Enzymes as Factors in Resistance to Tuberculosis

Jobling and Petersen10 presented evidence as long ago as 1914 that the lipoids of tubercle bacilli inhibit proteolytic enzymes. More recently, Peck"5 has shown that these lipoids also inhibit crystallized trypsin and that the higher the molecular weight of the lipoid the greater is its interference with the enzyme function. Further investigation involving fractions of tubercle bacilli and enzyme activity has been reported from this laboratory.8 It has been shown that lecithinase, one of two enzymes essential for the cleavage of tubercle phosphatide, is strikingly inhibited by fatty acids split off from the phosphatide, which is one of the most potent components of the tubercle bacillus (Sabin"7). This adverse effect of fatty acids varies with enzymes derived from different species or different organs of the same species, and correlates with the ability of different organs to split tubercle phosphatide. These facts supplement the finding that enzyme activity, as determined on model substrates, does not necessarily indicate the effect of the enzyme on tubercle phosphatide. Several problems present themselves. As will be shown, the difference in the response of the enzymes is not due to substances incidentally present in the enzyme test solutions. This made it desirable to determine how the lipoids affect the enzyme. The mechanism of inhibition or inactivation effected by lipoids has been considered of practical importance and has been investigated (Peck," Stock and Francis"8). The problem whether molecular weight or chemical structure of the fatty acids or changes they exert on surface tensions are the factors that determine inhibition and its extent was studied with reference to lecithinase.