Aralkylamine N-acetyltransferase

Aralkylamine N-acetyltransferase (AANAT) (EC 2.3.1.87), also known as arylalkylamine N-acetyltransferase or serotonin N-acetyltransferase (SNAT), is an enzyme that is involved in the day/night rhythmic production of melatonin, by modification of serotonin. It is in humans encoded by the ~2.5 kb AANAT gene containing four exons, located on chromosome 17q25. The gene is translated into a 23 kDa large enzyme. It is well conserved through evolution and the human form of the protein is 80% identical to sheep and rat AANAT. It is an acetyl-CoA-dependent enzyme of the GCN5-related family of N-acetyltransferases (GNATs). It may contribute to multifactorial genetic diseases such as altered behavior in sleep/wake cycle and research is on-going with the aim of developing drugs that regulate AANAT function. Aralkylamine N-acetyltransferase (AANAT) (EC 2.3.1.87), also known as arylalkylamine N-acetyltransferase or serotonin N-acetyltransferase (SNAT), is an enzyme that is involved in the day/night rhythmic production of melatonin, by modification of serotonin. It is in humans encoded by the ~2.5 kb AANAT gene containing four exons, located on chromosome 17q25. The gene is translated into a 23 kDa large enzyme. It is well conserved through evolution and the human form of the protein is 80% identical to sheep and rat AANAT. It is an acetyl-CoA-dependent enzyme of the GCN5-related family of N-acetyltransferases (GNATs). It may contribute to multifactorial genetic diseases such as altered behavior in sleep/wake cycle and research is on-going with the aim of developing drugs that regulate AANAT function. The systematic name of this enzyme class is acetyl-CoA:2-arylethylamine N-acetyltransferase. Other names in common use include: The officially accepted name is aralkylamine N-acetyltransferase. The AANAT mRNA transcript is mainly expressed in the central nervous system (CNS). It is detectable at low levels in several brain regions including the pituitary gland as well as in the retina. It is most highly abundant in the pineal gland which is the site of melatonin synthesis. Brain and pituitary AANAT may be involved in the modulation of serotonin-dependent aspects of human behavior and pituitary function. In the pinealocyte cells of the pineal gland, aralkylamine N-acetyltransferase is involved in the conversion of serotonin to melatonin. It is the penultimate enzyme in the melatonin synthesis controlling the night/day rhythm in melatonin production in the vertebrate pineal gland. Melatonin is essential for seasonal reproduction, modulates the function of the circadian clock in the suprachiasmatic nucleus, and influences activity and sleep. Due to its important role in circadian rhythm, AANAT is subjected to extensive regulation that is responsive to light exposure (see Regulation). It may contribute to multifactorial genetic diseases such as altered behavior in sleep/wake cycle and mood disorders. The primary chemical reaction that is catalyzed by aralkylamine N-acetyltransferase uses two substrates, acetyl-CoA and serotonin. AANAT catalyzes the transfer of the acetyl group of Acetyl-CoA to the primary amine of serotonin, thereby producing CoA and N-acetylserotonin. In humans, other endogenous substrates of the enzyme include specific trace amine neuromodulators, namely phenethylamine, tyramine, and tryptamine, in turn forming N-acetylphenethylamine, N-acetyltyramine, and N-acetyltryptamine. In the biosynthesis of melatonin, N-acetylserotonin is further methylated by another enzyme, N-acetylserotonin O-methyltransferase (ASMT) to generate melatonin. The N-acetyltransferase reaction has been suggested to be the rate-determining step, and thus Serotonin N-acetyltransferase has emerged as a target for inhibitor design (see below). AANAT obeys an ordered ternary-complex mechanism. The substrates bind sequentially (ordered) with acetyl-CoA binding to the free enzyme followed by the binding of serotonin to form the ternary complex. After the transfer of the acetyl group has occurred, the products are orderly released with N-acetyl-serotonin first and CoA last.