Reaction participants Show >> << Hide
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,204 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline S-inosyl-L-homocysteine Identifier CHEBI:57985 Charge 0 Formula C14H19N5O6S InChIKeyhelp_outline VNPWVMVYUSNFAW-WFMPWKQPSA-N SMILEShelp_outline [NH3+][C@@H](CCSC[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1cnc2c(O)ncnc12)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline inosine Identifier CHEBI:17596 (Beilstein: 624889; CAS: 58-63-9) help_outline Charge 0 Formula C10H12N4O5 InChIKeyhelp_outline UGQMRVRMYYASKQ-KQYNXXCUSA-N SMILEShelp_outline OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)n1cnc2c(O)ncnc12 2D coordinates Mol file for the small molecule Search links Involved in 20 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline L-homocysteine Identifier CHEBI:58199 Charge 0 Formula C4H9NO2S InChIKeyhelp_outline FFFHZYDWPBMWHY-VKHMYHEASA-N SMILEShelp_outline [NH3+][C@@H](CCS)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 20 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:59828 | RHEA:59829 | RHEA:59830 | RHEA:59831 | |
---|---|---|---|---|
Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
UniProtKB help_outline |
|
|||
EC numbers help_outline | ||||
MetaCyc help_outline |
Publications
-
S-Inosyl-L-Homocysteine Hydrolase, a Novel Enzyme Involved in S-Adenosyl-L-Methionine Recycling.
Miller D., Xu H., White R.H.
<h4>Unlabelled</h4>S-Adenosyl-L-homocysteine, the product of S-adenosyl-L-methionine (SAM) methyltransferases, is known to be a strong feedback inhibitor of these enzymes. A hydrolase specific for S-adenosyl-L-homocysteine produces L-homocysteine, which is remethylated to methionine and can be use ... >> More
<h4>Unlabelled</h4>S-Adenosyl-L-homocysteine, the product of S-adenosyl-L-methionine (SAM) methyltransferases, is known to be a strong feedback inhibitor of these enzymes. A hydrolase specific for S-adenosyl-L-homocysteine produces L-homocysteine, which is remethylated to methionine and can be used to regenerate SAM. Here, we show that the annotated S-adenosyl-L-homocysteine hydrolase in Methanocaldococcus jannaschii is specific for the hydrolysis and synthesis of S-inosyl-L-homocysteine, not S-adenosyl-L-homocysteine. This is the first report of an enzyme specific for S-inosyl-L-homocysteine. As with S-adenosyl-L-homocysteine hydrolase, which shares greater than 45% sequence identity with the M. jannaschii homologue, the M. jannaschii enzyme was found to copurify with bound NAD(+) and has Km values of 0.64 ± 0.4 mM, 0.0054 ± 0.006 mM, and 0.22 ± 0.11 mM for inosine, L-homocysteine, and S-inosyl-L-homocysteine, respectively. No enzymatic activity was detected with S-adenosyl-L-homocysteine as the substrate in either the synthesis or hydrolysis direction. These results prompted us to redesignate the M. jannaschii enzyme an S-inosyl-L-homocysteine hydrolase (SIHH). Identification of SIHH demonstrates a modified pathway in this methanogen for the regeneration of SAM from S-adenosyl-L-homocysteine that uses the deamination of S-adenosyl-L-homocysteine to form S-inosyl-L-homocysteine.<h4>Importance</h4>In strictly anaerobic methanogenic archaea, such as Methanocaldococcus jannaschii, canonical metabolic pathways are often not present, and instead, unique pathways that are deeply rooted on the phylogenetic tree are utilized by the organisms. Here, we discuss the recycling pathway for S-adenosyl-L-homocysteine, produced from S-adenosyl-L-methionine (SAM)-dependent methylation reactions, which uses a hydrolase specific for S-inosyl-L-homocysteine, an uncommon metabolite. Identification of the pathways and the enzymes involved in the unique pathways in the methanogens will provide insight into the biochemical reactions that were occurring when life originated. << Less