Serotonin-N-acetyltransferase

The pineal gland appears also to play a role in maintaining the mammalian circadian cycle.1081-1083 The concentration of the pineal hormone melatonin (Fig. 27-11) as well as its precursor N-acetylserotonin and the enzyme serotonin N-acetyltransferase (Eq. 30-4) all fluctuate far more than do the concentrations of other metabolites during the 24-h cycle. These metabolites increase over 10-fold concentration at night and decrease by day. During the daytime the serotonin N-acyltransferase, which forms the precursor, is rapidly... 

Fig. 7.2-9 Proposed model for the regulation of serotonin N-acetyltransferase (AANAT) by phosphorylation.

The pineal gland appears also to play a role in maintaining the mammalian circadian cyde. The concentrahon of fhe pineal hormone melatonin (Fig. 27-11) as well as its precursor N-acetylserotonin and the enzyme serotonin N-acetyltransferase (Eq. 30-... 

Vasoactive intestinal polypeptide (VIP) stimulated basal serotonin N-acetyltransferase activity in rat pineals in organ culture and enhanced the effects of catecholamines in inducing the enzyme (Yuwiler 1983). 

Norepinephrine activating ar and P-adrenergic receptors rises the intracellular concentration of calcium ions ([Ca ]i) and cyclic adenosine monophosphate, respectively. The norepinephrine-induced rise in [Ca ]i potentiates the increase of cAMP evoked by P-adrenergic stimulation (Vanecek etal. 1985). cAMP finally activates serotonin N-acetyltransferase, the key enzyme in melatonin production. 

The N-acetylation of different aryl- and arylalkylamines, using acetyl-CoA as the acetyl donor, proceeds when catalyzed by acetyl-Co A arylamine N-acetyltransferase. A natural substrate is serotonin, which is converted to N-acetylserotonin in the pineal gland and other regions of the brain. 

Fig. 5 Tryptophrin is converted to 5-hydroxytryptophan by tryptophan hydroxylase (1). The production of serotonin in the next step is catalysed by 5-HTP decaiboxylase (a PLP-dependent enzyme). Serotonin is then acetylated to N-acetyl-serotonin by N-acetyltransferase (2). Melatonin is then produced via the action of hydroxyindole-O-methyltransferase (3)...

Serotonin, or 5-HT, is biosynthesized (3) from its dietary precursor L-tryptophan (Fig. 14.1). Serotonergic neurons contain tryptophan hydroxylase (L-tryptophan-5-monooxygenase) that converts tryptophan to 5-hydroxytryptophan (5-HTP) in what is the rate-limiting step in 5-HT biosynthesis and aromatic L-amino acid decarboxylase (previously called 5-HTP decarboxylase) that decarboxylates 5-HTP to 5-HT. This latter enzyme also is responsible for the conversion of L-DOPA to dopamine (see Chapter 12). The major route of metabolism for 5-HT is oxidative deamination by monoamine oxidase (MAO-A) to the unstable 5-hydroxyindole-3-acetaldehyde, which is either reduced to 5-hydroxytryptophol ( 15%) or oxidized to 5-hydroxyindole-3-acetic acid ( -85%). In the pineal gland, 5-HT is acetylated by 5-HT N-acetyltransferase to N-acetylserotonin, which undergoes O-methylation by 5-hydroxyindole-O-methyltransferase to melatonin. 

The oxidation of tryptophan yields serotine, decarboxylation gives tryptamine, the oxidation of which leads to the hormone sero-tonine, from serotonine arises N-acetylserotonine (by the action of N-acetyltransferase), which is the precursor of hormone melatonin, which arises by the action of hydroxyindol-O-methyltransferase (Figure 10.18). An overview of biogenic amines occurring in foods, their preciusors, biological activities and the main products of their transformation is shown in Table 10.22. 

---