Similar pattern of inhibition of tryptophan pyrrolase activity by fluoxetine hydrochloride in both sexes of rats.
Compounds targeting the individual enzymes of kynurenine-nicotinamide pathway have led to new neuropharmacological concepts and provide novel opportunities for therapeutic intervention. Tryptophan pyrrolase (Tryptophan-2, 3-dioxygenase; EC 1.13.11.11), a metalloprotein, is the first and rate limiting enzyme of the most important pathway for tryptophan metabolism via kynurenine-nicotinamide pathway in the liver and therefore plays a key role in regulating the physiological flux of tryptophan in to relevant metabolic pathways like synthesis of neurotransmitter, serotonin in the brain. Fluoxetine, a clinically proven antidepressant, have shown statistically significant inhibition of hepatic tryptophan pyrrolase activities (holo, total and apo form) in both the sexes of rats at 10 & 30 mg/kg doses. Despite elevated holo-enzyme form of tryptophan pyrrolase in female rats, we have found similar inhibition of tryptophan pyrrolase activity by fluoxetine hydrochloride in both male and female rats. The results are discussed in relation to gender differences in the enzyme activity and its possible role in pathophysiology of depression in females.
Sherkheli
Muhammad Azhar
MA
Department of Biochemistry, University of Karachi, Karachi-75270, Pakistan.
Bano
Samina
S