Lysosomal Storage Disorders

Lysosomal storage diseases are a group of metabolic disorders caused by the lack of key enzymes important for lysosomes to perform their normal function. While clinical trials are underway, there are few approved treatments for lysosomal storage diseases. Current research is focused on finding reliable biomarkers that can be used in these screening programs. Cayman scientists have developed LC-MS/MS assay workflows for quantitative measurement of the activity of certain key enzymes. We also offer a wide range of glycosphingolipid standards associated with the ten main sphingolipidoses that affect the glycosphingolipid pathway.

Determination of Lysosomal Acid Lipase Deficiency Lysosomal Acid Lipase Activity MaxSpec® Assay Kit – Item No. 24854 ·· Easy-to-use reagent kit for the quantification of lysosomal acid lipase activity in dried blood spots ·· Designed for use in LC-MS-based or fluorometry applications ·· Includes necessary substrate, product, and internal standard, each provided at known concentrations

O O O O LC-MS/MS

LAL Activity MaxSpec® Assay Substrate

HO O O HO O O 13C Detect LAL

13CH Product and 13C calculate enzyme 13 H2 C activity LAL Activity ® LAL Activity MaxSpec Assay Internal Standard MaxSpec® Assay Product 13 (aka C4-PMHC)

Fluorometry

Dried Blood Spot

Lysosomal Acid Lipase Activity MaxSpec® Assay Kit Workflow Related Products Item No. Product Name Description

16089 4-Methylumbelliferyl Palmitate Fluorogenic substrate for LAL

23891 Lalistat 1 An inhibitor of LAL (IC50 = 68 nM)

25347 Lalistat 2 An inhibitor of LAL (IC50 = 152 nM)

601810 Lysosomal Staining Kit (Red Fluorescence) For imaging of lysosomes in live cells

25152 LysoBrite™ Blue A lysosomal dye

25154 LysoBrite™ Green A lysosomal dye

25157 LysoBrite™ Red A lysosomal dye

Learn more at www.caymanchem.com/lysosomalstorage

2019 CAYMAN CHEMICAL · 1180 EAST ELLSWORTH ROAD · ANN ARBOR, MI 48108 · USA · (800) 364-9897 WWW.CAYMANCHEM.COM Sphingolipid Biomarkers Sphingolipidoses (sphingolipid lysosomal storage disorders) result in an accumulation of various sphingolipids in the lysosome. Ten main sphingolipidoses affect the glycosphingolipid pathway: Farber, Krabbe, Gaucher, Metachromatic

Leukodystrophy, Fabry, Sandhoff, Niemann-Pick, Sialidosis, Tay-Sachs, and GM1 gangliosidosis. All of these disorders are characterized by an accumulation of sphingolipids in the lysosome due to enzyme deficiency or ineffective transport of lipids from the lysosme. The schematics below detail the enzymes associated with these disorders and the sphingolipid products they produce. Sphingosine NH2 HO C13H27 NH NH OH Sphingosine and Ceramide Accumulation 2 Sphingosine 2 Sphingosine HO C13H27 HO C13H27 OH OH Item No. Product Name Acid Ceramidase O Farber’s Disease O O HO R 9000415 C6 Biotin Ceramide (d18:1/6:0) CH Sphingomyelinase 3 O R R + Acid Ceramidase HO HO H3C N Farber’s Disease Niemann-Pick Disease O P OH 22532 C17 Ceramide (d18:1/17:0) CH3 Types A and B OH Sphingomyelin O O 24396 C18 Ceramide-d3 (d18:1/18:0-d3) O O CH R Ceramide 3 O R HN Ceramide R R HN Ceramide HN HN H C N+ 3 HO C13H27 24428 C18 dihydro Ceramide-d (d18:0/18:0-d ) O P O C13H27 3 3 HO C13H27 HO C13H27 CH3 OH OH OH β-Glucosidase OH OH OH 24464 C18 Ceramide-1-Phosphate-d (d18:1/18:0-d ) HO O 3 3 Gaucher Disease OH HO OH OH OH OH O β-Glucosidase HO O 10007907 Sphingosine (d18:1) OH OH β-Galactosidase HO Gauchers Disease HO Krabbe Disease OH OH O 24371 Sphingosine-d9 (d18:1) O OH HN R O OH OH R Glucosylcerebroside HO O C13H27 HN HO O O Glucosylceramide Accumulation OH OH Galactosylcerebroside O C13H27 HO OH R OH Glucosylcerebroside HN OH O HO O C13H27 Item No. Product Name HO β-Galactosidase OHOH OH OH O Krabbe Disease OH 2- 23206 Glucocerebrosides (buttermilk) HO Arylsulfatase A SO4 OH Metochromatic Leukodystrophy OHOH β-Galactosidase O 23207 Glucocerebrosides (Gaucher’s spleen) OH O O Krabbe Disease HO OHOH OH R OH O HN OH OH R 25850 Glucocerebrosides (soy) O HN Lactosylceramide HO O O C H O HO 13 27 OH O C13H27 OH OH Sulfatide HO3SO OH 24621 C16 Glucosylceramide-d3 (d18:1/16:0-d3) OH O OHOH HO OH R O HN 23208 C6 Biotin Glucosylceramide (d18:1/6:0) AcHN Lactosylceramide O HO O Ganglioside Neuraminidase OH HO O O C13H27 HO OH HO Sialadosis HO2C OH OH 23209 C6 NBD Glucosylceramide (d18:1/6:0) OH

