Tripeptidyl-peptidase I deficiency in classical late-infantile neuronal ceroid lipofuscinosis brain tissue. Evidence for defective peptidase rather than proteinase activity
Mj. Warburton et F. Bernardini, Tripeptidyl-peptidase I deficiency in classical late-infantile neuronal ceroid lipofuscinosis brain tissue. Evidence for defective peptidase rather than proteinase activity, J INH MET D, 23(2), 2000, pp. 145-154
Brain tissue from patients with classical late-infantile neuronal ceroid li
pofuscinosis (LINCL, an infantile form of Batten disease) is deficient in t
he lysosomal enzyme tripeptidyl-peptidase I (EC 3.4.14.9). The activities o
f other lysosomal enzymes are either increased or decreased. Tripeptidyl-pe
ptidase I is a pepstatin-insensitive exo-tripeptidase, with little or no en
do-proteolytic activity, that is active on small peptides but not on large
proteins. Using haemoglobin and casein as substrates for proteolytic activi
ty, we were unable to demonstrate any significant defect in pepstatin-sensi
tive or pepstatin-insensitive proteinase activity in brain tissue or cultur
ed skin fibroblasts of LINCL patients. These observations suggest that the
lysosomal storage of undegraded, small peptides in LINCL results from the a
bsence of peptidase rather than proteinase activity.