Skip to main content
PMC home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2006 Oct 13;33(1):113–121. doi: 10.1007/s00726-006-0412-0

Multi-layered network structure of amino acid (AA) metabolism characterized by each essential AA-deficient condition

N Shikata 1, Y Maki 2, Y Noguchi 3, M Mori 3, T Hanai 1, M Takahashi 3, M Okamoto 1
PMCID: PMC7088186  PMID: 17031477

Summary.

The concentrations of free amino acids in plasma change coordinately and their profiles show distinctive features in various physiological conditions; however, their behavior can not always be explained by the conventional flow-based metabolic pathway network. In this study, we have revealed the interrelatedness of the plasma amino acids and inferred their network structure with threshold-test analysis and multilevel-digraph analysis methods using the plasma samples of rats which are fed diet deficient in single essential amino acid.

In the inferred network, we could draw some interesting interrelations between plasma amino acids as follows: 1) Lysine is located at the top control level and has effects on almost all of the other plasma amino acids. 2) Threonine plays a role in a hub in the network, which has direct links to the most number of other amino acids. 3) Threonine and methionine are interrelated to each other and form a loop structure.

Keywords: Keywords: Plasma amino acids – Profile – Relation – Network – Threonine – Amino acid deficiency

References

  1. Allen RH, Stabler SP, Savage DG, Lindenbaum J. Metabolic abnormalities in cobalamin (vitamin B12) and folate deficiency. Faseb J. 1993;7:1344–1353. doi: 10.1096/fasebj.7.14.7901104. [DOI] [PubMed] [Google Scholar]
  2. Althaus IW, Chou JJ, Gonzales AJ, Deibel MR, Chou KC, Kezdy FJ, Romero DL, Aristoff PA, Tarpley WG, Reusser F. Steady-state kinetic studies with the non-nucleoside HIV-1 reverse transcriptase inhibitor U-87201E. J Biol Chem. 1993a;268:6119–6124. [PubMed] [Google Scholar]
  3. Althaus IW, Chou JJ, Gonzales AJ, Deibel MR, Chou KC, Kezdy FJ, Romero DL, Palmer JR, Thomas RC, Aristoff PA, et al. Kinetic studies with the non-nucleoside HIV-1 reverse transcriptase inhibitor U-88204E. Biochemistry. 1993b;32:6548–6554. doi: 10.1021/bi00077a008. [DOI] [PubMed] [Google Scholar]
  4. Althaus IW, Gonzales AJ, Chou JJ, Romero DL, Deibel MR, Chou KC, Kezdy FJ, Resnick L, Busso ME, So AG, et al. The quinoline U-78036 is a potent inhibitor of HIV-1 reverse transcriptase. J Biol Chem. 1993c;268:14875–14880. [PubMed] [Google Scholar]
  5. Banerjee R, Zou CG. Redox regulation and reaction mechanism of human cystathionine-beta-synthase: a PLP-dependent hemesensor protein. Arch Biochem Biophys. 2005;433:144–156. doi: 10.1016/j.abb.2004.08.037. [DOI] [PubMed] [Google Scholar]
  6. Borcsok E, Abeles RH. Mechanism of action of cystathionine synthase. Arch Biochem Biophys. 1982;213:695–707. doi: 10.1016/0003-9861(82)90600-2. [DOI] [PubMed] [Google Scholar]
  7. Chou KC. Two new schematic rules for rate laws of enzyme-catalysed reactions. J Theor Biol. 1981;89:581–592. doi: 10.1016/0022-5193(81)90030-8. [DOI] [PubMed] [Google Scholar]
  8. Chou KC. Graphic rules in steady and non-steady state enzyme kinetics. J Biol Chem. 1989;264:12074–12079. [PubMed] [Google Scholar]
  9. Chou KC. Applications of graph theory to enzyme kinetics and protein folding kinetics. Steady and non-steady-state systems. Biophys Chem. 1990;35:1–24. doi: 10.1016/0301-4622(90)80056-D. [DOI] [PubMed] [Google Scholar]
