Palmitoyl protein thioesterase

Infantile neuronal ceroid lipofuscinosis CNL1 Palmitoyl protein thioesterase Saposins... 

The neuronal ceroid lipofuscinoses (CLN), also referred to as Batten s disease, are a group of disorders characterized by the accumulation of autofluorescent lipopigments. Clinical hallmarks include blindness, seizures, cognitive and motor decline and early death. Age of onset varies from infancy to adulthood. Eight genetic forms have been identified [4]. Two involve lysosomal acid hydrolases. CLN1 codes for palmitoyl protein thioesterase 1. Clinically it presents most often in infancy and leads to loss of active movement and visual contact by 3 years of age. It is most common in Finland, where its incidence is 1 20,000. CLN2 codes for a lysosomal pepstatin-insensitive acid protease. 

Lukacs Z, Santavuori P, Keil A, Steinfeld R, Kohlschiitter A (2003) Rapid and simple assay for the determination of tripeptidyl peptidase and palmitoyl protein thioesterase activities in dried blood spots. Clin Chem 49 509-511... 

Data from Verkruyse et al. (1997). Intracellular palmitoyl-protein thioesterase (PPT) was determined using whole cell lysates and anti-PPT antibody. PPT protein in the medium (extracellular) was detected following partial purification to enrich for PPT prior to immunoblotting with anti-PPT antibody. 

Terman A, Neuzil J, Kagedal K, et al. Decreased apoptotic response of inclusion-cell disease fibroblasts a consequence of lysosomal enzyme missorting Exp Cell Res 274 9-15,2002. Verkruyse LA, Natowicz MR, Hofmann SL Palmitoyl-protein thioesterase deficiency in fibroblasts of individuals with infantile neuronal ceroid lipofuscinosis and I-cell disease. Biochim Blophys Acta 1361 1-5,1997. von Figura K, Hasilik A Lysosomal enzymes mind their receptors. Anna Rev Biochem 55 167-193, 1986. 

Palmitoylated proteins Infantile neuronal ceroid lipofuscinosis (NCL) Palmitoyl-protein thioesterase lp32... 

Goswami, R., Ahmed, M., Kilkus, J., Han, T., Dawson, S. A., and Dawson, G. Differential regulation of ceramide in lipid-rich microdomains (rafts) Antagonistic role of palmitoyl -protein thioesterase and neutral sphingomyelinase 2. J Neurosci Res 81 (2005) 208-217. 

Of the deficits unrelated to the glycolipids which show an abundant clinical literature but less interest manifested by scientists in the field of lipidomics are ceroid lipofuscinosis (the deficiency in palmitoyl-protein thioesterase (PPT)) and the Sjogren-Larsson syndrome, a defect of ALDH3A2 gene which encodes fatty aldehyde dehydrogenase (FALDH). It is pertinent to question the reason for such differences between clinical and basic scientific interests reflected in literature citations. 

Ceroid Lipofucinosis palmitoyl-protein thioesterase (PPT 1) granular osmiophilic deposits of acylated proteins CNLl (for PPTl) CNLx>10 1 12500 fluorimetric enzyme assay of PPT... 

The condition is caused by deficiencies of palmitoyl protein thioesterase 1 (PPTl) (or tripeptidyl peptidase 1 (TPPl) and possibly other enzymes resulting in the same clinical presentation of NCL (for Aeural Ceroid Lipofuscinose)). PPTl cleaves long-chain fatty acids from S-acylated proteins within the lyso-some (Lu et al., 1996). How the loss of this activity causes the death of central nervous system neurons is not known. 

The two subtypes of NCLs are due to deficiencies either in the palmitoyl protein thioesterase 1 (PPTl) protein or in the tripeptidyl peptidase 1 (TPPl) protein. The trial aforementioned by a cell therapy was comprised of neural stem/progenitor cells which constitutively synthesize and secrete both the PPTl and TPPl enzymes. In culture, these secreted enzymes are internalized by... 

Lu J.Y., Verkruyse L.A., Hofmann S.L., Lipid thioesters derived from acylated proteins accumulate in infantile neuronal ceroid lipofuscinosis correction of the defect in lymphoblasts by recombinant palmitoyl-protein thioesterase. Proceedings of the National Academy of Sciences of the United States of America 93 (1996) 10046-10050. 

Young E.P., Worthington V.C., Jackson M., Winchester B.G., Pre- and postnatal diagnosis of patients with CLNl and CLN2 by assay of palmitoyl-protein thioesterase and tripeptidyl-peptidase I activities, European Journal of Paediatric Neurology 5 Suppl A (2001) 193-196. 

Infantile neuronal ceroid Palmitoyl protein thioesterase 1 0.013 live births [17,18]... 

S-Palmitoy lation Palmitoyl Protein Thioesterases (PPT) Side chain of Cys Yes Intracellular plasma membrane. Vesicle H-Ras, Gsa... 

Fig. 22.2. Lysosomal catabolism of membrane-associated/ hydrophobic proteins. In infantile neuronal ceroid lipofuscinosis (CLNl) palmitoyl protein thioesterase is deficient (22.4.1). Late infantile neuronal lipofuscinosis (CLN2) is due to a defect in tripeptidyl peptidase I (22.4.2). Sub C = subunit C of ATP synthase complex. CLN3 protein = membrane protein of unknown function. It probably contributes to the disposal of organella membranes, it is defective in juvenile neuronal ceroid lipofuscinosis (CLN3, 22.4.3)...

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