A strong correlation between the deficiency of alpha1-antitrypsin (a human serum protein) and emphysema, a chronic obstructive pulmonary disease, exists. The objective of this proposal is to define what possible changes in the biosynthesis and degradation of alpha1-antitrypsin could produce the deficiency of this protein. Structural differences of alpha1- antitrypsin isolated from normal and deficient (emphysemic) individuals will be characterized. Levels of biosynthetic and degradative enzymes will be measured to determine if enzymes produce structural alterations leading to alpha1-antitrypsin deficiency. Alternatively, the physico- chemical difference in alpha1-antitrypsin resulting from a genetic defect may cause decreased transport from liver to serum, decreased stability in serum or faster clearance from the circulatory system. These processes will also be examined as causes for deficiency. By defining the exact cause of deficiency, therapeutic measures to control the deficiency may be possible. Enzyme deficiencies can be treated with specific inhibitors. If physico-chemical structure of alpha1-antitrypsin in emphysemics leads to deficiency, in vivo alterations of protein structure to increase the stability may be feasible.