The effects of lead acetate on respiration in cerebral and cerebellar mitochondria from immature and adult rats were studied polarographically. With all substrates low lead concentrations produced an increase in respiration. Higher concentrations produced an inhibition of both this lead-induced respiration and ADP-dependent (State 3) respiration. Lead-induced respiration required inorganic phosphate and was inhibited by oligomycin, suggesting a coupling to oxidative phosphorylation. Inhibition of respiration was produced by much lower lead concentrations with NAD-linked citric acid cycle substrates than with succinate or alpha-glycerophosphate. In partially disrupted mitochondria, NAD-linked substrate oxidation was inhibited at lead concentrations which did not affect NADH oxidation. Thus, in brain mitochondria the NAD-linked dehydrogenases, located in the matrix space, were more sensitive to inhibition by lead than were inner membrane enzymes. All in vitro lead effects on mitochondrial respiration were comparable in cerebral and cerebellar mitochondria isolated from both immature and adult rats.

In the ndult rat, fed 2, the activity of jejunal sucreae shows a diurnal rhythm with a peak during the dark period. Ontogenitally this enzyme doe^ not appear until approximately the 16th postnatal day; its activity then rises rapidly and re ache^ adult levels by the 35th day. Our aim was to determine whether the diurnal rhythm is present from the outset or appeers only after sucrase has attaine6 adult levels. Rat pups were raised in litters of 9 with a li~htldark cycle of l?.h. Solid food and water were available to mothers and pups at all times and mothers were normally removed on the ?let postnatal day. Four litters were studied during the 24h period beginninu at Dam on the 19th day. One pup from each litter was removed for assay every 3h. Jejunal sucrase shoved considerable variation between pups, but there was no discernable pattern with time. In contrast, when the experiment was repeated with pups aaed 22 days, there was a distinct peak in sucrase activity during the early part of the dnrk period. In order to determine whether the rhythm la cued by the procesm of weaning. two litters were raised on a feeding schedule which ensured that maternal milk was the only food available to the pupa. h%en studied during the 24h period beginning on the 22nd day, the jejunal sucrase activity of these pups exhibited no rhythm. It is concluded that some component of solid food is responsible for the usual appearance of the diurnal rhythm of this enzyme. --0xid;tive'phosphorylation was measured polaribraphically before and after addina lead acetate to cerebral and cerebellar mitochondria isolatei from two week old and adult rats. With glutamate and malate as substrates. lead acetate (0.25 mM) produced a transient increase in respiration followed by complete inhibition of ADP-dependent respiration. The inhibition was not relieved by dinitrophenol or by freezing and thawing the mitochondria. NAOH-supported respiration, in frozen and thawed mitochondria, was not affected by these low concentrations suggesting that lead acts on substrate transport or dehydrogenases. With succinate as substrate, inorganic lead produced an increased respiratory rate, approaching State 3, and no respiratory inhibition. The enhanced respiration was inhibited by oligomycin. There were no differences in lead effects associated with age, two weeks vs adult, or with brain region. cerebral vs cerebellar. We conclude that there is an energydependent transport of inorganic lead in brain mitochondria. Low concentrations of lead inhibit oxidative phosphorylation with NAD-linked substrates but not with succinate. These in vitro lead effects are similar to those seen in cerebellar mitochondria from lead-treated imnature rats (Holtzman and Hsu. Pediat. Res. 10:70-75. 1976). However, this in-vitro mitochondrial effect does not show the age and re-pecificity seen in lead encephalopathy in the rat and the human. 14 A M M O N I A P R O D U C T I O N BY T H E P R E G N A N T S H E E

No abstract

No abstract