O 23213 1-β-D-Glucosylsphingadienine (d18:2 (4E,8E)) OHOH OH R O HN α-Galactosidase A OHOH O O O O 13 O C13H27 Fabry Disease 23212 C Glucosylsphingosine (d18:1) OH HO OH 6 G OH OH HO M3 HO O CO2H OH 23211 1-β-D-Glucosylsphingosine (d18:1) AcHN HO OH OH 24473 N-Glycine Glucosylsphingosine (d18:1) OHOH OHOH Hexosaminidase A O HO OH O Tay-Sachs Disease Gb3 (CTH) NHAc HO O Sandhoff Disease OH OHOH O OH Galactosylceramide Accumulation OH HN R O O O HO O O OH HO O C H OH R O 13 27 Item No. Product Name NHAc O HN HO O OH O O OH OH G O C13H27 M2 OH HO HO OH OH 24471 C6 Galactosylceramide-biotin O CO2H AcHN β-Hexosaminidase A + B 22830 C6 NBD Galactosylceramide (d18:1/6:0) HO OH OHOH OH Sandhoff Disease O HO OH 24466 C15 Galactosylceramide (d18:1/15:0) OHOH NHAc Acid β-Galactosidase O HO OH GM1 Gangliosidosis 22851 C12 NBD Galactosylceramide (d18:1/6:0) OH OH OHOH OH OHOH OHOH O 24467 C18 Galactosylceramide-d (d18:1/18:0-d ) O Gb O 35 35 O O 4 HO O O O OH O HO OH R OH G NHAc O HN NHAc O OH 24322 Galactosylcerebrosides (bovine) M1 OH O OH R O O O C13H27 O HN HO O OH HO O HO O CO H OH OH O C13H27 2 OH HO 20338 Galactosylsphingosine (d18:1) OH OH AcHN HO OH 24620 N-Glycine Galactosylsphingosine (d18:1) OH

Lipid Class Enzyme Deficiency Associated Disorder

2019 CAYMAN CHEMICAL · 1180 EAST ELLSWORTH ROAD · ANN ARBOR, MI 48108 · USA · (800) 364-9897 WWW.CAYMANCHEM.COM Gangliosides Accumulation Sphingosine NH2 HO C13H27 NH NH OH 2 Sphingosine 2 Item No. Product Name Sphingosine HO C13H27 HO C13H27 OH OH 24852 Ganglioside G -d D3 3 Acid Ceramidase O

O O Farber’s Disease R CH27202 C6 Biotin Ganglioside G (d18:1/6:0) HO 3 O D3 R Sphingomyelinase R Acid Ceramidase HO HO H C N+ Niemann-Pick Disease 3 24840O P OH C6 Biotin Ganglioside G (d18:1/6:0) Farber’s Disease CH M1 Types A and B 3 OH Sphingomyelin 24839 C18 Ganglioside G -d (d18:1/18:0-d ) (ammonium salt) O O M1 3 3 O O CH R Ceramide 3 O R HN Ceramide R R HN Ceramide HN HN 24837 H C N+Lyso-Monosialoganglioside GM1 (ammonium salt) 3 HO C13H27 O P O C13H27 HO C13H27 HO C13H27 CH3 OH OH OH β-Glucosidase OH OH OH 24849 C18 Ganglioside GM2-d3 (d18:1/18:0-d3) (ammonium salt) HO O Gaucher Disease OH HO OH OH OH 24850OH C18 Ganglioside GM3-d3 (d18:1/18:0-d3) (ammonium salt) O β-Glucosidase HO O OH OH β-Galactosidase HO Gauchers Disease HO Krabbe Disease OH OH O Lactosylceramides Accumulation O OH HN R O OH OH ItemR No. Product Name Glucosylcerebroside HO O C13H27 HN HO O O OH OH Galactosylcerebroside O C13H27 HO 16983 Lactosylceramides (bovine brain) OH R OH Glucosylcerebroside HN OH O HO O C13H27 27197 Lactosylceramides (bovine buttermilk) HO β-Galactosidase OHOH OH OH O Krabbe Disease OH 2- HO Arylsulfatase A SO248594 C6 Biotin Lactosylceramide (d18:1/6:0) OH Metochromatic Leukodystrophy OHOH β-Galactosidase O 22828 C6 NBD Lactosylceramide (d18:1/6:0) OH O O Krabbe Disease HO OHOH OH R OH O HN OH OH 22829R C12 NBD Lactosylceramide (d18:1/12:0) O HN Lactosylceramide HO O O C H O HO 13 27 OH O C13H27 OH OH Sulfatide HO3SO 24625 C16 Lactosylceramide-d3 (d18:1/16:0-d3) OH OH O OHOH HO OH R 24868 Lactosylsphingosine (d18:1) O HN AcHN Lactosylceramide O HO O Ganglioside Neuraminidase OH HO O O C13H27 HO 24867 Lactosylsphingosine (d18:1) (synthetic) OH HO Sialadosis HO2C OH OH OH

