GNMT

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Protein-coding gene in the species Homo sapiens

title: "GNMT" type: doc version: 1 created: 2026-02-28 author: "Wikipedia contributors" status: active scope: public description: "Protein-coding gene in the species Homo sapiens" topic_path: "uncategorized" source: "https://en.wikipedia.org/wiki/GNMT" license: "CC BY-SA 4.0" wikipedia_page_id: 0 wikipedia_revision_id: 0

::summary Protein-coding gene in the species Homo sapiens ::

Glycine N-methyltransferase is an enzyme that in humans is encoded by the GNMT gene.

Discovery

The enzyme was first described by Blumenstein and Williams (1960) in guinea pig liver. However, this enzyme was not purified until 1972 in the rabbit liver by Kerr. In 1984, Cook and Wagner demonstrated that a liver cytosolic folate binding protein is identical to GNMT. The human GMNT gene was cloned in 2000 by Chen and coworkers.

Tissue distribution

GNMT is an abundant enzyme in liver cytosol and consists of 0.9% to 3% of the soluble protein present in liver. In addition to liver, GNMT activity has been found in a number of other tissues including pancreas and kidney. GNMT is most abundant in the peri-portal region of the liver and exocrine tissue of the pancreas. The GNMT proteins located in tissues that are actively in secretion, such as the proximal kidney tubules, the submaxillary glands and the intestinal mucosa. GNMT is also expressed in various neurons presented in the cerebral cortex, hippocampus, substantia nigra and cerebellum. The presence of GNMT in these cells suggests that this enzyme may play a role in secretion.

Structure

The properties of GNMT protein from rabbits, rats and humans, either purified from liver/pancreas, or expressed in Escherichia coli, have been well characterized. All GNMTs have very similar molecular and kinetic properties. Comparison of the cDNA and protein sequences of human, rabbit, pig and rat GNMTs shows similarities of over 84% at the nucleotide level and about 90% at the amino acid level. All GNMTs are 130 kDa tetramers consisting of four identical subunits, each having a Mr of 32 kDa. The structure of recombinant rat, mouse and human GNMTs have been solved. The four nearly spherical subunits are arranged to form a flat and square tetramer with a large hole in the center. The active sites are located in the near center of each subunit.

Function

Glycine N-methyltransferase catalyzes the synthesis of N-methylglycine (sarcosine) from glycine using S-adenosylmethionine (SAM) (AdoMet) as the methyl donor. GNMT acts as an enzyme to regulate the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH) (AdoHcy) and participates in the detoxification pathway in liver cells. GNMT competes with tRNA methyltransferases for SAM and the product, S-adenosylhomocysteine (SAH), is a potent inhibitor of tRNA methyltransferases and a relatively weak inhibitor of GNMT. GNMT regulates the relative levels of SAM and SAH. Since SAM is the methyl donor for almost all cellular methylation reactions. GNMT is therefore likely to regulate cellular methylation capacity. An endogenous ligand of GNMT, 5-methyltetrahydropteroylpentaglutamate (5-CH3-H4PteGIu5) is a powerful inhibitor of this enzyme. Thus, GNMT has been proposed to link the de novo synthesis of methyl groups to the ratio of SAM to SAH, which in turn serves as a bridge between methionine and one-carbon metabolism.

In addition to the methyltransferase activity, the 4S polycyclic aromatic hydrocarbon (PAH)-binding protein and GNMT are one and the same protein. The catalytic site resembles a molecular basket, unlike most other SAM-dependent methyltransferases, which therefore suggests that GNMT may be capable of capturing unidentified chemicals as a part of a detoxification process. Therefore, GNMT has been proposed to be a protein with diverse functionality.

Clinical significance

GNMT has been shown to detoxify some environmental carcinogens such as polyaromatic hydrocarbons and aflatoxin.

There is mounting evidence that supports the involvement of GNMT deficiency in liver carcinogenesis.

Inducer

The glycoside natural product 1,2,3,4,6-penta-O-galloyl-β-d-glucopyranoside (PGG) isolated from Paeonia lactiflora, an Asian flower plant, induces GNMT mRNA and protein expression in Huh7 human hepatoma cells.

References

References

  1. "Entrez Gene: GNMT glycine N-methyltransferase".
  2. (2009). "Inherited disorders in the conversion of methionine to homocysteine". Journal of Inherited Metabolic Disease.
  3. (August 1997). "Glycine N-methyltransferase is an example of functional diversity. Role as a polycyclic aromatic hydrocarbon-binding receptor". The Journal of Biological Chemistry.
  4. (September 1960). "The enzymic N-methylation of glycine". Biochemical and Biophysical Research Communications.
  5. (March 1998). "Characterization of glycine-N-methyltransferase-gene expression in human hepatocellular carcinoma". International Journal of Cancer.
  6. (May 2000). "Genomic structure, expression, and chromosomal localization of the human glycine N-methyltransferase gene". Genomics.
  7. (1984). "Glycine N-methyltransferase is a folate binding protein of rat liver cytosol". Proceedings of the National Academy of Sciences of the United States of America.
  8. (1996). "Crystal structure of glycine N-methyltransferase from rat liver". Biochemistry.
  9. (1973). "Purification and characterization of glycine N-methyltransferase". The Journal of Biological Chemistry.
  10. (May 2016). "Identification of 1,2,3,4,6-Penta-O-galloyl-β-d-glucopyranoside as a Glycine N-Methyltransferase Enhancer by High-Throughput Screening of Natural Products Inhibits Hepatocellular Carcinoma". International Journal of Molecular Sciences.
  11. (1972). "Advances in Enzymology and Related Areas of Molecular Biology".
  12. (2009). "Glycine N-methyltransferase and regulation of S-adenosylmethionine levels". The Journal of Biological Chemistry.
  13. (2005). "DNA methylation, genomic silencing, and links to nutrition and cancer". Nutrition Reviews.
  14. (1982). "Purification and properties of glycine N-methyltransferase from rat liver". The Journal of Biological Chemistry.
  15. (1993). "Mammalian glycine N-methyltransferases. Comparative kinetic and structural properties of the enzymes from human, rat, rabbit and pig livers". Comparative Biochemistry and Physiology. B, Comparative Biochemistry.
  16. (2004). "Glycine N-methyltransferases: a comparison of the crystal structures and kinetic properties of recombinant human, mouse and rat enzymes". Proteins.
  17. (1994). "Rat liver cytosolic 4 S polycyclic aromatic hydrocarbon-binding protein is glycine N-methyltransferase". The Journal of Biological Chemistry.
  18. (August 2012). "Characterization of the neuropsychological phenotype of glycine N-methyltransferase-/- mice and evaluation of its responses to clozapine and sarcosine treatments". European Neuropsychopharmacology.
  19. (January 2013). "The multi-functional roles of GNMT in toxicology and cancer". Toxicology and Applied Pharmacology.
  20. (1992). "Purification and properties of pancreatic glycine N-methyltransferase". The Journal of Biological Chemistry.
  21. (1994). "Tissue distribution of glycine N-methyltransferase, a major folate-binding protein of liver". Proceedings of the National Academy of Sciences of the United States of America.
  22. (1985). "Inhibition of glycine N-methyltransferase activity by folate derivatives: implications for regulation of methyl group metabolism". Biochemical and Biophysical Research Communications.

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