nicotinamide N-methyltransferase | |||||||||
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Identifiers | |||||||||
EC no. | 2.1.1.1 | ||||||||
CAS no. | 9029-74-7 | ||||||||
Databases | |||||||||
IntEnz | IntEnz view | ||||||||
BRENDA | BRENDA entry | ||||||||
ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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In enzymology, a nicotinamide N-methyltransferase (NNMT) (EC 2.1.1.1) is an enzyme that catalyzes the chemical reaction
Thus, the two substrates of this enzyme are S-adenosyl methionine and nicotinamide, whereas its two products are S-adenosylhomocysteine and 1-methylnicotinamide.
This enzyme belongs to the family of transferases, specifically those transferring one-carbon group methyltransferases. The systematic name of this enzyme class is S-adenosyl-L-methionine:nicotinamide N-methyltransferase. This enzyme is also called nicotinamide methyltransferase.
This enzyme participates in nicotinate and nicotinamide metabolism.
NNMT affects a biochemical mechanism known as a futile cycle, which plays a role in metabolic regulation. NNMT is found in human fat cells and the liver. NNMT processes vitamin B3 and has been linked with certain types of cancer. Silencing the gene that codes for NNMT reduces its presence and increases the presence of sugar transporter GLUT4. [1]
Mice that produced large amounts of GLUT4 were insulin sensitive and protected against diabetes, while mice with no GLUT4 were insulin resistant and at risk. High levels of NNMT are often found in the fat cells of animals that are insulin resistant. When the researchers silenced the NNMT gene in mice on high-fat diets, the mice gained less weight than those in whom the NNMT gene was functioning normally. (The mice did not change their eating or exercise habits). [1]
Antisense oligonucleotide (ASO) technology can be used to silence the expression of the NNMT gene only in fat and liver cells. ASOs are short strings of DNA that can be designed to prevent the synthesis of specific proteins. ASOs have been approved for use by the U.S. Food and Drug Administration for the treatment of conditions with other genetic causes—such as elevated cholesterol and hyperlipidemia. [1]
As of late 2007, two structures have been solved for this class of enzymes, with PDB accession codes 2I62 and 2IIP.
S-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throughout the body, most SAM is produced and consumed in the liver. More than 40 methyl transfers from SAM are known, to various substrates such as nucleic acids, proteins, lipids and secondary metabolites. It is made from adenosine triphosphate (ATP) and methionine by methionine adenosyltransferase. SAM was first discovered by Giulio Cantoni in 1952.
Thiopurine methyltransferase or thiopurine S-methyltransferase (TPMT) is an enzyme that in humans is encoded by the TPMT gene. A pseudogene for this locus is located on chromosome 18q.
Glucose transporter type 4 (GLUT4), also known as solute carrier family 2, facilitated glucose transporter member 4, is a protein encoded, in humans, by the SLC2A4 gene. GLUT4 is the insulin-regulated glucose transporter found primarily in adipose tissues and striated muscle. The first evidence for this distinct glucose transport protein was provided by David James in 1988. The gene that encodes GLUT4 was cloned and mapped in 1989.
Methyltransferases are a large group of enzymes that all methylate their substrates but can be split into several subclasses based on their structural features. The most common class of methyltransferases is class I, all of which contain a Rossmann fold for binding S-Adenosyl methionine (SAM). Class II methyltransferases contain a SET domain, which are exemplified by SET domain histone methyltransferases, and class III methyltransferases, which are membrane associated. Methyltransferases can also be grouped as different types utilizing different substrates in methyl transfer reactions. These types include protein methyltransferases, DNA/RNA methyltransferases, natural product methyltransferases, and non-SAM dependent methyltransferases. SAM is the classical methyl donor for methyltransferases, however, examples of other methyl donors are seen in nature. The general mechanism for methyl transfer is a SN2-like nucleophilic attack where the methionine sulfur serves as the leaving group and the methyl group attached to it acts as the electrophile that transfers the methyl group to the enzyme substrate. SAM is converted to S-Adenosyl homocysteine (SAH) during this process. The breaking of the SAM-methyl bond and the formation of the substrate-methyl bond happen nearly simultaneously. These enzymatic reactions are found in many pathways and are implicated in genetic diseases, cancer, and metabolic diseases. Another type of methyl transfer is the radical S-Adenosyl methionine (SAM) which is the methylation of unactivated carbon atoms in primary metabolites, proteins, lipids, and RNA.
N-Acetylserotonin O-methyltransferase, also known as ASMT, is an enzyme which catalyzes the final reaction in melatonin biosynthesis: converting Normelatonin to melatonin. This reaction is embedded in the more general tryptophan metabolism pathway. The enzyme also catalyzes a second reaction in tryptophan metabolism: the conversion of 5-hydroxy-indoleacetate to 5-methoxy-indoleacetate. The other enzyme which catalyzes this reaction is n-acetylserotonin-o-methyltransferase-like-protein.
Hypermethioninemia is an excess of the amino acid methionine, in the blood. This condition can occur when methionine is not broken down properly in the body.
Histamine N-methyltransferase (HNMT) is a protein encoded by the HNMT gene in humans. It belongs to the methyltransferases superfamily of enzymes and plays a role in the inactivation of histamine, a biomolecule that is involved in various physiological processes. Methyltransferases are present in every life form including archaeans, with 230 families of methyltransferases found across species.
Amine N-methyltransferase, also called indolethylamine N-methyltransferase, and thioether S-methyltransferase, is an enzyme that is ubiquitously present in non-neural tissues and catalyzes the N-methylation of tryptamine and structurally related compounds. More recently, it was discovered that this enzyme can also catalyze the methylation of thioether and selenoether compounds, although the physiological significance of this biotransformation is not yet known.
In enzymology, a caffeate O-methyltransferase is an enzyme that catalyzes the chemical reaction
In enzymology, a carnosine N-methyltransferase is an enzyme that catalyzes the chemical reaction
Guanidinoacetate N-methyltransferase is an enzyme that catalyzes the chemical reaction and is encoded by gene GAMT located on chromosome 19p13.3.
In enzymology, an indolepyruvate C-methyltransferase is an enzyme that catalyzes the chemical reaction
In enzymology, a nicotinate N-methyltransferase is an enzyme that catalyzes the chemical reaction
Phosphatidylethanolamine N-methyltransferase is a transferase enzyme which converts phosphatidylethanolamine (PE) to phosphatidylcholine (PC) in the liver. In humans it is encoded by the PEMT gene within the Smith–Magenis syndrome region on chromosome 17.
In enzymology, a phosphatidyl-N-methylethanolamine N-methyltransferase is an enzyme that catalyzes the chemical reaction
In enzymology, a precorrin-4 C11-methyltransferase is an enzyme that catalyzes the chemical reaction
In enzymology, a thiol S-methyltransferase is an enzyme that catalyzes the chemical reaction
In enzymology, a tRNA (guanine-N2-)-methyltransferase (EC 2.1.1.32) is an enzyme that catalyzes the chemical reaction
Nicotinamide N-methyltransferase (NNMT) is an enzyme that in humans is encoded by the NNMT gene. NNMT catalyzes the methylation of nicotinamide and similar compounds using the methyl donor S-adenosyl methionine (SAM-e) to produce S-adenosyl-L-homocysteine (SAH) and 1-methylnicotinamide.
1-Methylnicotinamide (trigonellamide) is a prototypic organic cation. 1-Methylnicotinamide is the methylated amide of Nicotinamide (niacinamide, vitamin B3).