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By Bernard L. Horecker, Earl R. Stadtman

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VIII. The Role of Cell and Tissue Inhibitors B e c a u s e of the large n u m b e r of inhibitors n o w k n o w n to a c c o m p a n y tissue p r o t e i n a s e s , it s e e m s likely that the inhibitors play a significant physiological role. Clues to their function may be gained by selectively measuring the c o n c e n t r a t i o n s of proteinases and their inhibitors u n d e r various normal and pathological conditions. Situations such as uterine growth and involution or m u s c u l a r d y s t r o p h y , in which an organ under­ goes restructuring or inappropriate proteolysis, will be of particular in­ terest.

5 - 7 . 5 , cathepsin B also h y d r o l y z e s proteoglycan, a n o t h e r important constituent of c o n n e c t i v e tissues (101). During p h a g o c y t o s i s , inflamma­ tion, and cell d e a t h , lysosomal e n z y m e s are released into extracellular s p a c e s . H e r e it s e e m s that the cysteine proteinases display at least s o m e activity. Although cathepsins B , H , and L h a v e optimal activity in cleav­ ing proteins at p H 5 - 6 , they h a v e significant activity at p H 7 (72).

T h e r e ­ fore, the low-molecular-weight inhibitors are probably intracellular in lo­ calization. In fact, t w o single-cell p r e p a r a t i o n s , e r y t h r o c y t e s and alveolar m a c r o p h a g e s , b o t h contained I and I . Inhibitors of liver cathepsins B and H w e r e also found in p r o t o z o a and in the organs of the chicken, tuna fish, and t o a d . 4 for 10 minutes at 80°C and purified by passage through a S e p h a d e x G-75 column. T h e n the fractions containing I and I w e r e c h r o m a t o g r a p h e d twice on a C M Bio-Gel A c o l u m n .

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