5-aminolaevulinate dehydratase

Aminolaevulinate dehydratase (ALA-D) (EC 4.2.1.24) in mice and rats livers was determined after 7-fold administration of the studied compounds according to Berlin (ref. 17), as modified by Schlick et al. (ref. 18). 5-Aminolaevulinate synthase (ALA-S) (EC 2.3.1.37) was also assayed in the liver according to Sassa and Granick (ref. 19). 

Figure 12.8 Some other active-site coordination motifs in mononuclear zinc enzymes from left to right bacteriophage T7 lysozyme, 5-aminolaevulinate dehydratase, Ada DNA repair protein. (Reprinted with permission from Parkin, 2004. Copyright (2004) American Chemical Society.)...

The 5-aminolaevulinate dehydratase (or porphobilinogen synthase), which catalyses the condensation of two molecules of 5-aminolaevulinate to form the pyrrole precursor of the porphyrins (haem, chlorophyll, cobalamines), has the motif [(Cys)3 Zn2+-OH2]. As pointed out earlier (see Chapter 1), this enzyme is the target for saturnism, the Pb toxicity frequently observed among inner city children. 

Fig. 39. The last step of the 8-aminolaevulinate dehydratase reaction takes place stercospccifically...

Kaya AH, Plewinska M, Wong DM, Desnick RJ, Wetmur JG. Human delta-aminolaevulinate dehydratase (ALAD) gene structure and alternative splicing of the erythroid and housekeeping mRNAs. Genomics 1994 19 242-8. 

Schaller, KH. Berlin, A. A-Aminolaevulinate Dehydratase. In Methods of Enzymatic Analysis (Volume IV, Third Edition). Bergmeyer, HU, Editor-in-Chief Bergmeyer, J Grapi, M eds. Weinheim Verlag Chemie GmbH, 1984 363-368. 

Section M Smil, V. (1997) Global population and the nitrogen cycle. Sci. Amer. 277(7), 58-63. Warren, M.J., Cooper, J.B., Wood, S.P. and Shoolingan-Jordan, P.M. (1998) Lead poisoning, haem synthesis and 5-aminolaevulinic acid dehydratase. Trends Biochem. Sci. 23, 217-221. Warren, M.J. and Scott, A.I. (1990) Tetrapyrrole assembly and modification into the ligands of biologically functional cofactors. Trends Biochem. Sci. 15, 486-491. 

The inhibition of chlorophyll biosynthesis by metals was described for higher plants (Bazinsky et al., 1980 Prassad and Prassad, 1987) as well as for algae (De Filippis and Pallaghy, 1976 De Filippis et al., 1981 a). Sensitivity to metals was found for two enzymes of this pathway 8-aminolaevulinic acid (ALA)-dehydratase (EC 4.2.1.24) and protochlorophyllide reductase. Stobart et al. (1985) reported that the synthesis of 8-ALA is also an important site of inhibition in barley (Hordeum vulgare). 

Lead Lead poisoning (= saturnism) results in mild, rapidly regressive toxic hepatitis in about 30% of cases. Occasionally, eosinophilic, acid-resistant inclusions are found in the nuclei of the liver cells (so-called lead protein complexes). Steatosis and liver-cell necrosis have also been witnessed. Although there is a correlation between exposure to lead and severity of damage, individual sensitivity to lead can nevertheless vary. In addition, lead intoxication causes an inhibition of erythrocyte 5-aminolaevulinic acid dehydratase and an induction of 5-aminolaevulinic acid synthase. This brings about the manifestation of acute intermittent porphyria. (8)... 

Doss porphyria DP Aminolaevulinic acid dehydratase autosomal recessive... 

Sassa S. 6-aminolaevulinic acid dehydratase assay. Enzyme 1982 28 133-45. 

Sieg T, Doss MO, Kandels H, Schneider J. Effect of alcohol on 5-aminolaevulinic acid dehydratase and porphyrin metabolism in man. Clin Chim Acta 1991 202 211-8. 

Sithisarankul P, Schwartz BS, Lee BK, Kelsey KT, Strickland PT. Aminolevulinate dehydratase genotype mediates plasma levels of the neurotoxin, 5-aminolaevulinic acid, in lead exposed workers. Am J Ind Med 1997 32 15-20. 

Chalevelakis G, Bouronikou H, Yalouris AG, Economopoulos T, AthanaseHs S, Raptis S. Delta-Aminolaevulinic acid dehydratase as an index of lead toxicity Time for a reappraisal Eur J Clin Invest 1995 25 53-8. 

Barlow, J. J., Baruah, J. K. and Davison, A. N. (1977). D-Aminolaevulinic acid dehydratase activity and focal brain haemorrhages in lead-treated rats. Acta Neuropathol. (Berlin), 39, 219... 

The best documented effects of lead on blood are its interference with the biosynthesis of haem, which is essential for the production of haemoglobin (the red oxygen-carrying pigment in red blood cells). The two most important points of interference are the formation of the enzyme 6-aminolaevulinic acid dehydratase (6-ALAD) and the insertion of iron into protoporphyrin [6]. 

Meredith PA, Moore MA, Goldberg A (1977) Effects of aluminium, lead and zinc on delta-aminolaevulinic acid dehydratase. Enzyme 22 22-27 Mertz LM, Horn VJ, Baum BJ, Ambudkar IS (1990) Calcium entry in rat parotid acini activation by carbachol and aluminum fluroride. Am J Physiol 258 C654-C661... 

The enzyme which converts 6-aminolaevulinic acid to porphobilinogen. Decreased red cell 6-aminolaevulinic acid dehydratase activity is found in cases of lead poisoning. 

Decreased erythrocyte 6-aminolaevulinic acid dehydratase activity. 

Lead can also be measured indirectly in blood by means of its inhibition of the activity of an enxyme, aminolaevulinic acid dehydratase (ALAD), which is involved in the haem synthesis pathway. ALAD is inhibited in an exponential fashion at blood levels from between 5 and lO/rg/dl upwards (Berlin and Schaller, 1974). 

When referring to the early or subcriticaL effects of lead in humans as biological indicators of exposure, the primary concern is the alterations in those levels of intermediates in the haem biosynthesis pathway that are known to be affected by the presence of lead. Three processes that have lent themselves to examination in the context of biological monitoring include (1) the inhibition of delta-aminolaevulinic acid dehydratase (5-ALA-D) ... 

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