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The lysosomal degradation of ceramide is catalyzed by acid ceramidase and requires sphingolipid activator proteins (SAP) as cofactors in vivo. The aim of this study was to investigate how ceramide is hydrolyzed by acid ceramidase at the water-membrane interface in the presence of sphingolipid activator proteins in a liposomal assay system. The degradation of membrane-bound ceramide was significantly increased both in the absence and presence of SAP-D when anionic lysosomal phospholipids such as bis (monoacylglycero) phosphate, phosphatidylinositol, and dolichol phosphate were incorporated into substrate-bearing liposomes. Higher ceramide degradation rates were observed in vesicles with increased membrane curvature. Dilution assays indicated that acid ceramidase remained bound to the liposomal surface during catalysis. Not only SAP-D, but also SAP-C and SAP-A, were found to be stimulators of ceramide hydrolysis in the presence of anionic phospholipids. This finding was confirmed by cell culture studies, in which SAP-A, -C, and -D reduced the amount of ceramide storage observed in fibroblasts of a patient suffering from prosaposin deficiency. Strong protein-lipid interactions were observed for both SAP-D and acid ceramidase in surface plasmon resonance experiments. Maximum binding of SAP-D and acid ceramidase to lipid bilayers occurred at pH 4. 0. Our results demonstrate that anionic, lysosomal lipids are required for efficient hydrolysis of ceramide by acid ceramidase. The lysosomal degradation of ceramide is catalyzed by acid ceramidase and requires sphingolipid activator proteins (SAP) as cofactors in vivo. The aim of this study was to investigate how ceramide is hydrolyzed by acid ceramidase at the water-membrane interface in the presence of sphingolipid activator proteins in a liposomal assay system. The degradation of membrane-bound ceramide was significantly increased both in the absence and presence of SAP-D when anionic lysosomal phospholipids such as bis (monoacylglycero) phosphate, phosphatidylinositol, and dolichol phosphate were incorporated into substrate-bearing liposomes. Higher ceramide degradation rates were observed in vesicles with increased membrane curvature. Dilution assays indicated that acid ceramidase remained bound to the liposomal surface during catalysis. Not only SAP-D, but also SAP-C and SAP-A, were found to be stimulators of ceramide hydrolysis in the presence of anionic phospholipids. This finding was confirmed by cell culture studies, in which SAP-A, -C, and -D reduced the amount of ceramide storage observed in fibroblasts of a patient suffering from prosaposin deficiency. Strong protein-lipid interactions were observed for both SAP-D and acid ceramidase in surface plasmon resonance experiments. Maximum binding of SAP-D and acid ceramidase to lipid bilayers occurred at pH 4. 0. Our results demonstrate that anionic, lysosomal lipids are required for efficient hydrolysis of ceramide by acid ceramidase. glycosphingolipids sphingolipids acid ceramidase sphingolipid activator proteins bis (monoacylglycero) phosphate phosphatidylinositol cholesterol small unilamellar vesicles large unilamellar vesicles surface plasmon resonance spectroscopy 2-2-hydroxy-1, 1-bis (hydroxymethyl) ethylaminoethanesulfonic acid Glycosphingolipids (GSLs) 1 are characteristic components of the extracytosolic leaflet of the plasma membrane of eukaryotic cells. GSLs are composed of a hydrophilic carbohydrate chain linked to a hydrophobic ceramide moiety. They form cell type-specific patterns on the cell surface, which can change with cell growth, differentiation, viral transformation, or oncogenesis (1Hakamori S. Annu. Rev. Biochem. 1981; 50: 733-764Crossref PubMed Scopus (1462) Google Scholar). Degradation of GSLs takes place in the acidic compartments of the cell, namely endosomes and lysosomes. According to a recent model for the topology of lysosomal digestion, GSLs reach the lysosome after endocytosis from the plasma membrane in the form of intraendosomal and intralysosomal vesicles (2Sandhoff K. Kolter T. Trends Cell Biol. 1996; 6: 98-103Abstract Full Text PDF PubMed Scopus (147) Google Scholar). In the lysosomes, GSLs are degraded by acidic exohydrolases. The final step of GSL catabolism is the hydrolysis of ceramide into sphingosine and fatty acid by acid ceramidase (AC, N-acylsphingosine amidohydrolase, EC3. 5. 1. 