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MetaCyc Enzyme: phenylethanolamine N-methyltransferase

Gene: PNMT Accession Number: HS06868 (MetaCyc)

Synonyms: PENT, noradrenaline N-methyltransferase, noradrenalin N-methyltransferase, norepinephrine methyltransferase, norepinephrine N-methyltransferase, phenethanolamine methyltransferase, phenethanolamine N-methyltransferase

Species: Homo sapiens

Summary:
phenylethanolamine N-methyltransferase (PNMT) is the final enzyme in the synthesis of (R)-adrenaline (aka epinephrine) in small groups of brainstem neurons, and in the adrenal medulla. The enzyme was first purified from Macaca mulatta adrenal gland tissue.

The cDNA has been isolated and sequenced, and the PNMT gene was assigned to chromosome 17 [Kaneda et al., 1988, Hoehe et al., 1992]. The gene has been cloned and sequenced [Baetge et al., 1988]. The enzyme has been purified and crystallized, and the crystal structure determined [Begun et al., 2002].

When expressed in transgenic mice, the protein was detected in nuclei of adrenal medullary cells and cells of the inner nuclear cell layer of the retina, prominent sites of adrenaline synthesis [Baetge et al., 1988].

Purified enzyme was shown to also possess a beta-carboline 2N-methyltransferase activity that converts beta-carbolines, such as norharman and harman, into 2N-methylated beta-carbolinium cations, which are structural and functional analogs of the Parkinsonian-inducing toxin 1-methyl-4-phenylpyridinium cation (MPP+) [Gearhart et al., 2002].

The PNMT gene has been associated with multiple sclerosis [Mann et al., 2002].

Map Position: [39,822,470 -> 39,824,488]

Molecular Weight of Polypeptide: 30.855 kD (from nucleotide sequence), 30 kD (experimental)

Unification Links: ArrayExpress:P11086 , Ensembl:ENSG00000141744 , Entrez-gene:5409 , GeneCards:PNMT , OMIM:171190 , PhosphoSite:P11086 , PhylomeDB:P11086 , Pride:P11086 , Protein Model Portal:P11086 , RefSeq:NM_002686 , RefSeq:NP_002677 , SMR:P11086 , String:9606.ENSP00000269582 , UCSC Human Genome:NM_002686 , UniGene:1892 , UniProt:P11086

Relationship Links: Entrez-Nucleotide:PART-OF:BC037246 , Entrez-Nucleotide:PART-OF:J03280 , Entrez-Nucleotide:PART-OF:J03727 , Entrez-Nucleotide:PART-OF:X52730 , InterPro:IN-FAMILY:IPR000940 , InterPro:IN-FAMILY:IPR025820 , InterPro:IN-FAMILY:IPR029063 , Panther:IN-FAMILY:PTHR10867 , PDB:Structure:1HNN , PDB:Structure:1N7I , PDB:Structure:1N7J , PDB:Structure:1YZ3 , PDB:Structure:2AN3 , PDB:Structure:2AN4 , PDB:Structure:2AN5 , PDB:Structure:2G8N , PDB:Structure:2G70 , PDB:Structure:2G71 , PDB:Structure:2G72 , PDB:Structure:2OBF , PDB:Structure:2ONY , PDB:Structure:2ONZ , PDB:Structure:2OPB , PDB:Structure:3HCA , PDB:Structure:3HCB , PDB:Structure:3HCC , PDB:Structure:3HCD , PDB:Structure:3HCE , PDB:Structure:3HCF , PDB:Structure:3KPJ , PDB:Structure:3KPU , PDB:Structure:3KPV , PDB:Structure:3KPW , PDB:Structure:3KPY , PDB:Structure:3KQM , PDB:Structure:3KQO , PDB:Structure:3KQP , PDB:Structure:3KQQ , PDB:Structure:3KQS , PDB:Structure:3KQT , PDB:Structure:3KQV , PDB:Structure:3KQW , PDB:Structure:3KQY , PDB:Structure:3KR0 , PDB:Structure:3KR1 , PDB:Structure:3KR2 , PDB:Structure:4DM3 , Pfam:IN-FAMILY:PF01234 , Prosite:IN-FAMILY:PS01100 , Prosite:IN-FAMILY:PS51681