  10. Chou KC, Liu WM. Graphical rules for non-steady state enzyme kinetics. J Theor Biol. 1981;91:637–654. doi: 10.1016/0022-5193(81)90215-0. [DOI] [PubMed] [Google Scholar]
  11. Chou KC, Kezdy FJ, Reusser F. Kinetics of processive nucleic acid polymerases and nucleases. Anal Biochem. 1994;221:217. doi: 10.1006/abio.1994.1405. [DOI] [PubMed] [Google Scholar]
  12. Chou KC, Cai YD, Zhong WZ. Predicting networking couples for metabolic pathways of Arabidopsis. EXCLI J. 2006;5:55–65. [Google Scholar]
  13. Felig P. Amino acid metabolism in man. Annu Rev Biochem. 1975;44:933–955. doi: 10.1146/annurev.bi.44.070175.004441. [DOI] [PubMed] [Google Scholar]
  14. Ferenci P, Wewalka F. Plasma amino acids in hepatic encephalopathy. J Neural Transm [Suppl] 1978;14:87–94. [PubMed] [Google Scholar]
  15. Holm E, Sedlaczek O, Grips E. Amino acid metabolism in liver disease. Curr Opin Clin Nutr Metab Care. 1999;2:47–53. doi: 10.1097/00075197-199901000-00009. [DOI] [PubMed] [Google Scholar]
  16. Hong SY, Yang DH, Chang SK. The relationship between plasma homocysteine and amino acid concentrations in patients with end-stage renal disease. J Ren Nutr. 1998;8:34–39. doi: 10.1016/s1051-2276(98)90035-8. [DOI] [PubMed] [Google Scholar]
  17. Jimenez Jimenez FJ, Ortiz Leyba C, Morales Menedez S, Barros Perez M, Munoz Garcia J. Prospective study on the efficacy of branched-chain amino acids in septic patients. JPEN. 1991;15:252–261. doi: 10.1177/0148607191015003252. [DOI] [PubMed] [Google Scholar]
  18. Kadowaki M, Kanazawa T. Amino acids as regulators of proteolysis. J Nutr. 2003;133:2052S–2056S. doi: 10.1093/jn/133.6.2052S. [DOI] [PubMed] [Google Scholar]
  19. Kapke G, Davis L. Stereochemistry of the reaction of sheep liver threonine dehydratase. A nuclear magnetic resonance and optical rotatory dispersion study of its reaction pathway and products. Biochemistry. 1976;15:3745–3749. doi: 10.1021/bi00662a016. [DOI] [PubMed] [Google Scholar]
  20. Kimball SR. Regulation of global and specific mRNA translation by amino acids. J Nutr. 2002;132:883–886. doi: 10.1093/jn/132.5.883. [DOI] [PubMed] [Google Scholar]
  21. Kuzmic P, Ng KY, Heath TD. Mixtures of tight-binding enzyme inhibitors. Kinetic analysis by a recursive rate equation. Anal Biochem. 1992;200:68–73. doi: 10.1016/0003-2697(92)90278-F. [DOI] [PubMed] [Google Scholar]
  22. Lin SX, Neet KE. Demonstration of a slow conformational change in liver glucokinase by fluorescence spectroscopy. J Biol Chem. 1990;265:9670–9675. [PubMed] [Google Scholar]
  23. Maki Y, Takahashi Y, Arikawa Y, Watanabe S, Aoshima K, Eguchi Y, Ueda T, Aburatani S, Kuhara S, Okamoto M. An integrated comprehensive workbench for inferring genetic networks: voyagene. J Bioinform Comput Biol. 2004;2:533–550. doi: 10.1142/S0219720004000727. [DOI] [PubMed] [Google Scholar]
  24. Maki Y, Tominaga D, Okamoto M, Watanabe S, Eguchi Y. Development of a system for the inference of large scale genetic networks. Pac Symp Biocomput. 2001;6:446–458. doi: 10.1142/9789814447362_0044. [DOI] [PubMed] [Google Scholar]
  25. Nicholson JK, Lindon JC, Holmes E. ‘Metabonomics’: understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica. 1999;29:1181–1189. doi: 10.1080/004982599238047. [DOI] [PubMed] [Google Scholar]
  26. Noguchi Y, Zhang QW, Sugimoto T, Furuhata Y, Sakai R, Mori M, Takahashi M, Kimura T. Network analysis of plasma and tissue amino acids and the generation of an amino index for potential diagnostic use. Am J Clin Nutr. 2006;83:513S–519S. doi: 10.1093/ajcn/83.2.513S. [DOI] [PubMed] [Google Scholar]
