(601ab) Analysis of Kinetics of Elastase Inhibition VIA the M1 Form of α-1-Antitrypsin

Alpha-1-Antitrypsin (A1AT) Deficiency (A1AD) is a potentially debilitating condition that causes the early onset of emphysema in the third or fourth decade of life.  It is an inherited condition that is estimated to affect more than 1.1 million people worldwide, and approximately 116 million people are carriers of one or more of the associated genetic mutations that can be passed to their offspring.  The diagnosis of A1AD often occurs only after extended periods of time and with repeated visits to a physician.  Further, the condition is largely under-diagnosed with as few as 10% of those in the USA with this condition actually being diagnosed.  While no cure exists, it has been shown that treatment prior to the onset of emphysema of a deficient patient can drastically slow the onset of A1AD.  Testing for this condition typically does not occur until after emphysema has presented.  To develop methodology for improved diagnostic platforms, the kinetics of interaction between A1AT and Porcine Pancreatic Elastase (PPE) has been examined as a possible route through which testing can be done. With this work, Michaelis-Menten kinetics has been applied for the first time to this system and found to describe the kinetics of A1AT as a non-competitive inhibitor.  Such efforts are a part of an ongoing process to improve diagnosis for A1AD.