Table 1.
Key enzymes in methionine metabolic pathway.
| Gene symbol | Name | Chr | Start | Stop | Nature | Function |
|---|---|---|---|---|---|---|
| Transferase | ||||||
| BHMT | Betaine-homocysteine S-methyltransferase | 5 | 79,111,781 | 79,132,290 | Methionine regeneration | Conversion of betaine and homocysteine to dimethylglycine and methionine, respectively |
| CARM1 | Coactivator-associated arginine methyltransferase 1 | 19 | 10,871,577 | 10,923,078 | SAM consuming | Methylation of guanidino nitrogens of arginyl residues of proteins—acts specifically on histones and chromatin |
| COMT | Catechol-O-methyltransferase | 22 | 19,941,740 | 19,969,975 | SAM consuming | Transfers a methyl group from SAM to catecholamines, including the neurotransmitters dopamine, epinephrine, and norepinephrine |
| DNMT1 | DNA methyltransferase 1 | 19 | 10,133,344 | 10,195,135 | SAM consuming | Transfers methyl groups to cytosine nucleotides of genomic DNA—maintain methylation patterns |
| DNMT3A | DNA methyltransferase 3 alpha | 2 | 25,232,961 | 25,342,590 | SAM consuming | CpG methylation—preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1—repress transcription through the recruitment of HDAC activity |
| DNMT3B | DNA methyltransferase 3 beta | 20 | 32,762,385 | 32,809,356 | SAM consuming | Modulates dimethylation of promoter histone H3 at H3K4 and H3K9—function as a transcriptional corepressor by associating with ZHX1 |
| DOT1L | DOT1-like histone lysine methyltransferase | 19 | 2,163,963 | 2,232,578 | SAM consuming | Methylates lysine-79 of histone H3. It is inactive against free core histones, but shows significant histone methyltransferase activity against nucleosomes |
| GAMT | Guanidinoacetate N-methyltransferase | 19 | 1,397,026 | 1,401,570 | SAM consuming | Converts guanidoacetate to creatine, using S-adenosylmethionine as the methyl donor |
| GNMT | Glycine N-methyltransferase | 6 | 42,960,754 | 42,963,880 | SAM consuming | Conversion of S-adenosyl-l-methionine (along with glycine) to S-adenosyl-l-homocysteine and sarcosine |
| HNMT | Histamine N-methyltransferase | 2 | 137,964,068 | 138,016,364 | SAM consuming | Histamine is metabolized by two major pathways: N(tau)-methylation via histamine N-methyltransferase and oxidative deamination via diamine oxidase |
| KMT5A | Lysine methyltransferase 5A | 12 | 123,383,778 | 123,409,357 | SAM consuming | Protein-lysine N-methyltransferase that can monomethylate Lys-20 of histone H4 to effect transcriptional repression of some genes |
| MAT-1A/2A/2B | Methionine adenosyltransferases | 10,2,5 | 80,271,820 | 80,290,003 | SAM generating | Catalyzes the transfer of the adenosyl moiety of ATP to methionine to form SAM and tripolyphosphate—SAM is the source of methyl groups for most biological methylations |
| MRM2/FTSJ2 | Mitochondrial rRNA methyltransferase 2 | 7 | 2,234,291 | 2,242,198 | SAM consuming | SAM-binding protein family—nucleolar protein and it may be involved in the processing and modification of rRNA |
| MTFMT | Mitochondrial methionyl-tRNA formyltransferase | 15 | 65,001,512 | 65,029,639 | SAM consuming | Formylates methionyl-tRNA in mitochondria. A single tRNA(Met) gene gives rise to both an initiator and an elongator species via an unknown mechanism |
| MTR | 5-Methyltetrahydrofolate-homocysteine methyltransferase | 1 | 236,794,304 | 236,903,981 | Methionine regeneration | Catalyzes the transfer of a methyl group from methyl-cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine—remethylates the cofactor using methyltetrahydrofolate |
| NNMT | Nicotinamide N-methyltransferase | 11 | 114,295,813 | 114,312,516 | SAM consuming | Catalyzes the N-methylation of nicotinamide and other pyridines to form pyridinium ions |
| PCMT1 | Protein-l-isoaspartate (d-aspartate) O-methyltransferase | 6 | 149,749,695 | 149,811,421 | SAM consuming | Protein carboxyl methyltransferase—converts d-aspartyl and l-isoaspartyl residues resulting from spontaneous deamidation back to the normal l-aspartyl form |
| PEMT | Phosphatidylethanolamine N-methyltransferase | 17 | 17,505,561 | 17,591,703 | SAM consuming | Converts phosphatidylethanolamine to phosphatidylcholine by sequential methylation in the liver by utilizing SAM |
| PNMT | Phenylethanolamine N-methyltransferase | 17 | 39,667,981 | 39,670,475 | SAM consuming | Catalyzes the last step of the catecholamine biosynthesis pathway, which methylates norepinephrine to form epinephrine (adrenaline) |
| PRMT1 | Protein arginine methyltransferase 1 | 19 | 49,676,166 | 49,688,450 | SAM consuming | PRMTs methylate arginine residues on histones and other proteins by transferring methyl groups from SAM to terminal guanidino nitrogen atoms |
