteins are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues...
. It passes through the plasma membrane twelve times.
The important parts for its function are located in the
cytoplasmThe cytoplasm is the part of a cell that is enclosed within the cell membrane. In eukaryotic cells, the cytoplasm contains organelles, such as mitochondria, which are filled with liquid that is kept separate from the rest of the cytoplasm by biological membranes. The contents of the cell nucleus...
and can be subdivided into the N-terminus, C1a, C1b, C2a, and C2b.
The C1 region exists between transmembrane helices six and seven, and the C2 region follows transmembrane helix 12.
The C1a and C2a domains form a catalytic dimer where ATP binds and is converted to cAMP.
Regulation
Adenylate cyclase is stimulated by
G proteinG proteins, short for guanine nucleotide-binding proteins, are a family of proteins involved in second messenger cascades.G proteins are so called because they function as "molecular switches," alternating between an inactive guanosine diphosphate and active guanosine triphosphate bound state,...
s, and by
forskolinForskolin is a labdane diterpene that is produced by the Indian Coleus plant . Forskolin is commonly used to raise levels of cyclic AMP in the study and research of cell physiology. Forskolin resensitizes cell receptors by activating the enzyme adenylyl cyclase and increasing the intracellular...
, as well as other class-specific substrates:
- Isoforms I, III and VIII are also stimulated by Ca2+
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft grey alkaline earth metal, and is the fifth most abundant element by mass in the Earth's crust...
/calmodulinthumb|200px|Flexibility of Calmodulin. Calmodulin can bind to calmodulin-dependent-protein kinase II-alpha ; it can bind to myosine light chain ; it can bind to edema factor toxin from the anthrax bacteria...
.
- Isoforms V and VI are inhibited by Ca2+ in a calmodulin-independent manner.
In
neuronA neuron is an excitable cell in the nervous system that processes and transmits information by electrochemical signaling. Neurons are the core components of the brain, the vertebrate spinal cord, the invertebrate ventral nerve cord, and the peripheral nerves...
s, adenylate cyclases are located next to calcium
ion channelIon channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of all living cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s for faster reaction to Ca
2+ influx; they are suspected of playing an important role in learning processes. This is supported by the fact that adenylate cyclases are
coincidence detectors, meaning that they are activated only by several different signals occurring together.