S-Aminolevulinic acid dehydratase

Lead-induced anemia results from impairment of heme biosynthesis and acceleration of red blood cell destmction (10,13). Lead-induced inhibition of heme biosynthesis is caused by inhibition of S-aminolevulinic acid dehydratase and ferrochelatase which starts to occur at blood lead levels of 10 to 20 pu gjdL and 25 to 30 //g/dL, respectively (10,13). Anemia, however, is not manifested until higher levels are reached. 

Schmitt, C.J., F.J. Dwyer, and S.E. Finger. 1984. Bioavailability of Pb and Zn from mine tailings as indicated by erythrocyte S-aminolevulinic acid dehydratase (ALA-D) activity in suckers (pisces catostomidae). Canad. Jour. Fish. Aquat. Sci. 41 1030-1040. 

Figure 3 The synthesis of heme from glycine and sucdnyl-CoA. The enzymes are ALAS, S-aminolevulinic acid (ALA) synthase ALAD, S-aminolevulinic acid dehydratase PBGD, porphobilinogen deaminase UROIIIS, uroporphyrinogen III synthase UROD, uroporphyrinogen decarboxylase CPO, coproporphyrinogen oxidase PPO, protoporphyrinogen oxidase and FECH, ferrochelatase.

Marks GS (1985) Exposure to toxic agents the heme biosynthetic pathway and hemoproteins as indicator. Crit Rev Toxicol 15 151-179 Martinez G, Cebrian M, Chamorro G, Jauge P (1983) Urinary uroporphyrin as an indicator of arsenic exposure in rats. Proc West Pharmacol Soc 26 171 Mayo Medical Laboratories Interpretive Handbood (1990) Mayo Medical Laboratories, Rochester, MN, pp 149-152 Meredith PA, Moore MR, Goldberg A (1974) The effects of aluminum, lead and zinc on ( -aminolevulinic acid dehydratase. Biochem Soc Trans 2 1243-1245 Millar JA, Gumming RL, Battistini V, Cabswell F, Goldberg A (1970) Lead and S-aminolevulinic acid dehydratase levels in mentally retarded children and in lead-poisoned suckling rats. Lancet ii 695-698... 

ALAD = aminolevulinic acid dehydratase d = day(s) F = female Gd = gestational day Hemato = hematological hr = hour(s) LDH = lactatate dehydrogenase LOAEL = lowest-observable-adverse-effect level M = male NOAEL = no-observable-adverse-effect level Resp = respiratory wk = week(s). 

Kuhnert PM, Erhard P, Kuhnert BR. 1977. Lead and delta-aminolevulinic acid dehydratase in RBC s of urban mothers and fetuses. Environ Res 14 73-80. 

Castrale, J.S. and M. Oster. 1993. Lead and delta-aminolevulinic acid dehydratase in the blood of mourning doves dosed with lead shot. Proc. Indiana Acad. Sci. 102 265-272. 

Vogiatzis, A.K. and Loumbourdis, N.S. Exposure of Rana ridibunda to lead. I. Study of lead accumulation in various tissues and hepatic k-aminolevulinic acid dehydratase activity, / Appl. Toxicol, 19(l) 25-29, 1999. 

NT386 Kaul, K., and P. S. Sabbarwal. Kine-tin induced changes in delta-aminolevulinic acid dehydratase of tobacco callus. Plant Physiol 174 54 644. NT398... 

Byung-Kook L, Lee G-S, Stewert WF, Kyu-Dong A, Simon D, Kelsey KT,Todd AC, Schwartz BS. Associations of blood pressure and hypertension with lead dose measures and polymorphisms in the vitamin D receptor and p-aminolevulinic acid dehydratase genes. Environ Health Perspectives 2001 109 383-389. 

Sassa S, Kappas A. Hereditary tyrosinemia and the heme biosynthetic pathway profound inhibition of delta-aminolevulinic acid dehydratase activity by suc-cinylacetone. J Clin Invest 1983 71 625-34. 

