Changes in kynurenine pathway metabolism in the brain, liver and kidney of aged female Wistar rats.
The kynurenine pathway of tryptophan catabolism plays an important role in several biological systems affected by aging. We quantified tryptophan and its metabolites kynurenine (KYN), kynurenine acid (KYNA), picolinic acid (PIC) and quinolinic acid (QUIN), and activity of the kynurenine pathway enzymes indoleamine 2,3-dioxygenase (IDO), tryptophan 2,3-dioxygenase (TDO) and quinolinic acid phosphoribosyltransferase (QPRTase), in the brain, liver and kidney of young, middle-aged and old female Wistar rats. Tryptophan levels and TDO activity decreased in all tissues with age. In contrast, brain IDO activity increased with age, while liver and kidney IDO activity decreased with age. The levels of KYN, KYNA, QUIN and PIC in brain all increased with age, while the levels of KYN in the liver and kidney showed a tendency to decrease. The levels of KYNA in the liver did not change, but the levels of KYNA in the kidney increased. The levels of PIC and QUIN increased significantly in the liver but showed a tendency to decrease in the kidney. QPRTase activity in both brain and liver decreased with age but was elevated in the kidney in middle-aged (12-month-old) rats. These age-associated changes in tryptophan metabolism have the potential to impact upon major biological processes, including lymphocyte function, pyridine (NAD(P)(H)) synthesis and N-methyl-d-aspartate (NMDA)-mediated synaptic transmission, and may therefore contribute to several degenerative changes of the elderly.
University of New South Wales, Faculty of Medicine, Sydney, NSW, Australia.
Nady
N
Braidy
Gilles J
GJ
Guillemin
Hussein
H
Mansour
Tailoi
T
Chan-Ling
Ross
R
Grant
D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007737:Kynurenine / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D010430:Pentosyltransferases / Q000378:metabolism; D010848:Picolinic Acids / Q000378:metabolism; D017378:Quinolinic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D000637:Transaminases / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism; D014366:Tryptophan Oxygenase / Q000378:metabolism; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating)
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D010848:Picolinic Acids; D007737:Kynurenine; D014364:Tryptophan; D014366:Tryptophan Oxygenase; D010430:Pentosyltransferases; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating); D000637:Transaminases; C021481:kynurenine-oxoglutarate transaminase; D017378:Quinolinic Acid; C030614:picolinic acid