| First Author | Castro C | Year | 2008 |
| Journal | Arch Biochem Biophys | Volume | 472 |
| Issue | 1 | Pages | 26-33 |
| PubMed ID | 18262489 | Mgi Jnum | J:135305 |
| Mgi Id | MGI:3793367 | Doi | 10.1016/j.abb.2008.01.017 |
| Citation | Castro C, et al. (2008) Liver betaine-homocysteine S-methyltransferase activity undergoes a redox switch at the active site zinc. Arch Biochem Biophys 472(1):26-33 |
| abstractText | Using a redox-inert methyl acceptor, we show that betaine-homocysteine S-methyltransferase (BHMT) requires a thiol reducing agent for activity. Short-term exposure of BHMT to reducing agent-free buffer inactivates the enzyme without causing any loss of its catalytic zinc. Activity can be completely restored by the re-addition of a thiol reducing agent. The catalytic zinc of BHMT is bound by three thiolates and one hydroxyl group. Thiol modification experiments indicate that a disulfide bond is formed between two of the three zinc-binding ligands when BHMT is inactive in a reducing agent-free buffer, and that this disulfide can be readily reduced with the concomitant restoration of activity by re-establishing reducing conditions. Long-term exposure of BHMT to reducing agent-free buffer results in the slow, irreversible loss of its catalytic Zn and a corresponding loss of activity. Experiments using the glutamate-cysteine ligase modifier subunit knockout mice Gclm(-/-), which are severely impaired in glutathione synthesis, show that BHMT activity is reduced about 75% in Gclm(-/-) compared to Gclm(+/+) mice. |
