engleski

Studies of ochratoxin A-induced inhibition of phenylalanine hydroxylase and its reversal by phenylalanine

Ochratoxin A(OTA) is a nephrotoxic, hepatotoxic, and teratogenic mycotoxin produced by storage molds ona a variety of foodstuffs. Its chemical structure is composed of an isocumarin part linked to L-phenylalanine. Inhibition of phenylalanine hydroxylase and other enzymes that use phenylanine as substrate is based on this structural homology. We have examined the effects of low doses of ochratoxin A on the acitivity of phenylanine hydroxylase in kidney and in liver of experimental animals. Daily administration of ochratoxin A (5 ug/kg bw, for 10 and 35 days, respectively) caused a significant reduction in phenylalanine hydrohylase activity. Inhibition was more pronounced in liver than in kidney, although actual ochratoxin A concentration was higher in the kidney tissue. We observed an apparent increase in the affinity of phenylanine hydroxylase for substrate following OTA administration to animals. However, simple competitive inhibition was observed for both tissues in vitro. Simultaneous application of ochratoxin A with phenylanine could reduce inhibition of phenylanine hydroxylase, in particular in liver. Enzyme acitivity was almost completely preserved after 35 days of combined treatment. The results obtained suggest that daily administration of ochratoxin A in low doses produced an inhbitory effect that could be diminished by competitive action of L-phenylanine.

ochratoxin A; phenylanaine hydroxylase; experimental endemic nephropathy

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