Angiotensin-converting enzyme: immunologic, structural, and developmental aspects.
Immunization of dog and rat high pure rabbit pulmonary angiotensin-converting enzyme elicited, in some individuals, antibodies that inhibited their own converting enzyme. Active immunization with an immunologically related enzyme is thus a plausible approach for developing biologically based inhibitors of enzymes that are either in or accessible to the circulation. Rabbit testicular peptidyldipeptide hydrolase was purified to homogeneity and found to be a considerably smaller (Mr approximately 100,000) glycoprotein than pulmonary converting enzyme (Mr approximately 140,000). The two enzymes differed at their amino- and carboxy-termini. However, they exhibited identical catalytic properties, and antibodies prepared against either inhibited both similarly. In competition radioimmunoassays, antibodies against the pulmonary enzyme preferred it to the testicular species, whereas those against the latter did not distinguish between the two molecules. The testicular isozyme thus resembles an internal part of the pulmonary polypeptide, which includes its active site. In a reticulocyte lysate, mRNA from the lungs of immature and mature rabbits comparably primed the synthesis of a polypeptide (Mr approximately 129,000) that reacted with anticonverting enzyme antibodies. In contrast, an immunoreactive species was programed only by mRNA from the testis of mature animals, and this protein was much smaller (Mr approximately 85,000). Maturation dependence and a shorter polypeptide chain, the regulatory and structural properties that distinguish the testicular isozyme, are thus each pretranslationally determined.
D000818:Animals; D000917:Antibody Formation; D000936:Antigen-Antibody Complex; D004285:Dogs; D010450:Endopeptidases / Q000378:metabolism; D007106:Immune Sera; D007700:Kinetics; D008168:Lung / Q000201:enzymology; D008297:Male; D008970:Molecular Weight; D009928:Organ Specificity; D007703:Peptidyl-Dipeptidase A / Q000276:immunology / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D013379:Substrate Specificity; D013737:Testis / Q000201:enzymology
D000936:Antigen-Antibody Complex; D007106:Immune Sera; D010450:Endopeptidases; C020071:dipeptidyl carboxypeptidase; D007703:Peptidyl-Dipeptidase A