23 (3Bernardo K. Hurwitz R. Zenk T. Desnick R. J. Ferlinz K. Schuchmann E. H. Sandhoff K. J. Biol. Chem. 1995; 270: 11098-11102Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar) ). An inherited deficiency of AC activity is the principal cause of Farber disease, a rare, autosomal recessive inherited sphingolipid storage disorder. Farber disease is characterized by a massive accumulation of ceramide in lysosomes of various tissues such as liver, spleen, lung, and heart (4Moser H. W. Scriver C. R. Beaudet A. L. Sly W. L. Valle D. The Metabolic Basis of Inherited Disease. 7th Ed. McGraw Hill Inc. , New York1995: 2589-2599Google Scholar). A total of seven different clinical subtypes of Farber disease have been reported, six of which are believed to be primarily caused by mutations in the AC gene. Farber disease type 7 is the result of a complete lack of sphingolipid activator proteins (SAPs) due to a mutation in the initiation codon of the SAP precursor protein prosaposin and is also known as sphingolipid activator protein deficiency. This deficiency not only affects the degradation of ceramide by AC but also the degradation of other GSLs such as glucosylceramide and galactosylceramide by glucocerebrosidase and galactocerebrosidase, respectively (4Moser H. W. Scriver C. R. Beaudet A. L. Sly W. L. Valle D. The Metabolic Basis of Inherited Disease. 7th Ed. McGraw Hill Inc. , New York1995: 2589-2599Google Scholar). The lysosomal degradation of GSLs with short oligosaccharide head groups requires the coordinate action of both acidic hydrolases and SAPs. SAPs are a group of small, heat-stable, enzymatically inactive glycoproteins. While the GM2 activator protein (GM2-AP) is encoded by its own gene, SAP-A, -B, -C, and -D are derived from a common precursor protein, the SAP precursor or prosaposin, through proteolytic processing (5Fürst W. Sandhoff K. Biochim. Biophys. Acta. 1992; 1126: 1-16Crossref PubMed Scopus (246) Google Scholar). All four SAPs display a high degree of homology such as conserved glycosylation sites, matching patches of hydrophobic amino acid residues, and identical location and connectivity of disulfide bridges (6Ponting C. P. Protein Sci. 1994; 3: 359-361Crossref PubMed Scopus (42) Google Scholar, 7Vaccaro A. M. Salvioli R. Barca A. Tatti M. Ciaffoni F. Maras B. Siciliano R. Zappacosta F. J. Biol. Chem. 1995; 270: 9953-9960Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar, 8Tatti M. Salvioli R. Ciaffoni F. Pucci P. Andolfo A. Amoresanp A. Vaccaro A. M. Eur. J. Biochem. 1999; 263: 486-494Crossref PubMed Scopus (24) Google Scholar). To measure AC activity in vitro, ceramide has to be solubilized in a complex mixture of synthetic nonionic and anionic detergents (3Bernardo K. Hurwitz R. Zenk T. Desnick R. J. Ferlinz K. Schuchmann E. H. Sandhoff K. J. Biol. Chem. 1995; 270: 11098-11102Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar). The efficient hydrolysis of ceramide by AC in vivo requires the presence of SAPs. The requirement of AC for SAP-D was demonstrated by metabolic labeling studies using fibroblasts from a patient suffering from a prosaposin deficiency. Supplementing the cell culture medium with purified SAP-D specifically reduced the ceramide accumulation observed in these cells (9Klein A. Henseler M. Klein C. Suzuki K. Harzer K. Sandhoff K. Biochem. Biophys. Res. Commun. 1994; 200: 1440-1448Crossref PubMed Scopus (127) Google Scholar). However, how SAP-D precisely cooperates with AC to effect this reduction in ceramide storage has not yet been investigated. Furthermore, the mechanism by which water-soluble AC interacts with its membrane-bound substrate ceramide, and how this interaction is modulated by SAPs or by other cofactors, is currently unknown. A number of studies have shown that some lysosomal hydrolases, such as lactosylceramidase, glucocerebrosidase, and acid sphingomyelinase, are stimulated by different acidic phospholipids including phosphatidylserine, phosphatidic acid, phosphatidylinositol (PI), bis (monoacylglycero) phosphate (BMP), and dolichol phosphate (10Zschoche A. Fürst W. Schwarzmann G. Sandhoff K. Eur. J. Biochem. 