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Credits:
Revised 22-Jun-2009 by Caspi R , SRI International


Enzymatic reaction of: phenylethanolamine N-methyltransferase

EC Number: 2.1.1.28

phenylethanolamine + S-adenosyl-L-methionine <=> S-adenosyl-L-homocysteine + N-methylphenylethanolamine + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.


Enzymatic reaction of: noradrenaline N-methyltransferase (phenylethanolamine N-methyltransferase)

EC Number: 2.1.1.28

S-adenosyl-L-methionine + (R)-noradrenaline <=> S-adenosyl-L-homocysteine + (R)-adrenaline + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

In Pathways: noradrenaline and adrenaline degradation , catecholamine biosynthesis

Inhibitors (Unknown Mechanism): Mg2+ [Connett & Kirshner, 1970] , Fe2+ [Connett & Kirshner, 1970] , Cu2+ [Connett & Kirshner, 1970]

pH(opt): 7.9 [Comment 1, Connett & Kirshner, 1970]

Exons/Introns:

Schematic showing introns, exons and/or isoforms of PNMT


References

Axelrod, 1962: Axelrod J (1962). "Purification and properties of phenylethanolamine-N-methyl transferase." J Biol Chem 237;1657-60. PMID: 13863458

Baetge et al., 1988: Baetge EE, Behringer RR, Messing A, Brinster RL, Palmiter RD (1988). "Transgenic mice express the human phenylethanolamine N-methyltransferase gene in adrenal medulla and retina." Proc Natl Acad Sci U S A 85(10);3648-52. PMID: 2835776

Begun et al., 2002: Begun J, McLeish MJ, Caine JM, Palant E, Grunewald GL, Martin JL (2002). "Crystallization of PNMT, the adrenaline-synthesizing enzyme, is critically dependent on a high protein concentration." Acta Crystallogr D Biol Crystallogr 58(Pt 2);314-5. PMID: 11807261

Connett & Kirshner, 1970: Connett RJ, Kirshner N (1970). "Purification and properties of bovine phenylethanolamine N-methyltransferase." J Biol Chem 245(2);329-34. PMID: 5412063

Gearhart et al., 2002: Gearhart DA, Neafsey EJ, Collins MA (2002). "Phenylethanolamine N-methyltransferase has beta-carboline 2N-methyltransferase activity: hypothetical relevance to Parkinson's disease." Neurochem Int 40(7);611-20. PMID: 11900856

Hoehe et al., 1992: Hoehe MR, Plaetke R, Otterud B, Stauffer D, Holik J, Byerley WF, Baetge EE, Gershon ES, Lalouel JM, Leppert M (1992). "Genetic linkage of the human gene for phenylethanolamine N-methyltransferase (PNMT), the adrenaline-synthesizing enzyme, to DNA markers on chromosome 17q21-q22." Hum Mol Genet 1(3);175-8. PMID: 1303174

Kaneda et al., 1988: Kaneda N, Ichinose H, Kobayashi K, Oka K, Kishi F, Nakazawa A, Kurosawa Y, Fujita K, Nagatsu T (1988). "Molecular cloning of cDNA and chromosomal assignment of the gene for human phenylethanolamine N-methyltransferase, the enzyme for epinephrine biosynthesis." J Biol Chem 263(16);7672-7. PMID: 3372503

Mann et al., 2002: Mann MB, Wu S, Rostamkhani M, Tourtellotte W, MacMurray JP, Comings DE (2002). "Association between the phenylethanolamine N-methyltransferase gene and multiple sclerosis." J Neuroimmunol 124(1-2);101-5. PMID: 11958827


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 19.0 on Fri Mar 27, 2015, biocyc14.