Last update 01 Nov 2024

PNMT

Last update 01 Nov 2024

Basic Info

Synonyms

Noradrenaline N-methyltransferase, PENT, Phenylethanolamine N-methyltransferase

+ [2]

Introduction

Catalyzes the transmethylation of nonepinephrine (noradrenaline) to form epinephrine (adrenaline), using S-adenosyl-L-methionine as the methyl donor (PubMed:20496117). Other substrates include phenylethanolamine and octopamine (PubMed:8812853, PubMed:16363801, PubMed:16277617). Also methylates normetanephrine (By similarity).

100 Clinical Results associated with PNMT

100 Translational Medicine associated with PNMT

0 Patents (Medical) associated with PNMT

1,533

Literatures (Medical) associated with PNMT

01 Oct 2024·Cancer

Role of epigenetic regulation on catecholamine synthesis in pheochromocytoma and paraganglioma

Article

Author: Halperin, Reut ; Kaplinsky, Anna ; Shlomai, Gadi ; Tirosh, Amit

AbstractIntroductionPheochromocytomas and paragangliomas (PPGLs) typically secrete catecholamines and their metabolites (metanephrines [MN] and normetanephrine [NMN]). Catecholamines are synthesized by several enzymes: phenylalanine hydroxylase (encoded by PAH), tyrosine hydroxylase (TH), aromatic L‐amino acid decarboxylase (DDC), dopamine β‐hydroxylase (DBH), and phenylethanolamine N‐methyltransferase (PNMT). MN/NMN secretion varies between anatomical and molecular subgroups. The aim of this study was to assess the correlation between DNA methylation of catecholamine synthesis genes and MN/NMN secretion.MethodsGene promoter methylation of PAH, TH, AADC, DBH, and PNMT were extracted and calculated based on publicly available data. Comparisons and correlation analysis were performed between MN ± NMN (MN/NMN), NMN only, and neither/unknown secretion patterns. Methylation levels and MN/NMN patterns were compared by three genetic alteration subgroups: pseudohypoxia (PH), kinase signaling (KS), and others.ResultsA total of 178 cases were included. Methylation of PAH CpGs negatively correlated with probability for MN/NMN secretion (p < .05 for all CpGs) and positively with NMN‐only secretion. NMN‐only secreting tumors had significantly higher promoter methylation of PAH, DBH, and PNMT compared with MN/NMN‐secreting tumors. MN/NMN‐secreting PPGLs had mainly KS alterations (52.1%), whereas NMN‐only PPGLs had PH alterations (41.9%). PPGLs in the PH versus KS group had gene promoter hypermethylation of PAH (p = .002), DBH (p = .02), and PNMT (p = .003).ConclusionsPromoter methylation of genes encoding catecholamine synthesis enzymes is strongly and inversely correlated with MN/NMN patterns in PPGLs. KS and PH‐related tumors have distinct methylation patterns. These results imply that methylation is a key regulatory mechanism of catecholamine synthesis in PPGLs.

01 Jul 2024·Microcirculation

Role of Phenylethanolamine‐N‐methyltransferase on Nicotine‐Induced Vasodilation in Rat Cerebral Arteries

Article

Author: Chang, Hsi-Hsien ; Yang, Stephen Shei-Dei ; Chang, Shang-Jen ; Li, Ming-Wei

ABSTRACTObjectiveThe sympathetic–parasympathetic (or axo–axonal) interaction mechanism mediated that neurogenic relaxation, which was dependent on norepinephrine (NE) releases from sympathetic nerve terminal and acts on β2‐adrenoceptor of parasympathetic nerve terminal, has been reported. As NE is a weak β2‐adrenoceptor agonist, there is a possibility that synaptic NE is converted to epinephrine by phenylethanolamine‐N‐methyltransferase (PNMT) and then acts on the β2‐adrenoceptors to induce neurogenic vasodilation.MethodsBlood vessel myography technique was used to measure relaxation and contraction responses of isolated basilar arterial rings of rats.ResultsNicotine‐induced relaxation was sensitive to propranolol, guanethidine (an adrenergic neuronal blocker), and Nω‐nitro‐l‐arginine. Nicotine‐ and exogenous NE‐induced vasorelaxation was partially inhibited by LY‐78335 (a PNMT inhibitor), and transmural nerve stimulation depolarized the nitrergic nerve terminal directly and was not inhibited by LY‐78335; it then induced the release of nitric oxide (NO). Epinephrine‐induced vasorelaxation was not affected by LY‐78335. However, these vasorelaxations were completely inhibited by atenolol (a β1‐adrenoceptor antagonist) combined with ICI‐118,551 (a β2‐adrenoceptor antagonist).ConclusionsThese results suggest that NE may be methylated by PNMT to form epinephrine and cause the release of NO and vasodilation. These results provide further evidence supporting the physiological significance of the axo–axonal interaction mechanism in regulating brainstem vascular tone.

21 Jun 2024·ACS Synthetic Biology

Establishing an Artificial Pathway for the Biosynthesis of Octopamine and Synephrine

Article

Author: Cheng, Shasha ; Wang, Xin ; Li, Hui ; Feng, Jiao ; Jin, Runyuan ; Chen, Kequan

In this study, we designed an artificial pathway composed of tyramine β-hydroxylase (TBH) and phenylethanolamine N-methyltransferase (PNMT) for the biosynthesis of both octopamine and synephrine. As most TBH and PNMT originate from eukaryotic animals and plants, the heterologous expression and identification of functional TBH and PNMT are critical for establishing the pathway in mode microorganisms like Escherichia coli. Here, three TBHs were evaluated, and only TBH from Drosophila melanogaster was successfully expressed in the soluble form in E. coli. Its expression was promoted by evaluating the effects of different expression strategies. The specific enzyme activity of TBH was optimized up to 229.50 U·g^-1, and the first step in the biosynthetic pathway was successfully established and converted tyramine to synthesize 0.10 g/L of octopamine. Furthermore, the second step to produce synephrine from octopamine was developed by screening PNMT, enhancing enzyme activity, and optimizing reaction conditions, with a maximum synephrine production of 2.02 g/L. Finally, based on the optimization of the reaction conditions for each individual reaction, the one-pot cascade reaction for synthesizing synephrine from tyramine was constructed by combining the TBH and PNMT. The synthetic synephrine reached 30.05 mg/L with tyramine as substrate in the two-step enzyme cascade system. With further optimization and amplification, the titers of octopamine and synephrine were increased to 0.45 and 0.20 g/L, respectively, with tyramine as substrate. This work was the first achievement of the biosynthesis of octopamine and synephrine to date.

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