The kynurenine metabolic pathway in the eye: studies on 3-hydroxykynurenine, a putative cataractogenic compound.
The rabbit lens has an elevated content of 3-hydroxykynurenine (30HKYN) in spite of a very low activity of the enzymes leading to its synthesis. The iris/ciliary body, on the contrary, has very high activity of 30HKYN synthesizing enzymes but a content of 30HKYN lower than that of the lens. These observations suggest that 30HKYN is formed in the iris/ ciliary body, released into the aqueous humor and then taken up into the lens where it may be used for the synthesis of UV filtering products. An excessive accumulation of 30HKYN in the lens has been associated with cataract formation. We found that available selective inhibitors of kynurenine hydroxylase reduced 30HKYN synthesis in both the lens and the iris/ciliary body.
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
A
A
Chiarugi
E
E
Rapizzi
F
F
Moroni
F
F
Moroni
D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002386:Cataract / Q000209:etiology*; D002924:Ciliary Body / Q000378:metabolism; D005123:Eye / Q000378:metabolism*; D006867:Hydrolases / Q000032:analysis; D007498:Iris / Q000378:metabolism; D007737:Kynurenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism*; D050601:Kynurenine 3-Monooxygenase; D007908:Lens, Crystalline / Q000378:metabolism; D008190:Lyases; D008297:Male; D006899:Mixed Function Oxygenases / Q000032:analysis / Q000037:antagonists & inhibitors; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014018:Tissue Distribution; D000637:Transaminases / Q000032:analysis; D014366:Tryptophan Oxygenase / Q000032:analysis
C110196:Ro 61-8048; D013449:Sulfonamides; D013844:Thiazoles; C086214:(3-nitrobenzoyl)alanine; C005045:3-hydroxykynurenine; D007737:Kynurenine; D006899:Mixed Function Oxygenases; D014366:Tryptophan Oxygenase; D050601:Kynurenine 3-Monooxygenase; D000637:Transaminases; C427605:glutamine - phenylpyruvate transaminase; C021481:kynurenine-oxoglutarate transaminase; D006867:Hydrolases; C021480:kynureninase; D008190:Lyases; D000409:Alanine