A low molecular weight lead-binding protein in brain attenuates lead inhibition of delta-aminolevulinic acid dehydratase: comparison with a renal lead-binding protein.
A low molecular weight high-affinity lead-binding protein (PbBP) in kidney appears to account, at least in part, for the relative insensitivity of renal delta-aminolevulinic acid dehydratase (ALAD) to Pb inhibition. A PbBP is also known to exist in brain cytosol but is not a major Pb-binding constituent in liver. This study was undertaken to examine the relative sensitivity of brain and liver ALAD to Pb inhibition in vitro and to determine if inhibition of hepatic ALAD by Pb could be reversed by addition of partially purified brain PbBP to liver cytosol. This effect was also compared with that of a previously described renal PbBP. Finally, the mechanism(s) of reversal of Pb inhibition of ALAD by these tissue-specific PbBPs were studied. A concentration-dependent reversal of Pb-induced inhibition of hepatic ALAD activity was observed for both brain and kidney PbBPs. Inhibition of hepatic ALAD activity by 0.1 to 1.6 microM Pb was partially reversed by a single concentration of brain PbBP. No differences in sensitivity of ALAD to Pb inhibition in various brain regions were observed. Kinetic analysis of both brain and liver ALAD activity at an IC50 Pb showed a "mixed" or noncompetitive inhibition pattern. Addition of brain PbBP reduced markedly the inhibitory effects of Pb on the Vmax of the liver enzyme. Incubation of 65Zn-labeled PbBP fractions from brain and kidney with purified bovine liver ALAD demonstrated that the PbBPs donate Zn to ALAD.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping; D002352:Carrier Proteins / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D007854:Lead / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors*; D051381:Rats
D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D007854:Lead; D000623:Porphobilinogen Synthase