Biochemistry and Molecular Biology of Ascorbic Acid Biosynthesis

Nishikimi, Morimitsu; Yagi, Kazuichi

doi:10.1007/978-1-4613-0325-1_2

Cited by 100 publications

(54 citation statements)

References 63 publications

(58 reference statements)

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“…VitC is an electron donor for a number of enzymatic systems, reducing potentially harmful free radicals by forming the more stable semidehydro-ascorbic acid, which does not regenerate enzymatically, but it is rather metabolised and discharged. 49 VitC may also have other beneficial pleiotropic actions, such as improvements in coronary microcirculation and endothelial function. 50,51 Animal studies and the use of drugs with antiinflammatory and antioxidant properties for the prophylaxis of postoperative AF, indicate an inflammation mediated mechanism for postoperative AF.…”

Section: 3234-38mentioning

confidence: 99%

Vitamin C for the Prevention of Postoperative Atrial Fibrillation after Cardiac Surgery: A Meta-Analysis

et al. 2016

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Section: 3234-38mentioning

confidence: 99%

Vitamin C for the Prevention of Postoperative Atrial Fibrillation after Cardiac Surgery: A Meta-Analysis

et al. 2016

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“…In mammalian metabolism, GNL is involved in L-ascorbic acid (AA) biosynthesis, catalyzing the lactonization of L-gulonic acid, the reverse reaction of lactone hydrolysis (7). The product L-gulono-␥-lactone is oxidized to AA (8)(9)(10). In this study, to further investigate the identity of SMP30, we have unequivocally proven that it is a GNL.…”

mentioning

confidence: 99%

Senescence marker protein 30 functions as gluconolactonase in l -ascorbic acid biosynthesis, and its knockout mice are prone to scurvy

Kondo

Inai

Sato

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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215

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We originally identified senescence marker protein 30 (SMP30) as a distinctive protein whose expression decreases in an androgenindependent 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-␦-lactone, D-and L-gulono-␥-lactone, and D-and L-galactono-␥-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-␥-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 <1.6% of those in WT control mice. In addition, by using the SMP30 knockout mouse, we demonstrate that the alternative pathway of AA synthesis involving D-glucurono-␥-lactone operates in vivo, although its flux is fairly small. aging ͉ osteogenic disorder ͉ vitamin C S enescence marker protein 30 (SMP30) is a 34-kDa protein whose tissue levels in the liver, kidney, and lung decrease with aging (1, 2). To examine the physiological function of SMP30, we established SMP30 knockout mice (3) and found that they were viable and fertile, although they were lower in body weight and shorter in life span than WT mice (4). Their livers were also far more susceptible to TNF-␣-and Fas-mediated apoptosis than those of WT mice, indicating that SMP30 may act to protect cells from apoptosis (3). The livers of SMP30 knockout mice showed abnormal accumulations of triglycerides, cholesterol, and phospholipids (4). In addition, the lungs of these knockout mice had enlarged alveolar airspaces during their first to sixth month of life (2). However, the molecular mechanism of SMP30 function has remained obscure.Recently, we reported that SMP30 acts as a hydrolase for diisopropyl phosphorofluoridate (5), a compound resembling chemical warfare nerve agents such as sarine, soman, and tabun. However, a physiological substrate for SMP30 must be present, because this compound is an artificial chemical. Our recent search for amino acid sequences resembling SMP30 was accomplished by using the BLAST program, which revealed that rat SMP30 is homologous with gluconolactonase (GNL) [EC 3.1.1.17], a lactone-hydrolyzing enzyme, of Nostoc punctiforme and Zymomonas mobilis (6). Therefore, we suspected that SMP30 is a GNL of animal species. In mammalian metabolism, GNL is...

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“…Mean values and standard deviations of blood pH, pO 2 , pCO 2 , and HCO 3 in a pulmonary contusion injury model in rats (n = 6; mean ± SD). To preserve against harm, cells contain a number of defense mechanisms, including well-documented endogenous antioxidant enzymes such as CAT, SOD, GSH-Px, glutathione reductase, and glutathione S-transferase and low-molecular-weight antioxidants such as glutathione (GSH) (4,5). Sulfhydryl groups (-SH) play an important role in producing a response to oxidative stress; GSH/glutaredoxin and thioredoxin systems are crucial components in maintaining redox homeostasis of the cell.…”

Section: Discussionmentioning

confidence: 99%

“…As an electron donor, vitamin C is a potent water-soluble antioxidant in humans. Antioxidant effects of vitamin C have been displayed in many experiments in vitro at the same time (4).…”

Section: Introductionmentioning

confidence: 99%

Vitamin C as an antioxidant: evaluation of its role on pulmonary contusion experimental model

Sirmali

Giniş²,

Sırmalı

et al. 2014

Turk J Med Sci

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Background/aim: To analyze the protective activity of vitamin C on the lungs by assessing biochemical and histopathological analysis after performing an experimental isolated lung contusion model. Materials and methods:Fifty-four male Sprague-Dawley male rats were used. The rats were randomly separated into 4 groups. Vitamin C (200 mg/kg) was injected intraperitoneally 30 min after trauma. Blood samples were obtained for myeloperoxidase (MPO), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities and malondialdehyde (MDA) levels. Blood gas analysis and bronchoalveolar lavage was performed. The lung tissue was also extracted for histopathological examination. Results:The lung contusion enhanced MDA, SOD, CAT, and MPO and diminished GSH-Px. Vitamin C administration after the pulmonary contusion was found to diminish the level of MDA and the activities of SOD, CAT, and MPO and to enhance the level of GSH-Px (P < 0.05). Contusion-induced disrupted gas analysis and leukocyte infiltration were both resolved by the vitamin C. Conclusion:The present results indicate that vitamin C administration attenuated the oxidative damage and morphological changes induced by pulmonary contusion in an experimental rat study.

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Biochemistry and Molecular Biology of Ascorbic Acid Biosynthesis

Cited by 100 publications

References 63 publications

Vitamin C for the Prevention of Postoperative Atrial Fibrillation after Cardiac Surgery: A Meta-Analysis

Vitamin C for the Prevention of Postoperative Atrial Fibrillation after Cardiac Surgery: A Meta-Analysis

Senescence marker protein 30 functions as gluconolactonase in l -ascorbic acid biosynthesis, and its knockout mice are prone to scurvy

Vitamin C as an antioxidant: evaluation of its role on pulmonary contusion experimental model

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