1994; 222: 83-90Crossref PubMed Scopus (37) Google Scholar, 11Vaccaro A. M. Tatti M. Salvioli R. Ciaffoni F. Gallozzi E. Biochim. Biophys. Acta. 1990; 1033: 73-79Crossref PubMed Scopus (12) Google Scholar, 12Wilkening G. Linke T. Sandhoff K. J. Biol. Chem. 1998; 273: 30271-30278Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar, 13Linke, T. , Wilkening, G. , Lansmann, S. , Moczall, H. , Bartelsen, O. , Weisgerber, J. , and Sandhoff, K. (2000) Biol. Chem. , in Scholar). these lipids only in the acidic compartments of the cell, and its of the total from purified lysosomes, is to be in the of S. J. Biol. Chem. Full Text PDF PubMed Google Scholar, W. Chem. PubMed Scopus Google Scholar, J. Chem. Google Scholar). and T. E. P. J. 1998; PubMed Scopus Google demonstrated that intraendosomal are in the of for a model the topology of lysosomal digestion, the of the degradation of membrane-bound ceramide by AC in the presence of lysosomal lipids and SAPs. a liposomal assay for AC with the of ceramide degradation as To the acidic of lysosomes as as not only lysosomal such as and dolichol but also a number of lipid degradation such as fatty and dolichol were incorporated into liposomes. In to into how SAPs and AC with and to with surface plasmon resonance spectroscopy binding studies using lipid bilayers of phosphatidylinositol dolichol and dolichol phosphate were from were from acid was from acid was as P. R. B. Scopus Google Scholar). were from or to T. A. J. Biol. Chem. 1990; Full Text PDF PubMed Google Scholar). All other were of the acid ceramidase was purified from to as T. S. Sandhoff K. PubMed Scopus Google Scholar). were from the and and in in the was to a proteins were by and in AC was purified by using and SAP-A, -B, -C, and -D were purified to by using and from to (9Klein A. Henseler M. Klein C. Suzuki K. Harzer K. Sandhoff K. Biochem. Biophys. Res. Commun. 1994; 200: 1440-1448Crossref PubMed Scopus (127) Google Scholar). The and of the SAPs was by and unilamellar were as K. Biochim. Biophys. Acta. PubMed Scopus Google Scholar). of cholesterol ceramide, and other lipids were in and a of and a for at The lipid mixture was to a of in a pH The lipid was in The lipid was through or as indicated in the to the in a were by of with a at for of of and of were composed of and of or and the of lipids was the amount of was the of other components were The assay mixture for the of AC activity the in a final of of pH of AC or as indicated and of were for at and of the sphingosine was as (3Bernardo K. Hurwitz R. Zenk T. Desnick R. J. Ferlinz K. Schuchmann E. H. Sandhoff K. J. Biol. Chem. 1995; 270: 11098-11102Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar). and SAP fibroblasts were for with of in medium The medium was and for a medium both and purified SAPs cells were with with and by Cell were in and total lipids were with 7 of by at were by hydrolysis with of for at were with were for by lipids were to and with by GSLs and were by were with the system. plasmon resonance was at using interaction in a bilayers were on the surface of a of were in to a final of pH and into the the surface was as indicated by a at AC and SAP-D were in pH at a of All are the of at were in All were in the of to of the studies have shown that the activity of various lysosomal including GSL hydrolases and is stimulated by phospholipids such as phosphatidic acid, phosphatidylserine, and (10Zschoche A. Fürst W. Schwarzmann G. Sandhoff K. Eur. J. Biochem. 1994; 222: 83-90Crossref PubMed Scopus (37) Google Scholar, 11Vaccaro A. M. Tatti M. Salvioli R. Ciaffoni F. Gallozzi E. Biochim. Biophys. Acta. 1990; 1033: 73-79Crossref PubMed Scopus (12) Google Scholar, 12Wilkening G. Linke T. Sandhoff K. J. Biol. Chem. 1998; 273: 30271-30278Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar, 13Linke, T. , Wilkening, G. , Lansmann, S. , Moczall, H. , Bartelsen, O. , Weisgerber, J. , and Sandhoff, K. (2000) Biol. Chem. , in Scholar). these lipids and were found to be in the endosomes of cells and in the lysosomal of and in fibroblasts S. J. Biol. Chem. Full Text PDF PubMed Google Scholar, W. Chem. PubMed Scopus Google Scholar, J. Chem. Google Scholar, E. of from of Scholar). a of of the activity of incorporated and into large unilamellar vesicles that of incorporated into the of ceramide was also to the of ceramide was not as as at of The hydrolysis of ceramide in vivo requires the presence of SAP-D and SAP-C (9Klein A. Henseler M. Klein C. Suzuki K. Harzer K. Sandhoff K. Biochem. Biophys. Res. Commun. 