Genetic Glucose-6-phosphate dehydrogenase deficiency, glutathione deficiency, glutathione reductase deficiency, thalassemia, tyrosinemia, Wilson s disease, 6-aminolevulinic acid dehydratase deficiency... 

Goering PL and Rehm S (1990) Inhibition of liver, kidney, and erythrocyte aminolevulinic acid dehydratase (porphobilinogen synthase) by gallium in the rat. Environ Res 53 135-151. 

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. 

Schutz a and Skerfving S (1976) Effect of a short, heavy exposure to lead dust upon blood lead level, erythrocyte d-aminolevulinic acid dehydratase activity and urinary excretion lead, d-aminolevu-linic acid, and coproporphyrine. Scand J Work Environ Health 1 54-59. 

Lee, S.S., B.K. Lee, G.S. Lee, W.F. Stewart, D. Simon, K. Kelsey, A.C. Todd, and B.S. Schwartz. 2001b. Associations of lead biomarkers and delta-aminolevulinic acid dehydratase and vitamin D receptor genotypes with hematopoietic outcomes in Korean lead workers. Scand. J. Work Environ. Health 27(6) 402-411. 

Sithisarankul, P., B.S. Schwartz, B.K. Lee, K.T. Kelsey, and P.T. Strickland. 1997. Aminolevulinic acid dehydratase genotype mediates plasma levels of the neurotoxin, 5-aminolevulinic acid, in lead-exposed workers. Am. J. Ind. Med. 32(1) 15-20. 

Weaver, V.M., B.K. Lee, A.C. Todd, K.D. Ahn, W. Shi, B.G. Jaar, K.T. Kelsey, M.E. Lustberg, E.K. Silbergeld, P.J. Parsons, J. Wen, and B.S. Schwartz. 2006. Effect modification by delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase gene polymorphisms on associations between patella lead and renal function in lead workers. Environ. Res. 102(l) 61-69. 

Alexander, B.H., Checkoway, H., Costa-Mallen, P., Faustman, E.M., Woods, J.S., Kelsey, K.T., et al., 1998. Interaction of blood lead and 6-aminolevulinic acid dehydratase genotype on markers of heme synthesis and sperm production in lead smelter workers. Environ. Health Perspect. 106, 213-216. 

Bergdahl, I.A., Gerhardsson, L., Schiitz, A., Desnick, R.J., Wetmur, J.G., Skerfving, S., 1997a. Delta-aminolevulinic acid dehydratase polymorphism influence on lead levels and kidney function in humans. Arch. Environ. Health 52, 91—96. 

Schwartz, B.S., Lee, B.-K., Stewart, W., Ahn, K.-D., Springer, K., Kelsey, K., 1995. Associations of 8-aminolevulinic acid dehydratase genotype with plant, exposure duration, and blood lead and zinc protoporphyrin levels in Korean lead workers. Am. J. Epidemiol. 142, 738-745. 

Chia, S.-E., Zhou, H.J., Yap, E., Tham, M.T., Dong, N.-V., Hong Tu, N.T., et al., 2006. Association of renal function and delta -aminolevulinic acid dehydratase polymorphism among Vietnamese and Singapore workers exposed to inorganic lead. Occup. Environ. Med. 63, 180-186. 

Wu, M.T., Kelsey, K., Schwartz, J., Sparrow, D., Weiss, S., Hu, H., 2003. A 6-aminolevulinic acid dehydratase (ALAD) may modify the relationship of low level lead exposure to uricemia and renal function the Normative Aging Study. Environ. Health Perspect. Ill, 335—341. 

Granick, J.L., Sassa, S., Granick, S., Levere, R.D., Kappas, A., 1973. Studies in lead poisoning II. Correlation between the ratio of activated to inactivated 6-aminolevulinic acid dehydratase of whole blood and the whole blood level. Biochem. Med. 8, 149—150. 

Kelada, S.N., Shelton, E., Kaufmann, R.B., Khoury, M.J., 2001. 8-Aminolevulinic acid dehydratase genotype and lead toxicity a HuGE review. Am. J. Epidemiol. 154, 1—13. 

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