AANAT - Aralkylamine N-Acetyltransferase |Elisa - Clia - Antibody - Protein

Background:

AANAT, ,Aralkylamine N-acetyltransferase (AANAT), also known as arylalkylamine N-acetyltransferase is an enzyme encoded by the AANAT gene. It plays a critical role in the biosynthesis of melatonin, a hormone involved in regulating the circadian rhythm and other physiological processes. AANAT catalyzes the transfer of an acetyl group from acetyl-CoA to serotonin, the precursor molecule of melatonin, fundamental in coordination of daily and seasonal rhythms. Activity may increase 10- to 100-fold at night, causing an increase in the production and release of melatonin. Dysregulation of AANAT activity or melatonin synthesis can have implications for sleep disorders, circadian rhythm disorders, and psychiatric conditions

Structure:

AANAT is a soluble enzyme that belongs to the GNAT (GCN5-related N-acetyltransferase) superfamily of enzymes. It consists of a catalytic domain that binds both the acetyl-CoA cofactor and the substrate serotonin. AANAT undergoes conformational changes upon substrate binding, facilitating the acetylation reaction.

Classification and Subtypes:

AANAT is classified as an arylalkylamine N-acetyltransferase and is part of the GNAT superfamily. While there are no known subtypes of AANAT in humans, its enzymatic activity is conserved across various species, from bacteria to mammals.

Function and Biological Significance:

1. Melatonin Biosynthesis: AANAT is the rate-limiting enzyme in the biosynthesis of melatonin. It catalyzes the conversion of serotonin to N-acetylserotonin, which is subsequently converted to melatonin by the enzyme hydroxyindole-O-methyltransferase (HIOMT). Melatonin plays a crucial role in regulating the circadian rhythm, sleep-wake cycles, and other physiological processes.
2. Circadian Rhythm Regulation: AANAT activity is under tight regulation by the circadian clock, with peak activity occurring at night in response to signals from the suprachiasmatic nucleus (SCN) of the brain. This diurnal rhythm of AANAT activity ensures the appropriate synthesis and secretion of melatonin in response to changes in light-dark cycles.
3. Neurotransmitter Metabolism: AANAT-mediated metabolism of serotonin contributes to the regulation of neurotransmitter levels in the brain. Serotonin is involved in mood regulation, appetite, and other physiological functions, and its metabolism by AANAT may influence neurotransmitter signaling pathways.

Relevant Clinical Issues:

1. Sleep Disorders: Dysregulation of melatonin synthesis, including alterations in AANAT activity, has been implicated in sleep disorders such as insomnia, delayed sleep phase disorder, and seasonal affective disorder (SAD). Modulating AANAT activity or melatonin levels may offer therapeutic approaches for managing these conditions.
2. Circadian Rhythm Disorders: Genetic mutations or environmental factors affecting AANAT expression or activity can disrupt the circadian rhythm and lead to circadian rhythm sleep-wake disorders (CRSWDs). Pharmacological interventions targeting melatonin synthesis or administration of exogenous melatonin may help regulate circadian rhythms in affected individuals.
3. Psychiatric Disorders: Dysregulation of serotonin metabolism and melatonin synthesis has been implicated in psychiatric disorders such as depression, anxiety, and bipolar disorder. AANAT activity may be altered in these conditions, contributing to disturbances in mood and behavior.