Erythrocyte ALAD

Increases in ALAS activity have been observed in lead workers (Meredith et al. 1978). Leukocyte ALAS was stimulated at a PbB level of 87 pg/dL (Meredith et al. 1978), a level at which ALAD activity is already significantly inhibited. ALAD activity correlated inversely with PbB levels in occupationally exposed individuals (Alessio et al. 1976 Wada et al. 1973), as has been seen in subjects with no occupational exposure (Secchi et al. 1974). Erythrocyte ALAD and hepatic ALAD activities were correlated directly with each other and correlated inversely with PbB levels in the range of 12-56 pg/dL (Secchi etal. 1974). 

M (decreased erythrocyte ALAD activity increase urinary coproporphyrins)... 

Rat (Wistar) Gd 1-21 ad lib (W) 0.45 (decreased erythrocyte ALAD activity in pups lower fetal weights) Hayashi 1983 PbAc... 

Alterations in the heme biosynthetic pathway noted after 7 days. Erythrocyte ALAD activity was depressed and did not recover until 5 weeks after termination of lead treatments No effect on gastric contractions or egestion of pellets of undigested materials No effect on frequency or timing of pellet egestion... 

Decreased number of spermatocytes increase in spermatogonial cysts Erythrocyte ALAD inhibition Anemia reduced blood ALAD activity Reduced stamina ALAD depression, 74%... 

Erythrocytic ALAD Weeks Activity inhibited by lead but also by other metals, (e.g., methylmercury and by ethanol intoxication)... 

Inhibition of erythrocyte ALAD activity Urban population No apparent BLL threshold Negative correlation between BLL and ALAD activity y 2.3-0.18x r =-0.83. Early biochemical evidence of toxicity. Hemberg and Nikkanen 1970... 

Genetically linked deficiencies of erythrocyte ALAD in human subjects have been described by a number of investigators (Bird et al. 1979 Doss and Muller 1982 Benkmann et al. 1983 Astrin et al. 1987 Wetmur et al. 1991). In normal individuals, ALAD activity is sufficiently high, even under conditions of moderate lead toxicity, to sustain heme biosynthesis without the prospect of clinical effects related to heme deficiency. In contrast, when ALAD levels are significantly reduced due to an inherited deficiency of this enzyme, affected individuals could be at greater risk of lead toxicity related... 

Bowers et al. 1992) have shown that the levels of total coproporphyrin in either spot urine samples or 24-h collections fall within a relatively well defined range (Table 1). In view of the sensitivity and magnitude of the coproporphyrin response to lead exposure as demonstrated from animal as well as human studies, it is likely that values exceeding the normal range could be readily detected among lead-exposed subjects if employed in populations in which the normal intra- and interindividual variability is first well defined. Under these circumstances the sensitivity of urinary coproporphyrin may equal or exceed that of erythrocyte ALAD as a measure of low level lead exposure. 

ALA = 5-aminolevulinic acid ALAD = 6-aminolevulinic acid dehydratase ALAS = 5-aminolevulinic acid synthase EP = erythrocyte protoporphyrins FEP = free erythrocyte protoporphyrins FSH = follicle stimulating hormone IQ = intelligence quotient LH = luteinizing hormone NS = not specified (occup) = occupational Py-5 -N = pyrimidine-5-nucleotidase TSH = thyroid stimulating hormone ZPP = erythrocyte protoporphyrin... 

Effects at even lower external and internal exposure levels were reported by Hayashi (1983). Lead acetate at 0.7 mg lead/kg/day in the drinking water of rats for the first 18 or 21 days of pregnancy resulted in decreased ALAD activity in the fetal and maternal erythrocytes and increased ALAD activity in fetal but not maternal liver. Fetal, but not maternal, hematocrits and hemoglobin levels were decreased in the group treated for 21 days. Fetal PbB levels were 27 pg/dL and 19 pg/dL in the 18-day and the 21-day treated groups, respectively. Maternal PbB levels were approximately 4 pg/dL in treated and control groups. The study is limited by the use of one dose level, which precluded assessment of dose response. 

ALA in plasma was as good a discriminator of lead exposure as ALAD activity in workers at PbB levels between 10 and 40 pg/dL and continued to discriminate up to PbB levels approaching 100 pg/dL (Sakai and Morita 1996). The same group of investigators recently showed that the activity of adenine dinucleotide synthetase (NADS) in erythrocytes is a better predictor of PbB levels >40 pg/dL than ALAD (Morita et al. 1997). The decrease in NADS activity between PbB concentration of 5 and 80 pg/dL was linear with a correlation coefficient of -0.87. 

There is no clinical disease state that is pathognomonic for lead exposure. The neurotoxic effects and hematopoietic effects of lead are well recognized. The primary biomarkers of effect for lead are EP, ALAD, basophilic stippling and premature erythrocyte hemolysis, and presence of intranuclear lead inclusion bodies in the kidneys. Of these, activity of ALAD is a sensitive indicator of lead exposure (Hemberg et al. 1970 Morris et al. 1988 Somashekaraiah et al. 1990 Tola et al. 1973), but the assay can not distinguish between moderate and severe exposure (Graziano 1994). Sensitive, reliable, well-established methods exist to monitor for these biomarkers however, they are not specific for lead exposure. Therefore, there is a need to develop more specific biomarkers of effect for lead. Recent data... 

ALAD depression, 86% anemia basophilic stippling of erythrocytes... 

Burns CB, Godwin IR. 1991. A comparison of the effects of inorganic and alkyllead compounds on human erythrocytic delta-aminolevulinic-acid dehydratase (ALAD) activity in vitro. J Appl Toxicol 11 103-111. 

Beegdahl 1A, Geubb A, Schutz A, Desnick RJ, Wetmue JG, Sassa S and Skeeeving S (1997). Lead-binding to d-aminolevulinic acid dehydratase (ALAD) in human erythrocytes. Pharmacol Toxicol 81 153-158. 

Sn(II) ions inhibit erythrocyte 5-aminolevu-linate dehydratase (ALAD) (as do Pb(II) ions), but Sn(IV) ions are without effect on this enzyme. 

Rainbo v trout exposed to supernatant waste developed general stress symptoms at 13-15 °C, and plasma hypocalcemia and sex-dependent inhibition of erythrocytic delta-aminolevulinic acid dehydratase (ALAD) enzyme activity at 7-8°C (Lehtinen etal. 1984). 

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