Cited by 123Sirtuins and Resveratrol in MedicineBiochemical and Molecular ResearchAmino Acid Enzymes and Metabolism

Overexpression of SIRT5 confirms its involvement in deacetylation and activation of carbamoyl phosphate synthetase 1

Ogura, Masahito, Nakamura, Yasuhiko, Tanaka, Daisuke, Zhuang, Xiaotong, Fujita, Yoshihito, Obara, Akio, Hamasaki, Akihiro, Hosokawa, Masaya +1 more·2010·Biochemical and Biophysical Research Communications

Abstract

SIR2 protein, an NAD-dependent deacetylase, is localized to nucleus and is involved in life span extension by calorie restriction in yeast. In mammals, among the seven SIR2 homologues (SIRT1-7), SIRT3, 4, and 5 are localized to mitochondria. As SIRT5 mRNA levels in liver are increased by fasting, the physiological role of SIRT5 was investigated in liver of SIRT5-overexpressing transgenic (SIRT5 Tg) mice. We identified carbamoyl phosphate synthetase 1 (CPS1), a key enzyme of the urea cycle that catalyzes condensation of ammonia with bicarbonate to form carbamoyl phosphate, as a target of SIRT5 by two-dimensional electrophoresis comparing mitochondrial proteins in livers of SIRT5 Tg and wild-type mice. CPS1 protein was more deacetylated and activated in liver of SIRT5 Tg mice than in wild-type. In addition, urea production was upregulated in hepatocytes of SIRT5 Tg mice. These results agree with those of a previous study using SIRT5 knockout (KO) mice. Because ammonia generated during fasting is toxic, SIRT5 protein might play a protective role by converting ammonia to non-toxic urea through deacetylation and activation of CPS1.

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Crossref · 10.1016/j.bbrc.2010.01.081

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Authors
Ogura, M., Nakamura, Y., Tanaka, D., Zhuang, X., Fujita, Y., Obara, A., Hamasaki, A., Hosokawa, M., & Inagaki, N.
Affiliations
Kyoto University (JP)
Corresponding author
Inagaki, Nobuya
Venue
Biochemical and Biophysical Research Communications
Publisher
Elsevier BV
Published
2010-02
Volume
393
Issue
1
Pages
73-78
ISSN
0006-291X (ISSN-L)
OpenAlex
W2076186906
Cited by
121
References
28
Citations by year
2026: 5 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 11 · 2021: 8 · 2020: 3 · 2019: 3 · 2018: 6 · 2017: 8 · 2016: 11 · 2015: 10 · 2014: 7 · 2013: 9 · 2012: 9
FWCI
3.96
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemical and Biophysical Research Communications (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Kyoto University
  • Ministry of Education, Culture, Sports, Science and Technology
  • Ministry of Health, Labour and Welfare
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
SIRT5, CPS1, protein deacetylation, enzyme activation, urea cycle, ammonia detoxification, liver, fasting, transgenic mice, mitochondrial proteins
MeSH terms
Acetylation, Amino Acid Sequence, Ammonia, Animals, Carbamoyl-Phosphate Synthase (Ammonia), Enzyme Activation, Fasting, Mice, Transgenic, Mitochondria, Liver, Molecular Sequence Data, Peptides, RNA, Messenger, Urea, Up-Regulation, Mice, Knockout, Hepatocytes, Sirtuins, Mice

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