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The role of saccharopine pathway in diverse biological models

Grant number: 10/50114-4
Support Opportunities:Regular Research Grants
Duration: December 01, 2010 - May 31, 2013
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Paulo Arruda
Grantee:Paulo Arruda
Host Institution: Centro de Biologia Molecular e Engenharia Genética (CBMEG). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Lysine is synthesized in plants and bacteria through the aspartate pathway. This pathway, however, does not exist in animals and therefore, their amino acids end products are considered essential. On the other hand in fungi, lysine is synthesized trough the saccharopine pathway that in plants and animals is used for lysine degradation. We have shown that the saccharopine pathway controls the level of lysine in plant tissues while others have suggested that this pathway is involved in stress response and cell signaling processes not yet well understood. In plants and animals, de first two steps of the saccharopine pathway are catalyzed by lysine-ketoglutarate reductase (LKR) and saccharopine dehydrogenase (SDH) two enzymatic activities localized in two liked polypeptide domains forming a bifunctional enzyme. On the other hand, in yeast, were the saccharopine pathway is utilized for lysine synthesis, the two enzymatic activities are not linked and are localized in distinct chromosomes. In plants the LKR and SDH domains are interspersed by a ~120 amino acids polypeptide that in animals does not exist. The enzymatic activity of plant LKR is regulated by Ca2+, osmolites e ionic strength, while the animal enzyme does not respond to these agents. We have shown that lysine is the precursor of glutamate neurotransmitter. The LKR and SDH activities are present in the neurons where around 50% of glutamate is produced from lysine trough the saccharopine pathway. The aim of this project is to study the regulatory mechanisms underpin the saccharopine pathway in diverse organisms to get insight into the role of the pathway in plant development, metabolism and response to stresses. (AU)

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Scientific publications (6)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
KIYOTA, EDUARDO; PENA, IZABELLA AGOSTINHO; ARRUDA, PAULO. The saccharopine pathway in seed development and stress response of maize. PLANT CELL AND ENVIRONMENT, v. 38, n. 11, p. 2450-2461, . (12/00235-5, 10/50114-4)
NESHICH, IZABELLA A. P.; KIYOTA, EDUARDO; ARRUDA, PAULO. Genome-wide analysis of lysine catabolism in bacteria reveals new connections with osmotic stress resistance. ISME Journal, v. 7, n. 12, p. 2400-2410, . (12/00235-5, 10/50114-4)
ARRUDA, PAULO; NESHICH, IZABELLA PENA. Nutritional-rich and stress-tolerant crops by saccharopine pathway manipulation. FOOD AND ENERGY SECURITY, v. 1, n. 2, p. 141-147, . (12/00235-5, 10/50114-4)
PENA, IZABELLA A.; MARQUES, LYGIA A.; LARANJEIRA, ANGELO B. A.; YUNES, JOSE A.; EBERLIN, MARCOS N.; ARRUDA, PAULO. Simultaneous detection of lysine metabolites by a single LC-MS/MS method: monitoring lysine degradation in mouse plasma. SPRINGERPLUS, v. 5, . (13/23920-8, 10/50114-4, 12/00235-5)
PENA, IZABELLA AGOSTINHO; MARQUES, LYGIA AZEVEDO; LARANJEIRA, ANGELO B. A.; YUNES, JOSE A.; EBERLIN, MARCOS N.; MACKENZIE, ALEX; ARRUDA, PAULO. Mouse lysine catabolism to aminoadipate occurs primarily through the saccharopine pathway; implications for pyridoxine dependent epilepsy (PDE). BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v. 1863, n. 1, p. 121-128, . (13/23920-8, 10/50114-4, 12/00235-5)
DE MELLO SERRANO, GUILHERME COUTINHO; REZENDE E SILVA FIGUEIRA, THAIS; KIYOTA, EDUARDO; ZANATA, NATALIA; ARRUDA, PAULO. Lysine degradation through the saccharopine pathway in bacteria: LKR and SDH in bacteria and its relationship to the plant and animal enzymes. FEBS Letters, v. 586, n. 6, p. 905-911, . (10/50114-4)

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