Arylalkylamine N-Acetyltransferase: “the Timezyme”

Abstract

Arylalkylamine N-acetyltransferase controls daily changes in melatonin production by the pineal gland and thereby plays a unique role in biological timing in vertebrates. Arylalkylamine N-acetyltransferase is also expressed in the retina, where it may play other roles in addition to signaling, including neurotransmission and detoxification. Large changes in activity reflect cyclic 3,5-adenosine monophosphate-dependent phosphorylation of arylalkylamine N-acetyltransferase, leading to formation of a regulatory complex with 14-3-3 proteins. This activates the enzyme and prevents proteosomal proteolysis. The conserved features of regulatory systems that control arylalkylamine N-acetyltransferase are a circadian clock and environmental lighting.Arylalkylamine N-acetyltransferase (AANAT; EC 2.1.3.87) 2 plays a unique role in vertebrate biology by controlling the rhythmic production of melatonin in the pineal gland ( Fig. 1) (1). Activity increases 10-to 100-fold at night, causing an increase in the production and release of melatonin. The dynamics of AANAT activity are remarkable: the doubling time is ϳ15 min at night, and the halving time of the decrease that follows a night 3 light transition is ϳ3.5 min (2, 3). Circulating melatonin levels parallel changes in synthesis and release, due to rapid clearance by the liver (1).The rhythmic pattern of activity in the melatonin pathway is a conserved feature of vertebrate biology, consistent with the role of melatonin as the vertebrate hormone of time, i.e. high levels signal night and low levels signal day. Although this signaling pattern is conserved, it is used in a variety of species-dependent ways to optimally control seasonal and daily changes in physiology (1). The unique role that AANAT plays in vertebrate time keeping justifies the title of "the Timezyme." Our knowledge of the biological chemistry of AANAT is summarized in this overarching review. Aanat Genes and EvolutionThe AANAT Family-Aanat and Aanat homologs form the AANAT family, which is part of the large Gcn5-related acetyltransferase (GNAT) superfamily (4, 5). All GNAT family members share common structural features associated with acetyl coenzyme A (AcCoA) binding; in addition, each member family has unique features reflecting substrate specificity for each of a wide range of substrates (e.g. aminoglycosides, diamines, puromycin, histones, and arylalkylamines). The GNAT superfamily also includes another arylalkylamine N-acetyltransferase family, represented by dopamine N-aceyltransferase (Dat), which is expressed in Drosophila melanogaster (6). Dat is not involved time keeping; rather, it functions in cuticle sclerotization and neurotransmission (6). DAT and AANAT family members have not been found in the same genome.AANAT family members have only been found in Grampositive bacteria, fungi, algae, cephalochordates, and vertebrates; family members are not found in higher plants, insects, nematodes, or urochordates (7). This distribution may be explained by the initial appearance of the ancestral Aanat in ...

MELATONIN-SYNTHESIZING ENZYMES IN PINEAL, RETINA, LIVER, AND GUT OF THE GOLDFISH (CARASSIUS): mRNA EXPRESSION PATTERN AND REGULATION OF DAILY RHYTHMS BY LIGHTING CONDITIONS

“…This goldfish AANAT-2 deduced amino acid sequence shows more that 90% identity with Aanat-2 sequences from other fish species such as zebrafish, seabream, rainbow trout or pike. Moreover, characteristic binding motifs, phosphorylation sites and conserved regions of the AANAT family (Ganguly et al 2002;Klein, 2007) are identified in the goldfish sequence, supporting the homology of the encoded protein.…”

“…Moreover, as occurs in zebrafish (Gothilf et al, 1999), a positive signal for AANAT-2 transcript is also found in goldfish retina, in spite of the general acceptance that Aanat-2 is more specifically expressed in the pineal organ of teleost (Klein, 2007, Falcon, 2009. One interesting evidences from present results is the peripheral expression of both enzymes, AANAT-2 and HIOMT-2, which supports MEL synthesis in such peripheral locations.…”

“…A highly conserved feature in vertebrates is the daily rhythmic pattern of MEL synthesis, which is determined by rhythms in AANAT activity, protein amount and, in some cases, gene expression, resulting in a nocturnal increase of this neurohormone (Iuvone et al, 2005, Klein, 2007. Pineal and retinal expression of Aanats has been reported in several teleost adults Zilberman-Peled et al, 2004;2006) and in photoreceptive organs of embryos of chum salmon (Shi et al, 2004), turbot (Vuilleumier et al, 2007) and in the sole (Isorna et al, 2009), and a species-dependent expression pattern has been evidenced.…”

“…The functional role played by AANAT-2 in these locations, is of great interest and several possibilities, apart from the MEL synthesis, can be suggested, as the reduction of the oxidative formation of aldehydes of serotonin and other arylalkylamines (Bernard et al, 1995;Coon et al, 2002) and/or a detoxification role, as it is considered the original function of this enzyme Klein, 2007). Nevertheless, in addition to the expected Hiomt expression in goldfish pineal and retina, where MEL synthesis is well documented in vivo and in vitro (Iigo et al, 1991;1997), we found positive signals for HIOMT transcripts in gonads and, to a lesser extent, in liver and gut.…”

Diurnal and seasonal changes in <i>IL-6</i> and <i>IL-18</i> gene expression in blood leukocytes of male chickens with experimental peritonitis: the impact of lighting conditions and melatonin

“…It is generally accepted that the diurnal profile of the blood melatonin concentration results from daily variations in the activity of pineal arylalkylamine-N-acetyltransferase (AANAT; E.C.2.3.1.87), a key enzyme in melatonin biosynthesis (Klein, 2007). The daily profile of AANAT activity in chickens was found to be affected by the season, regardless of artificial LD 12:12 conditions imposed from the day of hatch Piesiewicz et al, 2012b).…”