論文 - 詳細
| RRC ID | 66172 |
|---|---|
| 著者 | Warnhoff K, Hercher TW, Mendel RR, Ruvkun G. |
| タイトル | Protein-bound molybdenum cofactor is bioavailable and rescues molybdenum cofactor-deficient C. elegans. |
| ジャーナル | Genes Dev |
| Abstract |
The molybdenum cofactor (Moco) is a 520-Da prosthetic group that is synthesized in all domains of life. In animals, four oxidases (among them sulfite oxidase) use Moco as a prosthetic group. Moco is essential in animals; humans with mutations in genes that encode Moco biosynthetic enzymes display lethal neurological and developmental defects. Moco supplementation seems a logical therapy; however, the instability of Moco has precluded biochemical and cell biological studies of Moco transport and bioavailability. The nematode Caenorhabditis elegans can take up Moco from its bacterial diet and transport it to cells and tissues that express Moco-requiring enzymes, suggesting a system for Moco uptake and distribution. Here we show that protein-bound Moco is the stable, bioavailable species of Moco taken up by C. elegans from its diet and is an effective dietary supplement, rescuing a Celegans model of Moco deficiency. We demonstrate that diverse Moco:protein complexes are stable and bioavailable, suggesting a new strategy for the production and delivery of therapeutically active Moco to treat human Moco deficiency. |
| 巻・号 | 35(3-4) |
| ページ | 212-217 |
| 公開日 | 2021-2-1 |
| DOI | 10.1101/gad.345579.120 |
| PII | gad.345579.120 |
| PMID | 33446569 |
| PMC | PMC7849362 |
| MeSH | Animals Bacteria / metabolism Biological Transport Caenorhabditis elegans / metabolism* Coenzymes / administration & dosage* Coenzymes / deficiency Coenzymes / pharmacokinetics Humans Metal Metabolism, Inborn Errors / therapy* Metalloproteins / administration & dosage* Metalloproteins / deficiency Metalloproteins / pharmacokinetics Molybdenum Cofactors Protein Binding Pteridines / administration & dosage* Pteridines / pharmacokinetics |
| IF | 9.527 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 原核生物(大腸菌) | BW25113 JW0764 |