Porphobilinogen synthase

Chisolm JJ, Thomas DJ, Hamill TG. 1985. Erythrocyte porphobilinogen synthase activity as an indicator of lead exposure to children. Clin Chem 31 601-605. 

Finally, in this last group, we include lead that causes saturnism7, particularly among young children in socially deprived inner cities. The toxicity of environmental Pb finds its molecular explanation in the extraordinary high affinity of Pb (binding constant of 1015 M) for the key Zn-dependent enzyme of haem biosynthesis, porphobilinogen synthase. 

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. 

EXDVXXGXPPAA Delta-aminolevulinic acid dehydratase, chloroplast precursor (porphobilinogen synthase) (ALADH) (ALAD)/ 60-94 Selaginella martensii 100% 0.05... 

Aminolevulinate now leaves the mitochondria. In the cytoplasm, two molecules condense to form porphobilinogen, a compound that already contains the pyrrole ring. Porphobilinogen synthase is inhibited by lead ions. This is why acute lead poisoning is associated with increased concentrations of ALA in the blood and urine. 

Porphobilinogen synthase Urocanate hydratase 3-Hydroxypalmitoyl-[ACP] dehydratase Uroporphyrinogen 111 synthase... 

This enzyme [EC 4.2.1.24], also known as porphobilinogen synthase, catalyzes the reaction of two molecules of... 

In plants, algae and many bacteria there is an alternative route for ALA synthesis that involves the conversion of the intact five-carbon skeleton of glutamate in a series of three steps to yield ALA. In all organisms, two molecules of ALA then condense to form porphobilinogen in a reaction catalyzed by ALA dehydratase (also called porphobilinogen synthase) (Fig. 2a). Inhibition of this enzyme by lead is one of the major manifestations of acute lead poisoning. 

Subsequent reactions occur in the cytoplasm and they are irreversible. Two molecules of 8-aminolevulinate are condensed by the enzyme porphobilinogen synthase to form the trisubstituted pyrrole porphobilinogen. Two enzymes, uroporphyrinogen synthase and uroporphyrinogen cosynthase, condense four molecules of porphobilinogen to the porphyrin uroporphyrinogen III. 

Frankenberg N, Erskine PT, Cooper JB, Shoolingin-Jordan PM, Jahn D, Heinz DW. High resolution crystal structure of a Mg2- —dependent porphobilinogen synthase. J. Mol. Biol. 1999 289 591-602. 

Porphobilinogen synthase defect PS Porphobilinogen synthase autosomal recessive... 

Fabiano, E., Golding, B. T. On the mechanism of pyrrole formation in the Knorr pyrrole synthesis and by porphobilinogen synthase. J. Chem. Soc., Perkin Trans. 11991, 3371-3375. 

ALAD (also known as porphobilinogen synthase) is a cytoplasmic enzyme that catalyzes the formation of the mono-pyrrole porphobilinogen (PEG) from two molecules of ALA with elimination of two molecules of water. The enzyme requires zinc ions as a cofactor and reduced sulfhydryl groups at the active site and is therefore susceptible to inhibition by lead. 

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