1994; 200: 1440-1448Crossref PubMed Scopus (127) Google Scholar). To this in of SAP-D and SAP-C to liposomal assay also to the activity of SAP-D and SAP-C on the of A and that SAP-D required the presence of at or significantly stimulated ceramide In SAP-C was to ceramide degradation to a degree in the absence of However, as both SAP-D and SAP-C were when of these the of SAP-D increased ceramide degradation in both and the the of SAP-C in a for and a of assays that a of and SAP-D or SAP-C the in ceramide degradation The of and SAP-D increased the ceramide degradation and the of and SAP-C stimulated ceramide hydrolysis when with assay mixture of activator proteins and is of the lipids in the cell and of and its phosphate dolichol phosphate were as lipid components of lysosomal T. G. Biochem. J. PubMed Scopus Google Scholar). dolichol was not to ceramide degradation in the presence of SAP-D or SAP-C dolichol phosphate was to ceramide degradation at these only and not SAP-D, in the of ceramide hydrolysis A number of other including and fatty were also for to the degradation of membrane-bound ceramide by The and were incorporated into at a of effect on the of ceramide fatty including and acid the degradation of membrane-bound ceramide to a degree at a of not According to topology GSLs are degraded as membrane-bound components of intralysosomal vesicles and vesicles were observed in fibroblasts of suffering from a prosaposin deficiency. According to studies, the of these vesicles was to be in the of F. B. W. Harzer K. PubMed Scopus Google Scholar). was that this high degree of have on ceramide degradation To this and anionic with The effect of on ceramide hydrolysis was in composed of and The of ceramide hydrolysis was in the absence of SAP-D and in the presence of SAP-D in small unilamellar vesicles as with large unilamellar vesicles In ceramide degradation rates were by the presence of anionic degradation rates were only in in To ceramide was solubilized from the lipid by AC or SAPs during a of experiments. these to ceramide degradation takes as a membrane-bound in the or in both The were to with assay the amount of AC and SAPs were A that the of ceramide hydrolysis in by both in the absence and presence of SAP-C and In degradation rates were not significantly when were as substrate-bearing The of ceramide hydrolysis in the presence of SAP-D or was reduced results that interactions a of binding and SAP-D to the liposomal surface and that ceramide is not solubilized into the by SAP-C and degradation rates of membrane-bound GSLs were observed when the ceramide short (10Zschoche A. Fürst W. Schwarzmann G. Sandhoff K. Eur. J. Biochem. 1994; 222: 83-90Crossref PubMed Scopus (37) Google Scholar, 12Wilkening G. Linke T. Sandhoff K. J. Biol. Chem. 1998; 273: 30271-30278Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar). how the chain of ceramide the of hydrolysis by A that the degradation rates with chain The degradation of was with The degree of by SAP-D and SAP-C was also for the hydrolysis of increased degradation rates were observed with as substrate with both in the absence and presence of SAPs also ceramide with were degraded by AC in liposomal assay system. that the ceramide were hydrolyzed with the SAP-D stimulated the degradation of these ceramide SAP-C the of hydrolysis that ceramide degradation was not only stimulated by SAP-D but also by and were to the degradation of membrane-bound A that SAP-A, -C, and -D but not stimulated the degradation of ceramide in the liposomal assay system. To the a cell culture study in which the SAPs were to the culture medium of fibroblasts of a patient suffering from prosaposin deficiency (5Fürst W. Sandhoff K. Biochim. Biophys. Acta. 1992; 1126: 1-16Crossref PubMed Scopus (246) Google Scholar). The and endocytosis of SAP-A, -B, -C, and -D in a reduction of ceramide storage after of SAP-A, -C, -D but not (9Klein A. Henseler M. Klein C. Suzuki K. Harzer K. Sandhoff K. Biochem. Biophys. Res. Commun. 1994; 200: 1440-1448Crossref PubMed Scopus (127) Google Scholar, S. Klein A. W. A. G. Sandhoff K. Eur. J. Cell Biol. Google 7 SAP-D and reduced ceramide storage by and SAP-C by cell culture results were in with the from in liposomal assay system. The studies that binding of AC and SAP-D to lipid is required for efficient ceramide surface plasmon resonance spectroscopy to the interaction of AC and SAP-D to lipid in The that the binding of SAP-D to bilayers was to that AC also bound significantly to anionic, to lipid The of ceramide effect on the binding of SAP-D or AC not in SAP-D the binding of AC to lipid this SAP-D was into a cell and bound to the lipid by of AC into the However, increased binding of AC was observed when with identical in the absence of SAP-D not The of binding of both SAP-D and AC not only on the presence of anionic lipids in the membrane but also on the pH that the interaction of protein when the pH of the pH the binding of SAP-D to the membrane was at pH The in membrane interaction as a of the pH was for pH the binding of AC to was at pH 4. 