Adenylyl cyclase: Difference between revisions
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Adenylyl Cyclase is | Adenylyl Cyclase is an [[Enzyme|enzyme]] that catalysis the conversion of [[ATP|ATP]] into [[CAMP|Cyclic AMP]] ([[CAMP|cAMP]]), which acts as a [[Secondary messenger|secondary messenger]]. As the diagram shows below a pyrophosphate molecule is removed in this reaction. | ||
====== Adenylyl Cyclase ====== | |||
ATP --------------------------------> cAMP + PPi | |||
| |||
It's activity is altered through the binding of various [[Hormones|hormones]], [[Epinephrine|epinephrine]], [[Vasopressin|vasopressin]] and [[Glucagon|glucagon]] <ref>Heldin and Purton:(1996:223)</ref>, to the G-protein coupled receptor. cAMP in the cell binds to protein kinase A (PKA) activating it. Therefore, adenylyl cyclase has a major role in alterining the activity of enzymes within the cell depending on its own activity i.e how much cAMP it is producing. | |||
<u>'''Structure'''</u> | |||
It is an integral [[Membrane|membrane]] [[Proteins|protein]] that has the structure of two bundles of six [[Transmembrane|transmembrane]] segments and two catalytic domains that extend as loops into the [[Cytoplasm|cytoplasm]], these catalystic domains are also the site of calmodulin binding. | |||
The [[Enzyme|enzyme]] can exist in at least 9 isoforms that are regulated in different ways by different [[G-protein Coupled Receptor|G protein coupled receptors]]. These isoforms can be divided into three groups:<br>Types I, II and VIII can activated by GalphaS and Ca+/calmodulin howvever ALSO can be inhibited by byßy | |||
Types II, IV and VII can be activated by GalphaS and ßy | |||
Types V and VI inhibited by Galphai and free Ca+ | |||
'''<u>Role of cAMP</u>''' | |||
As mentioned above cAMP increases PKA activity, however PKA has different effect in the cells of different oragans. For instance: in adipose tissue epinephrine results in higher cAMP thus incraesed PKA activity and then the PKA phosphorylates the appropriate enzymes resulting in trigylceride hydrolysis. This is different in cardiac muscle where epinephrine activates PKA which phosphorylates proteins/enzymes for increased contraction rate. | |||
cAMP is also involved in EPAC (Exchange proteins directly activated by cAMP) proteins.<ref>British Journal of Pharmacology (2009) 158, 70-86</ref> | |||
'''<u></u>''' | |||
'''<u>Removal of cAMP</u>''' | |||
PK8 Phosphorylates [[Phosphodiesterase|Phosphodiesterase]] 3D, which lowers [[CAMP|cAMP]] concerntration in the cells through hydrolysis. PK8 also has a negative feedback effect on [[Protein Kinase A|PKA]], decreasing adenylyl cyclase activity as a result. This lowers [[CAMP|cAMP]] levels even more. | PK8 Phosphorylates [[Phosphodiesterase|Phosphodiesterase]] 3D, which lowers [[CAMP|cAMP]] concerntration in the cells through hydrolysis. PK8 also has a negative feedback effect on [[Protein Kinase A|PKA]], decreasing adenylyl cyclase activity as a result. This lowers [[CAMP|cAMP]] levels even more. | ||
=== | ====== '''cAMP Phosphodiesterase''' ====== | ||
cAMP + H2O ---------------------> 5'AMP + H+(proton) | |||
<u>'''Reference'''</u> | |||
<references /> | <references /> | ||
Revision as of 16:35, 8 November 2011
Adenylyl Cyclase is an enzyme that catalysis the conversion of ATP into Cyclic AMP (cAMP), which acts as a secondary messenger. As the diagram shows below a pyrophosphate molecule is removed in this reaction.
Adenylyl Cyclase
ATP --------------------------------> cAMP + PPi
It's activity is altered through the binding of various hormones, epinephrine, vasopressin and glucagon [1], to the G-protein coupled receptor. cAMP in the cell binds to protein kinase A (PKA) activating it. Therefore, adenylyl cyclase has a major role in alterining the activity of enzymes within the cell depending on its own activity i.e how much cAMP it is producing.
Structure
It is an integral membrane protein that has the structure of two bundles of six transmembrane segments and two catalytic domains that extend as loops into the cytoplasm, these catalystic domains are also the site of calmodulin binding.
The enzyme can exist in at least 9 isoforms that are regulated in different ways by different G protein coupled receptors. These isoforms can be divided into three groups:
Types I, II and VIII can activated by GalphaS and Ca+/calmodulin howvever ALSO can be inhibited by byßy
Types II, IV and VII can be activated by GalphaS and ßy
Types V and VI inhibited by Galphai and free Ca+
Role of cAMP
As mentioned above cAMP increases PKA activity, however PKA has different effect in the cells of different oragans. For instance: in adipose tissue epinephrine results in higher cAMP thus incraesed PKA activity and then the PKA phosphorylates the appropriate enzymes resulting in trigylceride hydrolysis. This is different in cardiac muscle where epinephrine activates PKA which phosphorylates proteins/enzymes for increased contraction rate.
cAMP is also involved in EPAC (Exchange proteins directly activated by cAMP) proteins.[2]
Removal of cAMP
PK8 Phosphorylates Phosphodiesterase 3D, which lowers cAMP concerntration in the cells through hydrolysis. PK8 also has a negative feedback effect on PKA, decreasing adenylyl cyclase activity as a result. This lowers cAMP levels even more.
cAMP Phosphodiesterase
cAMP + H2O ---------------------> 5'AMP + H+(proton)
Reference