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Metabolomic analysis of sulfur-containing substances and polyamines in regenerating rat liver

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Abstract

We studied the significance of alterations in the metabolomics of sulfur-containing substances in rapidly regenerating rat livers. Male rats were subjected to two-thirds partial hepatectomy (PHx), and the changes in hepatic levels of major sulfur-containing amino acids and related substances were monitored for 2 weeks. Liver weight began to increase from 24 h after the surgery, and appeared to recover fully in 2 weeks. Serum alanine aminotransferase and aspartate aminotransferase activities were elevated immediately after the surgery and returned slowly to normal levels in 2 weeks. Methionine, S-adenosylmethionine (SAM), cystathionine and cysteine were increased rapidly and remained elevated for longer than 1 week. Hepatic glutathione concentration was increased gradually for 24 h, and then decreased thereafter, whereas hypotaurine was elevated drastically right after the surgery. Hepatic concentrations of polyamines were altered significantly by PHx. In the hepatectomized livers putrescine concentration was elevated rapidly, reaching a level 40- to 50-fold greater than normal in 6–12 h. Ornithine, the metabolic substrate for putrescine synthesis, was also elevated markedly. Spermidine was increased significantly, whereas spermine was depressed below normal, which appeared to be due to the increased consumption of decarboxylated SAM for spermidine biosynthesis. The results show that the metabolomics of sulfur-containing amino acids and related substances is altered profoundly in regenerating rat livers until the original weight is recovered. Hepatic concentrations of polyamines after PHx are closely associated with the alteration in the metabolomics of sulfur-containing substances. The implication of these changes in the progression of liver regeneration is discussed.

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Abbreviations

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

CβS:

Cystathionine β-synthase

CDC:

Cysteine sulfinate decarboxylase

CDO:

Cysteine dioxygenase

CγL:

Cystathionine γ-lyase

dcSAM:

Decarboxylated S-adenosylmethionine

eIF5A:

Eukaryotic translation initiation factor 5A

GCL:

γ-Glutamylcysteine ligase

GSH:

Glutathione

MAT:

Methionine adenosyltransferase

PHx:

Partial hepatectomy

ROS:

Reactive oxygen species

SAH:

S-adenosylhomocyteine

SAM:

S-adenosylmethionine

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Acknowledgments

This work was supported by National Research Foundation (NRF) Grants (No. R01-2008-000-10622-0 and No. 2009-0083533) funded by the Ministry of Education, Science and Technology (MEST), Korea.

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Authors and Affiliations

  1. College of Pharmacy, Seoul National University, San 56-1 Shinrim-Dong, Kwanak-Ku, Seoul, 151-742, Korea

    Young S. Jung, Sun J. Kim, Do Y. Kwon & Young C. Kim

  2. Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1 Shinrim-Dong, Kwanak-Ku, Seoul, Korea

    Young C. Kim

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  1. Young S. Jung
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  2. Sun J. Kim
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  3. Do Y. Kwon
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  4. Young C. Kim
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Correspondence to Young C. Kim.

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Jung, Y.S., Kim, S.J., Kwon, D.Y. et al. Metabolomic analysis of sulfur-containing substances and polyamines in regenerating rat liver. Amino Acids 42, 2095–2102 (2012). https://doi.org/10.1007/s00726-011-0946-7

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  • DOI: https://doi.org/10.1007/s00726-011-0946-7

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