Evidence of increased synthesis of delta-aminolevulinic acid dehydratase in experimental lead-poisoned rats.
delta-Aminolevulinic acid dehydratase (porphobilinogen synthase; 5-aminolevulinate hydro-lyase, EC 4.2.1.24) was purified from rat and rabbit erythrocytes to a homogeneous state. Specific activities were 26.0 and 26.6 units/mg protein for the rat and rabbit enzymes, respectively, and their estimated molecular weight was 280000, each consisting of 8 subunits of Mr 35000. In order to quantitate rat delta-aminolevulinic acid dehydratase at several stages of lead-poisoning, a radioimmunoassay technique using goat antiserum against the rat enzyme was developed for the first time. This technique was specific, reproducible and highly sensitive allowing determination of 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. On the contrary, the restored enzyme activity, assayed in the presence of Zn2+ and dithiothreitol, was greater than normal by the fourth day of lead administration in bone-marrow cells and by the ninth day in the peripheral blood. The increased activity level stayed the same from the ninth day onward. The enzyme content as determined directly by the radioimmunoassay technique at this stage was about 2-fold above that the control. There was no significant difference in the number of reticulocytes and the distribution profile of different types of reticulocytes between the lead-exposed and non-exposed rats. Therefore, the increase in the amount of delta-aminolevulinic acid dehydratase in erythrocytes of lead-poisoned rats was suggested to be due to an increased rate of synthesis in the bone-marrow cells.
D000818:Animals; D001853:Bone Marrow / Q000201:enzymology; D001854:Bone Marrow Cells; D004906:Erythrocyte Count; D004912:Erythrocytes / Q000201:enzymology*; D007855:Lead Poisoning / Q000201:enzymology*; D046911:Macromolecular Substances; D008970:Molecular Weight; D000623:Porphobilinogen Synthase / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D012156:Reticulocytes / Q000166:cytology
D046911:Macromolecular Substances; D000623:Porphobilinogen Synthase