Amino levulinic acid dehydratase

Hodson, P.V. 1976. d-amino levulinic acid dehydratase activity of fish blood as an indicator of a harmful exposure to lead. Jour. Fish. Res. Board Can. 33 268-271. 

Permanence of response. Similarly, it is important to know how long the response lasts. If it is transient, it may readily be missed. The inhibition of AChE, especially in blood, is a transient response and thus it is necessary to know when the exposure occurred to assess the importance of the degree of inhibition. In contrast, the inhibition the enzyme amino levulinic acid dehydratase by lead is only slowly reversed. 

At least three polymorphic genes have been identified that potentially can influence the bioaccumulation and toxicokinetics of lead in humans (1) the gene coding for 6-amino-levulinic acid dehydratase (ALAD) (2) the Vitamin D receptor (VDR) gene and (3) HFE, the gene for hereditary hemochromatosis (Onalaja et al. 2000). 

Berlin, A. Schaller, KH. European Standardized Method for the determination of delta-amino-levulinic acid dehydratase activity in blood. Z, Klin, Chem, Klin. Biochem. 1974 12 389-390. 

Louis, E.D., L. Applegate, J.H. Graziano, M. Parides, V. Slavkovich, and H.K. Bhat. 2005. Interaction between blood lead concentration and delta-amino-levulinic acid dehydratase gene polymorphisms increases the odds of essential tremor. Mov. Disord. 20(9) 1170-1177. 

Beside the use of a single enzyme, a cocktail of different biocatalysts can also be used in performing a domino process, provided that the enzymes do not interfere one with another. This approach was used by Scott and coworkers in the synthesis of precorrin-5 (8-61) (Scheme 8.16) [24]. Starting from 6-amino levulinic acid (ALA) 8-60, a mixture of eight different enzymes including the ALA-dehydratase to form porphobilinogen (PBG), as well as PBG deaminase and co-synthetase to furnish the tetracyclic uroporphyrinogen III (8-62) as intermediates, was employed to provide precorrin-5 (8-61) in 30% yield. 

Dec-trans-4-enoic acid, 3-hydroxy-6-iso-pro-pyl-3-methyl-9-oxo, (6S) Lf 0.037 Dec-trans-4-enoic acid, 3-hydroxy-6-iso-pro-pyl-3-methyl-9-oxo Lf 0.008 Dehydratase, A-amino-levulinic acid ... 

Intoxication. This indicates that the absorbed lead is having adverse metabolic effects upon a body tissue. The toxicity is proportional to the concentration of lead at the site. Defining minimal manifestations of toxicity has extended with our increasing ability to develop sensitive indices of toxicity. Inhibition of delta-amino levulinic add dehydratase with an increase in urinary amino-levulinic acid is a relatively sensitive index of toxidty in intoxication, indicating that the lead is having an adverse effect on porphyrin metabolism... 

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