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In animals, some of bacteria and fungi, and the first step in tetrapyrrole synthesis is the condensation of the amino acid glycine with succinyl CoA (an intermediate of the citric acid cycle) to built ALA (aminolaevulinic acid). This reaction is catalyzed by the enzyme ALA synthase that needed the coenzyme pyridoxal phosphate and is situated in the mitochondria of eukaryotes. This committed phase in the pathway is subject to regulation. Synthesis of the ALA synthase is feedback-inhibited by heme. In algae, plants and various bacteria there is an alternative route for ALA synthesis which have the conversion of the intact five-carbon skeleton of glutamate in a series of three steps to yield ALA. In all organisms there are two molecules of ALA then condensing to form porphobilinogen in a reaction catalyzed by ALA dehydratase (also called as porphobilinogen synthase). Inhibition of this enzyme by lead is one of the main manifestations of acute lead poisoning.
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