0. According to model for the topology of lysosomal digestion, GSLs and are degraded in the acidic compartments of the cell as components of intraendosomal and intralysosomal vesicles and (2Sandhoff K. Kolter T. Trends Cell Biol. 1996; 6: 98-103Abstract Full Text PDF PubMed Scopus (147) Google Scholar). The of ceramide is by lysosomal A study has shown that SAP-D is for the lysosomal degradation of ceramide in vivo (9Klein A. Henseler M. Klein C. Suzuki K. Harzer K. Sandhoff K. Biochem. Biophys. Res. Commun. 1994; 200: 1440-1448Crossref PubMed Scopus (127) Google Scholar). are hydrophobic and primarily as membrane of The of ceramide for AC activity in requires a mixture of synthetic nonionic and anionic detergents (3Bernardo K. Hurwitz R. Zenk T. Desnick R. J. Ferlinz K. Schuchmann E. H. Sandhoff K. J. Biol. Chem. 1995; 270: 11098-11102Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar). However, detergents not in vivo and form in To the intraendosomal and intralysosomal as as a assay at pH was incorporated into different lysosomal The of the was to study ceramide hydrolysis by AC as of the degradation of phospholipids by that the of is on the and of the membrane interface A. M. Annu. Rev. Biochem. 1995; PubMed Scopus Google Scholar). not only the components and lipid but also the of liposomes. is demonstrated in that lysosomal anionic lipids and the hydrolysis of lipids are the assay G. Inc. , New Scholar, G. Linke T. G. Sandhoff K. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The of AC was to be and AC is to be in a lysosomal This that the of AC to the membrane is primarily by interactions and is not A binding was also observed for other lysosomal proteins such as glucocerebrosidase and A. M. Tatti M. Salvioli R. Ciaffoni F. Gallozzi E. Biochim. Biophys. Acta. 1990; 1033: 73-79Crossref PubMed Scopus (12) Google Scholar, 12Wilkening G. Linke T. Sandhoff K. J. Biol. Chem. 1998; 273: 30271-30278Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar, 13Linke, T. , Wilkening, G. , Lansmann, S. , Moczall, H. , Bartelsen, O. , Weisgerber, J. , and Sandhoff, K. (2000) Biol. Chem. , in Scholar). Cell culture studies that SAP-D and also SAP-C increased the activity of AC its membrane-bound substrate ceramide is shown in that SAP-D and were to the degradation of membrane-bound ceramide in vitro, and that SAP-D and required a of or in the lipid a of ceramide hydrolysis The of SAPs on lipids at as the mechanism of A has also been observed for other including protein and D. Biochim. Biophys. Acta. PubMed Scopus Google Scholar). In to SAP-D and SAP-C are only the assay pH 4. 0. also for the that ceramide was stimulated by at different namely SAP-D and a of of anionic in substrate-bearing SAP-D was the of AC SAP-C was to ceramide degradation to a activator proteins to be of other a of lysosomal This effect of SAP-C also to a disease caused by SAP-D deficiency in to and not been observed yet D. Henseler M. S. A. Sandhoff K. J. Inherited PubMed Scopus Google Scholar, A. Linke Biol. Chem. PubMed Scopus Google Scholar, D. M. Sandhoff K. PubMed Scopus Google Scholar). The of interactions also when dolichol or dolichol phosphate was incorporated into substrate-bearing liposomes. lipids were found to membrane and to the of T. G. Biochem. J. PubMed Scopus Google Scholar). lipids hydrophobic interactions and membrane by AC and SAPs. the dolichol was to the of ceramide hydrolysis dolichol not significantly this activity The of ceramide degradation by dolichol phosphate was in to or The that such as the and effect on ceramide degradation that the surface be to the membrane interface to a in ceramide demonstrated that AC high in the absence of detergents H. W. Biochim. Biophys. Acta. PubMed Scopus Google Scholar). This to the that some amino be on the surface of AC and that hydrophobic interactions also a in ceramide This is by the that ceramide degradation in the presence of also place in the absence of anionic phospholipids. To the of interactions with increased membrane curvature. has been shown that the of the of lipids from the to the due to in the surface head group and in the number of in the lipid G. Inc. , New Scholar, D. Biochim. Biophys. Acta. 1996; PubMed