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Evidence of increased synthesis of delta amino levulinic acid dehydratase ec 4.2.1.24 in experimental lead poisoned rats


, : Evidence of increased synthesis of delta amino levulinic acid dehydratase ec 4.2.1.24 in experimental lead poisoned rats. Biochimica et Biophysica Acta 678(1): 39-50

.delta.-Aminolevulinic acid dehydratase (porphobilinogen synthase; 5-aminolevulinate hydrolyase, EC 4.2.1.24) was purified from rat and rabbit erythrocytes to a homogeneous state. Specific activities were 26.0 and 26.6 U/mg protein for the rat and rabbit enzymes, respectively, and their estimated MW was 280,000, each consisting of 8 subunits of MW 35,000. In order to quantitate rat .delta.-aminolevulinic acid dehydratase at several stages of Pb-poisoning, a radioimmunoassay technique using goat antiserum against the rat enzyme was developed. This technique was specific, reproducible and highly sensitive allowing determination of 1 ng enzyme. When drinking water containing 25 mM lead acetate was given daily to rats ad lib the .delta.-aminolevulinic acid dehydratase activity in the blood, assayed without any pretreatment, decreased to 8% of the control level on the next day. The restored enzyme activity, assayed in the presence of Zn2+ and dithiothreitol, was greater than normal by the 4th day of Pb administration in bone marrow cells and by the 9th day in peripheral blood. The increased activity level stayed the same from the 9th day onward. The enzyme content as determined directly by the radioimmunoassay technique at this stage was .apprx. 2-fold above control. There was no significant difference in the number of reticulocytes and the distribution profile of different types of reticulocytes between Pb-exposed and non-exposed rats. Increased .delta.-aminolevulinic acid dehydratase in erythrocytes of Pb-poisoned rats was probably due to an increased rate of synthesis in bone marrow cells.

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