Tripeptidyl-peptidase I deficiency in classical late-infantile neuronal ceroid lipofuscinosis brain tissue. Evidence for defective peptidase rather than proteinase activity

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.