  27. Scarselli M, Padula MG, Bernini A, Spiga O, Ciutti A, Leoncini R, Vannoni D, Marinello E, Niccolai N. Structure and function correlations between the rat liver threonine deaminase and aminotransferases. Biochim Biophys Acta. 2003;1645:40–48. doi: 10.1016/s1570-9639(02)00502-2. [DOI] [PubMed] [Google Scholar]
  28. Soeters PB, Fischer JE. Insulin, glucagon, aminoacid imbalance, and hepatic encephalopathy. Lancet. 1976;2:880–882. doi: 10.1016/S0140-6736(76)90541-9. [DOI] [PubMed] [Google Scholar]
  29. Stabler SP, Lindenbaum J, Savage DG, Allen RH. Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency. Blood. 1993;81:3404–3413. [PubMed] [Google Scholar]
  30. Tudor I, Tanase-Mogos I, Tanasie E, Badescu E, Rascanu M. A study of aminoacidemia and aminoaciduria in epileptic children. Neurol Psychiatr (Bucur) 1976;14:277–282. [PubMed] [Google Scholar]
  31. Wang M, Yao JS, Huang ZD, Xu ZJ, Liu GP, Zhao HY, Wang XY, Yang J, Zhu YS, Chou KC. A new nucleotide-composition based fingerprint of SARS-CoV with visualization analysis. Med Chem. 2005;1:39–47. doi: 10.2174/1573406053402505. [DOI] [PubMed] [Google Scholar]
  32. Watanabe A, Higashi T, Sakata T, Nagashima H. Serum amino acid levels in patients with hepatocellular carcinoma. Cancer. 1984;54:1875–1882. doi: 10.1002/1097-0142(19841101)54:9<1875::AID-CNCR2820540918>3.0.CO;2-O. [DOI] [PubMed] [Google Scholar]
  33. Watanabe A, Takei N, Hayashi S, Nagashima H. Serum neutral amino acid concentrations in cirrhotic patients with impaired carbohydrate metabolism. Acta Med Okayama. 1983;37:381–384. doi: 10.18926/AMO/32395. [DOI] [PubMed] [Google Scholar]
  34. Watanabe F, Nakano Y. [Vitamin B12] Nippon Rinsho. 1999;57:2205–2210. [PubMed] [Google Scholar]
  35. Xiao X, Shao S, Ding Y, Huang Z, Chen X, Chou KC. An application of gene comparative image for predicting the effect on replication ratio by HBV virus gene missense mutation. J Theor Biol. 2005a;235:555–565. doi: 10.1016/j.jtbi.2005.02.008. [DOI] [PubMed] [Google Scholar]
  36. Xiao X, Shao S, Ding Y, Huang Z, Chen X, Chou KC. Using cellular automata to generate image representation for biological sequences. Amino Acids. 2005b;28:29–35. doi: 10.1007/s00726-004-0154-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Xiao X, Shao S, Ding Y, Huang Z, Chou KC. Using cellular automata images and pseudo amino acid composition to predict protein subcellular location. Amino Acids. 2006a;30:49–54. doi: 10.1007/s00726-005-0225-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Xiao X, Shao SH, Chou KC. A probability cellular automaton model for hepatitis B viral infections. Biochem Biophys Res Commun. 2006b;342:605–610. doi: 10.1016/j.bbrc.2006.01.166. [DOI] [PubMed] [Google Scholar]
  39. Yeang CH, Mak HC, McCuine S, Workman C, Jaakkola T, Ideker T. Validation and refinement of gene-regulatory pathways on a network of physical interactions. Genome Biol. 2005;6:R62. doi: 10.1186/gb-2005-6-7-r62. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Zhang CT, Chou KC. An analysis of base frequencies in the anti-sense strands corresponding to the 180 human protein coding sequences. Amino Acids. 1996;10:253–262. doi: 10.1007/BF00807327. [DOI] [PubMed] [Google Scholar]

Articles from Amino Acids are provided here courtesy of Nature Publishing Group

RESOURCES