Neurotoxic action of lead: effect on tetrahydrobiopterin metabolism in the rat.
The effects of lead, a known neurotoxin on the metabolism of a vital tetrahydrobiopterin cofactor for the hydroxylation enzymes tyrosine hydroxylase, phenylalanine hydroxylase and tryptophan hydroxylase, have been investigated. Reduced availability of this pteridine has the potential to reduce the level of the neurotransmitters noradrenaline, adrenaline and 5-hydroxytryptophan in the brain. Using the rat as a model, increases in tetrahydrobiopterin concentration and in the activity of dihydropteridine reductase, an enzyme involved in tetrahydrobiopterin metabolism, were observed after exposure to lead via the drinking water. Possible explanations for this increased level of tetrahydrobiopterin relate to alterations in the balance between synthesis and salvage of this co-factor.
McIntosh
M J
MJ
Meredith
P A
PA
Moore
M R
MR
Goldberg
A
A
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000032:analysis; D001921:Brain / Q000378:metabolism*; D004093:Dihydropteridine Reductase / Q000378:metabolism; D007854:Lead / Q000097:blood / Q000494:pharmacology; D007855:Lead Poisoning / Q000378:metabolism*; D008297:Male; D009498:Neurotoxins; D011621:Pteridines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D009498:Neurotoxins; D011621:Pteridines; D001708:Biopterins; D007854:Lead; D004093:Dihydropteridine Reductase; C003402:sapropterin