Senescence marker protein 30 functions as gluconolactonase in l -ascorbic acid biosynthesis, and its knockout mice are prone to scurvy
| Autor: | Kentaro Shimokado, Morimitsu Nishikimi, Sataro Goto, Yasunori Sato, Akihito Ishigami, Yoko Inai, Yoshitaka Kondo, Sachiho Kubo, Naoki Maruyama, Setsuko Handa |
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| Rok vydání: | 2006 |
| Předmět: |
Vitamin
Aging Molecular Sequence Data Ascorbic Acid Substrate Specificity Mice chemistry.chemical_compound In vivo Lactonase Animals Amino Acid Sequence Mice Knockout chemistry.chemical_classification Multidisciplinary Sequence Homology Amino Acid biology Vitamin C Body Weight Calcium-Binding Proteins Intracellular Signaling Peptides and Proteins Biological Sciences Ascorbic acid Rats Amino acid Kinetics chemistry Biochemistry Knockout mouse biology.protein Gluconolactonase Scurvy Sulfotransferases Carboxylic Ester Hydrolases Sequence Alignment Biomarkers |
| Zdroj: | Proceedings of the National Academy of Sciences. 103:5723-5728 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0511225103 |
| Popis: | We originally identified senescence marker protein 30 (SMP30) as a distinctive protein whose expression decreases in an androgen-independent manner with aging. Here, we report its sequence homology found in two kinds of bacterial gluconolactonases (GNLs) by using the blast search. Then, through a biochemical study, we identify SMP30 as the lactone-hydrolyzing enzyme GNL of animal species. SMP30 purified from the rat liver had lactonase activity toward various aldonolactones, such as d - and l -glucono-δ-lactone, d - and l -gulono-γ-lactone, and d - and l -galactono-γ-lactone, with a requirement for Zn 2+ or Mn 2+ as a cofactor. Furthermore, in SMP30 knockout mice, no GNL activity was detectable in the liver. Thus, we conclude that SMP30 is a unique GNL in the liver. The lactonase reaction with l -gulono-γ-lactone is the penultimate step in l -ascorbic acid (AA) biosynthesis, and the essential role of SMP30 in this synthetic process was verified here by a nutritional study using SMP30 knockout mice. These knockout mice ( n = 6), fed a vitamin C-deficient diet, did not thrive; i.e., they displayed symptoms of scurvy such as bone fracture and rachitic rosary and then died by 135 days after the start of receiving the deficient diet. The AA levels in their livers and kidneys at the time of death were d -glucurono-γ-lactone operates in vivo , although its flux is fairly small. |
| Databáze: | OpenAIRE |
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