Scopus Google Scholar). can be from that increased membrane in to ceramide degradation rates both in the absence and presence of This that both AC and SAP-D into the membrane interface during the of catalysis. the that both and interactions membrane binding of AC and SAP-D and AC bound to at acidic pH to bilayers composed of lipids This also the binding of proteins pH that the in binding not be with the degree of of AC activity observed in the presence of lipids not only membrane binding but also a change in AC in the lipid which the of catalysis. A change in the of a protein after binding to has been for glucocerebrosidase 1998; PubMed Scopus Google Scholar). The also that only a amount of AC was from the lipid during the for the interaction from with The that AC activity was not significantly by a of the liposomal assay mixture that ceramide degradation occurred primarily as a membrane-bound and that SAPs not ceramide into the a mechanism that has been for the degradation of GM2 by A in the presence of the GM2 activator protein (5Fürst W. Sandhoff K. Biochim. Biophys. Acta. 1992; 1126: 1-16Crossref PubMed Scopus (246) Google Scholar). the and be to AC bound to the surface during ceramide hydrolysis D. Biochim. Biophys. Acta. PubMed Scopus Google Scholar). In to the degradation of in which are by the of ceramide is in the of the lipid and is not for a water-soluble AC into the membrane to reach its substrate or the substrate be of the membrane the of the to be with short hydrophobic can be of chain was this also a for ceramide hydrolysis by ceramide with different and sphingosine into liposomes. A that the of degradation with chain of the of This finding that chain required to reach the of AC the short chain have been only the effect of SAPs on the in activity of AC was investigated. In the H. W. Biochim. Biophys. Acta. PubMed Scopus Google the effect of a SAP-C on AC activity was in a but to effect on AC was shown in the study H. W. Biochem. Biophys. 1994; PubMed Scopus Google that AC was specifically stimulated by SAP-D in a assay using a AC from Our results that not only SAP-D but also SAP-C and were to the degradation of ceramide in in cell culture and This result to in to SAP-C and -B, SAP-D deficiency has not yet been as a clinical the four SAPs are was ceramide accumulation found S. Klein A. W. A. G. Sandhoff K. Eur. J. Cell Biol. Google Scholar). the four only not ceramide the that has a high degree of homology to SAP-A, -C, and has been as a E. J. Biol. Chem. 1994; Full Text PDF PubMed Google Scholar). on the model for the hydrolysis of membrane-bound AC to lipid due to and hydrophobic interactions the for the of AC on the membrane for ceramide membrane is by interactions hydrophobic patches on the surface of AC and membrane AC bound to the liposomal surface during and after of ceramide hydrolysis takes place when the substrate the of AC through on that SAP-A, -C, and in with studies in which the lipid binding of SAPs have been M. Salvioli R. Ciaffoni F. Pucci P. Andolfo A. Amoresanp A. Vaccaro A. M. Eur. J. Biochem. 1999; 263: 486-494Crossref PubMed Scopus (24) Google Scholar, A. M. Ciaffoni F. Tatti M. Salvioli R. D. C. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google ceramide hydrolysis by in the lipid the of AC into the interface of the membrane to reach its hydrophobic This model is also by the result that SAPs are to of in A. M. Ciaffoni F. Tatti M. Salvioli R. D. C. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar). Furthermore, proteins can with interactions can be as as by the of K. K. S. F. J. 1999; Google the membrane activity of M. B. A. T. R. B. A. J. 1995; PubMed Scopus Google or the of surface activity of phospholipids by protein M. R. G. F. J. J. 1992; PubMed Scopus Google Scholar). SAP-A, -C, and -D with and membrane-bound AC has not yet been in The of AC by SAP-D has been P. The of Inc. , Scholar). how SAPs substrate is the only SAP that is not to the degradation of ceramide in vivo and in SAP-A, -C, and -D were to ceramide degradation both in and in cell In glucosylceramide degradation is specifically stimulated by SAP-C in vivo and by SAP-C and in into the mechanism of membrane interaction and substrate of SAPs not only studies, including and but also a of the SAPs. Our study the of how the activity of AC is by the presence of lysosomal anionic phospholipids and SAPs.
Linke et al. (Thu,) studied this question.
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