| PRMT-2/-3/-5/-6/-7/-9 | Protein arginine methyltransferases | 21,11,14,1,16, and 4 | SAM consuming | PRMTs methylate arginine residues by transferring methyl groups from SAM | ||
| RNMT | RNA guanine-7 methyltransferase | 18 | 13,726,647 | 13,764,556 | SAM consuming | mRNA-capping methyltransferase—methylates the N7 position of the added guanosine to the 5-cap structure of mRNAs—binds RNA containing 5-terminal GpppC |
| SETD7 | SET domain containing lysine methyltransferase 7 | 4 | 139,495,934 | 139,556,769 | SAM consuming | SET domain containing lysine methyltransferase 7-lysine methyltransferases—transfers methyl groups from SAM to the lysine residues on histones, particularly histones H3 and H4 |
| SETDB1 | SET domain bifurcated 1 | 1 | 150,926,246 | 150,964,744 | SAM consuming | Trimethylates Lys-9 of histone H3—epigenetic transcriptional repression by recruiting proteins to methylated histones |
| SHMT1 | Serine hydroxymethyltransferase 1 | 17 | 18,327,860 | 18,363,563 | Methionine regeneration | Serine hydroxymethyltransferase 1—interconversion of serine and glycine—this reaction provides one-carbon units for synthesis of methionine, thymidylate, and purines in the cytoplasm |
| SMYD2 | SET and MYND domain containing 2 | 1 | 214,281,101 | 214,337,134 | SAM consuming | Catalyze the transfer of methyl groups from S-adenosylmethionine (SAM) to the lysine residues on histones, particularly histones H3 and H4 |
| SUV39H1 | Suppressor of variegation 3–9 homolog 1 | X | 48,695,554 | 48,709,016 | SAM consuming | N-terminal chromodomain and a C-terminal SET domain—catalyze the transfer of methyl groups from S-adenosylmethionine (SAM) to the lysine residues on histones, particularly histones H3 and H4 |
| Reductase | ||||||
| MSRB2 | Methionine sulfoxide reductase B2 | 10 | 23,095,498 | 23,122,013 | Methionine regeneration | Reduces methionine sulfoxide back to methionine—methionine oxidation due to oxidative stress decreases the intracellular ROS |
| MSRB3 | Methionine sulfoxide reductase B3 | 12 | 65,278,643 | 65,466,907 | Methionine regeneration | Catalyzes the reduction of free and protein-bound methionine sulfoxide to methionine |
| MTHFR | Methylenetetrahydrofolate reductase | 1 | 11,785,730 | 11,806,103 | Methionine regeneration | Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine |
| MTRR | 5-Methyltetrahydrofolate-homocysteine methyltransferase reductase | 5 | 7,869,104 | 7,901,124 | Methionine regeneration | Electron transferases involved in the reductive regeneration of cob(I)alamin (vitamin B12) cofactor required for the maintenance of methionine synthase in a functional state |
| Synthase | ||||||
| CBS | Cystathionine-beta-synthase | 21 | 43,053,190 | 43,076,868 | SAH consuming | Catalyze the conversion of homocysteine to cystathionine |
| SMS | Spermine synthase | X | 21,940,573 | 21,994,837 | Decarboxy-SAM consuming | spermidine/spermin synthase family-Catalyzes the production of spermine from spermidine and decarboxylated S-adenosylmethionine (dcSAM) |
| SRM | Spermidine synthase | 1 | 11,054,592 | 11,060,053 | Decarboxy-SAM consuming | |
| Decarboxylase | ||||||
| AMD1 | Adenosylmethionine decarboxylase 1 | 6 | 110,814,621 | 110,895,713 | SAM consuming | Important intermediate enzyme in polyamine biosynthesis |
| Synthetase | ||||||
| MARS | Methionyl-tRNA synthetase | 12 | 57,487,953 | 57,516,655 | Methionine consuming | Aminoacyl-tRNA synthetases—play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids |
| Phosphorylase | ||||||
| MTAP | Methylthioadenosine phosphorylase | 9 | 21,802,636 | 21,865,971 | SAM consuming | Salvage of both adenine and methionine—catalyzes the reversible phosphorylation of MTA to adenine and 5-MTR-1-P. Responsible for the first step in the methionine salvage pathway after MTA has been generated from S-adenosylmethionine |
| Miscellaneous | ||||||
| AHCY | Adenosylhomocysteinase | 20 | 34,235,012 | 34,311,976 | SAH generating | Catalyzes the reversible hydrolysis of SAH to adenosine and L-homocysteine—regulates intracellular SAH concentration |
| CTH | Cystathionine gamma-lyase | 1 | 70,411,218 | 70,441,949 | Methionine consuming | Encodes a cytoplasmic enzyme in the trans-sulfuration pathway that converts cystathione derived from methionine into cysteine. Glutathione synthesis in the liver is dependent upon the availability of cysteine |
| EZH2 | Enhancer of zeste 2 polycomb repressive complex 2 subunit | 7 | 148,807,372 | 148,884,662 | SAM consuming | Polycomb-group (PcG) family—multimeric protein complexes involved in maintaining the transcriptional repressive state of genes over successive cell generations by methylation of histones |