Kynurenine 3-hydroxylase in brain: species activity differences and effect of gerbil cerebral ischemia.
We have developed a rapid and highly sensitive assay for brain kynurenine 3-hydroxylase activity. The present study determined some characteristics and species differences of kynurenine 3-hydroxylase activity in brain and evaluated the response of this enzyme to cerebral ischemia. The kynurenine 3-hydroxylase assay is based on the conversion of L-kynurenine to 3-hydroxykynurenine in vitro and the quantification of 3-hydroxykynurenine by high-performance liquid chromatography. Kynurenine 3-hydroxylase activity was detected in human, macaque, rat, mouse, and gerbil brain. Regional gerbil brain activities ranged from 20 to 50 nmol/g/h, while kynurenine 3-hydroxylase activities in other species were one order of magnitude lower. Kynurenine 3-hydroxylase was also detected in lung, kidney, spleen, intestine, and liver of gerbils, with activities larger than in brain. Delayed increases in the activity of kynurenine 3-hydroxylase occur in several brain regions following transient ischemia in gerbils. These changes are particularly marked in regions that showed the most extensive brain damage (hippocampus and striatum). Kynurenine 3-hydroxylase may have an important role in determining the flux of kynurenine in brain.
Saito
K
K
Section on Analytical Biochemistry, National Institute of Mental Health, Bethesda, Maryland 20892.
Quearry
B J
BJ
Saito
M
M
Nowak
T S
TS
Markey
S P
SP
Heyes
M P
MP
D000818:Animals; D001921:Brain / Q000201:enzymology*; D005260:Female; D005849:Gerbillinae; D006801:Humans; D007422:Intestines / Q000201:enzymology; D002546:Ischemic Attack, Transient / Q000201:enzymology*; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D050601:Kynurenine 3-Monooxygenase; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013154:Spleen / Q000201:enzymology; D013574:Synaptosomes / Q000201:enzymology
D006899:Mixed Function Oxygenases; D050601:Kynurenine 3-Monooxygenase