Abstract
It is known that plasma serine and threonine concentrations are elevated in rats chronically fed an essential amino acid deficient diet, but the underlying mechanisms including related gene expressions or serine and threonine concentrations in liver remained to be elucidated. We fed rats lysine or valine deficient diet for 4 weeks and examined the mRNA expressions of serine synthesising (3-phosphoglycerate dehydrogenase, PHGDH) and serine/threonine degrading enzymes (serine dehydratase, SDS) in the liver. Dietary deficiency induced marked elevation of hepatic serine and threonine levels associated with enhancement of PHGDH mRNA expression and repression of SDS mRNA expression. Increases in plasma serine and threonine levels due to essential amino acid deficiency in diet were caused by marked increases in hepatic serine and threonine levels. Proteolytic responses to the amino acid deficiency may be lessened by storing amino radicals as serine and inducing anorexia through elevation of threonine.
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Abbreviations
- PHGDH:
-
3-Phosphoglycerate dehydrogenase
- SDS:
-
Serine dehydratase
References
Achouri Y, Robbi M, Van Schaftingen E (1999) Role of cysteine in the dietary control of the expression of 3-phosphoglycerate dehydrogenase in rat liver. Biochem J 344(Pt 1):15–21
Albrecht J, Jones EA (1999) Hepatic encephalopathy: molecular mechanisms underlying the clinical syndrome. J Neurol Sci 170:138–146
Anderson SA, Ralten DJ (eds) (1992) Safety of amino acids used as dietary supplements. Federation of American Societies for Experimental Biology (FASEB), Bethesda, pp 86–90
Davis JL, Fallon HJ (1970) Studies on the role of 3-phosphoglycerate dehydrogenase in the regulation of serine biosynthesis in rat liver. J Biol Chem 245:5838–5846
de Koning TJ, Poll-The BT, Jaeken J (1999) Continuing education in neurometabolic disorders—serine deficiency disorders. Neuropediatrics 30:1–4
de Koning TJ, Klomp LW, van Oppen AC, Beemer FA, Dorland L, van den Berg I, Berger R (2004) Prenatal and early postnatal treatment in 3-phosphoglycerate-dehydrogenase deficiency. Lancet 364:2221–2222
Desvergne B, Michalik L, Wahli W (2006) Transcriptional regulation of metabolism. Physiol Rev 86:465–514
Flodin NW (1997) The metabolic roles, pharmacology, and toxicology of lysine. J Am Coll Nutr 16:7–21
Gietzen DW, Rogers QR (2006) Nutritional homeostasis and indispensable amino acid sensing: a new solution to an old puzzle. Trends Neurosci 29:91–99
Greenberg DM, Ichihara A (1957) Further studies on the pathway of serine formation from carbohydrate. J Biol Chem 224:331–340
Hao S, Sharp JW, Ross-Inta CM, McDaniel BJ, Anthony TG, Wek RC, Cavener DR, McGrath BC, Rudell JB, Koehnle TJ, Gietzen DW (2005) Uncharged tRNA and sensing of amino acid deficiency in mammalian piriform cortex. Science 307:1776–1778
Hutchison SN, Zarghami NS, Cusick PK, Longenecker JB, Haskell BE (1983) The effect of valine deficiency on neutral amino acid patterns in plasma and brain of the rat. J Nutr 113:2164–2170
Ishikawa E, Ninagawa T, Suda M (1965) Hormonal and dietary control of serine dehydratase in rat liver. J Biochem 57:506–513
Jaeken J, Detheux M, Van Maldergem L, Foulon M, Carchon H, Van Schaftingen E (1996) 3-Phosphoglycerate dehydrogenase deficiency: an inborn error of serine biosynthesis. Arch Dis Child 74:542–545
Kadowaki M, Kanazawa T (2003) Amino acids as regulators of proteolysis. J Nutr 133:2052S–2056S
Kanamoto R, Su Y, Pitot HC (1991) Effects of glucose, insulin, and cAMP on transcription of the serine dehydratase gene in rat liver. Arch Biochem Biophys 288:562–566
