Department of Genetics and Marine Biotechnology, Institute of Oceanology, Polish Academy of Sciences, Powstańców Warszawy 55 Str., 81-712 Sopot, Poland.
Department of Marine Physics, Institute of Oceanology, Polish Academy of Sciences, Powstańców Warszawy 55 Str., 81-712 Sopot, Poland.
Comp Biochem Physiol A Mol Integr Physiol. 2024 Nov;297:111731. doi: 10.1016/j.cbpa.2024.111731. Epub 2024 Aug 24.
The classic melatonin biosynthesis pathway (Mel; N-acetyl-5-methoxytryptamine) involves two consecutive enzymatic steps that are decisive in hormone production: conversion of serotonin (5-hydroxytryptamine; 5-HT) to N-acetylserotonin (NAS) and the methylation of the last compound to Mel. This pathway requires the activity of the enzymes: the first is of the category of N-acetyltransferases (AANAT, SNAT, or NAT) and the second is N-acetylserotonin O-methyltransferase (ASMT; also known as HIOMT). However, quite recently, new information has been provided on the possibility of an alternative Mel synthesis pathway; it would include a two-step action by these enzymes, but in reverse order, where ASMT (or ASMTL, the enzyme related to ASMT) methylates 5-HT to 5-methoxytryptamine (5-MT), and then the last compound is acetylated by an enzyme of the category of N-acetyltransferases to Mel. In our study on the activity of enzymes in the Mel biosynthesis pathway in flounder skin, we have found an increase in 5-MT level, as a result of the increase in 5-HT concentration, which is followed by a growing concentration of Mel. However, we have not found any increase in Mel concentration, despite an increase in NAS in the samples. Our data strongly suggest an alternative way of Mel production in flounder skin in which 5-HT is first methylated to 5-MT, which is then acetylated to Mel.
经典的褪黑素生物合成途径(Mel;N-乙酰-5-甲氧基色胺)涉及两个连续的酶促步骤,这对于激素的产生至关重要:将血清素(5-羟色胺;5-HT)转化为 N-乙酰血清素(NAS),以及最后一种化合物的甲基化生成 Mel。这条途径需要以下两种酶的活性:第一种酶属于 N-乙酰转移酶(AANAT、SNAT 或 NAT)类别,第二种酶是 N-乙酰血清素 O-甲基转移酶(ASMT;也称为 HIOMT)。然而,最近有新的信息表明,褪黑素合成的另一种途径是可能的;它将包括这两种酶的两步作用,但顺序相反,其中 ASMT(或 ASMTL,与 ASMT 相关的酶)将 5-HT 甲基化为 5-甲氧基色胺(5-MT),然后最后一种化合物被 N-乙酰转移酶类别的酶乙酰化为 Mel。在我们对鲽鱼皮肤中褪黑素生物合成途径的酶活性的研究中,我们发现 5-HT 浓度的增加导致 5-MT 水平升高,随后 Mel 的浓度也随之升高。然而,尽管样品中 NAS 增加,但我们没有发现 Mel 浓度的增加。我们的数据强烈表明,在鲽鱼皮肤中,褪黑素的产生存在一种替代途径,即 5-HT 首先被甲基化为 5-MT,然后被乙酰化为 Mel。