Klomp LW, de Koning TJ, Malingre HE, van Beurden EA, Brink M, Opdam FL, Duran M, Jaeken J, Pineda M, Van Maldergem L et al (2000) Molecular characterization of 3-phosphoglycerate dehydrogenase deficiency—a neurometabolic disorder associated with reduced l-serine biosynthesis. Am J Hum Genet 67:1389–1399
Lopez-Flores I, Barroso JB, Valderrama R, Esteban FJ, Martinez-Lara E, Luque F, Peinado MA, Ogawa H, Lupianez JA, Peragon J (2005) Serine dehydratase expression decreases in rat livers injured by chronic thioacetamide ingestion. Mol Cell Biochem 268:33–43
Lopez-Flores I, Peragon J, Valderrama R, Esteban FJ, Luque F, Peinado MA, Aranda F, Lupianez JA, Barroso JB (2006) Downregulation in the expression of the serine dehydratase in the rat liver during chronic metabolic acidosis. Am J Physiol Regul Integr Comp Physiol 291:R1295–R1302
Mauron J, Mottu F, Spohr G (1973) Reciprocal induction and repression of serine dehydratase and phosphoglycerate dehydrogenase by proteins and dietary-essential amino acids in rat liver. Eur J Biochem 32:331–342
Maurin AC, Jousse C, Averous J, Parry L, Bruhat A, Cherasse Y, Zeng H, Zhang Y, Harding HP, Ron D, Fafournoux P (2005) The GCN2 kinase biases feeding behavior to maintain amino acid homeostasis in omnivores. Cell Metab 1:273–277
Noguchi Y, Zhang QW, Sugimoto T, Furuhata Y, Sakai R, Mori M, Takahashi M, Kimura T (2006) Network analysis of plasma and tissue amino acids and the generation of an amino index for potential diagnostic use. Am J Clin Nutr 83:513S–519S
Ogawa H, Fujioka M, Su Y, Kanamoto R, Pitot HC (1991) Nutritional regulation and tissue-specific expression of the serine dehydratase gene in rat. J Biol Chem 266:20412–20417
Pitot HC, Peraino C (1964) Studies on the induction and repression of enzymes in rat liver. I. Induction of threonine dehydrase and ornithine-delta-transaminase by oral intubation of casein hydrolysate. J Biol Chem 239:1783–1788
Salway J (2004) Metabolism at a glance (at a glance), 3rd edn edn. Blackwell, Malden, pp 74–77
Schmittgen TD, Zakrajsek BA (2000) Effect of experimental treatment on housekeeping gene expression: validation by real-time, quantitative RT-PCR. J Biochem Biophys Methods 46:69–81
Shikata N, Maki Y, Noguchi Y, Mori M, Hanai T, Takahashi M, Okamoto M (2007) Multi-layered network structure of amino acid (AA) metabolism characterized by each essential AA-deficient condition. Amino Acids 33:113–121
Simpson DA, Feeney S, Boyle C, Stitt AW (2000) Retinal VEGF mRNA measured by SYBR green I fluorescence: a versatile approach to quantitative PCR. Mol Vis 6:178–183
Snell K (1975) Mitochondrial-cytosolic interrelationships involved in gluconeogenesis from serine in rat liver. FEBS Lett 55:202–205
Snell K (1984) Enzymes of serine metabolism in normal, developing and neoplastic rat tissues. Adv Enzyme Regul 22:325–400
Vabulas RM, Hartl FU (2005) Protein synthesis upon acute nutrient restriction relies on proteasome function. Science 310:1960–1963
Acknowledgements
We thank Hifumi Kumeya, Terumi Nagai, Akiko Todokoro, Rie Nishijima and Akira Morita for their excellent technical assistance.
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Nagao, K., Bannai, M., Seki, S. et al. Adaptational modification of serine and threonine metabolism in the liver to essential amino acid deficiency in rats. Amino Acids 36, 555–562 (2009). https://doi.org/10.1007/s00726-008-0117-7
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DOI: https://doi.org/10.1007/s00726-008-0117-7