O 24869 N-Glycine Lactosylsphingosine (d18:1) OHOH OH R O HN α-Galactosidase A OHOH O O O O O C13H27 Fabry Disease OH HO Ceramide Trihexosides (Globotriaosylceramides) OH G OH OH HO M3 HO O CO2H Accumulation OH AcHN HO OH OH Item No. Product Name OHOH OHOH Hexosaminidase A O HO OH 24870 Globotriaosylceramides (porcine) O Tay-Sachs Disease Gb3 (CTH) NHAc HO O Sandhoff Disease OH OHOH 24873 Lyso-Globotriaosylceramide (d18:1) O OH OH HN R O O O HO O O OH HO O O C H OH R 24628 C12 NBD Globotriaosylceramide (C18:1/12:0) 13 27 NHAc O HN HO O OH O O OH OH G O C13H27 M2 OH HO OH 24876 C17 Globotriaosylceramide (d18:1/17:0) HO O CO2H OH AcHN 24626 C18 Globotriaosylceramide-d (d18:1/18:0-d ) β-Hexosaminidase A + B HO OH 3 3 OHOH OH Sandhoff Disease O 24874 N-Glycine Globotriaosylsphingosine (d18:1) HO OH OHOH NHAc Acid β-Galactosidase O HO OH GM1 Gangliosidosis OH Globosides (Globotetrahexosylceramides) Accumulation OH OHOH OH OHOH OHOH Item No. Product Name O O Gb O O O 4 HO O O O OH O HO OH R OH G NHAc O HN 24881 Globotetraosylceramides (porcine RBC) NHAc O OH M1 OH O OH R O O O C13H27 O HN HO O OH HO O HO O CO H OH OH O C13H27 2 OH HO OH OH AcHN HO OH OH Lipid Class Enzyme Deficiency Associated Disorder

2019 CAYMAN CHEMICAL · 1180 EAST ELLSWORTH ROAD · ANN ARBOR, MI 48108 · USA · (800) 364-9897 WWW.CAYMANCHEM.COM Sphingosine NH2 HO C13H27 NH NH OH 2 Sphingosine 2 SphingoSphingosylphosphorylcholinesine HOAccumulationC13H27 HO C13H27 OH OH Item No. Product Name Acid Ceramidase O O O Farber’s Disease R CH HO 3 O R Sphingomyelinase R Acid Ceramidase HO HO H C N+ 24328 C6 NBD Sphingomyelin (d18:1/6:0) Niemann-Pick Disease 3 O P OH Farber’s Disease CH Types A and B 3 OH Sphingomyelin 24329 C12 NBD Sphingomyelin (d18:1/12:0) O O O O CH R Ceramide 3 O R HN Ceramide R R HN Ceramide 10007946 C16 Sphingomyelin (d18:1/16:0)HN HN H C N+ 3 HO C13H27 O P O C13H27 HO C13H27 HO C13H27 CH3 OH OH OH β-Glucosidase 13 OH OH OH 24452 C C16HO SphingomyelinO (d18:1/16:0) Gaucher Disease OH HO OH OH OH OH O β-Glucosidase HO O 24354 C17 D-erythro/L-threo Sphingomyelin (d18:1/17:0) OH OH β-Galactosidase HO Gauchers Disease HO Krabbe Disease OH OH O O Sulfatides AccumulationOH HN R O OH OH R Glucosylcerebroside HO O C13H27 HN HO O O OH OH Galactosylcerebroside O C13H27 Item No. Product Name HO OH R OH Glucosylcerebroside HN OH O HO O C13H27 24323 Sulfatides (bovine) (sodium salt) HO β-Galactosidase OHOH OH OH O OH Krabbe Disease Arylsulfatase A SO 2- 24624 C18HO 3'-sulfo Galactosylceramide-d (d18:1/18:0-d ) 4 OH 3 3 Metochromatic Leukodystrophy OHOH β-Galactosidase O OH O O Krabbe Disease HO 24627 OHC12OH NBD 3'-sulfo Galactosylceramide (d18:1/12:0) OH R OH O HN OH OH R O HN Lactosylceramide HO O O C H O HO 13 27 25316 3’-sulfoOH Galactosylsphingosine (ammonium salt) O C13H27 OH OH Sulfatide HO3SO OH OH O OHOH 27200 N-GlycineHO 3’-sulfo Galactosylsphingosine OH R O HN AcHN Lactosylceramide O HO O Ganglioside Neuraminidase OH HO O O C13H27 24858 C6HO Biotin 3'-sulfo Galactosylceramide (d18:1/6:0) Lipid Class Enzyme Deficiency Associated Disorder OH HO Sialadosis HO2C OH OH OH

O OHOH OH R O HN α-Galactosidase A OHOH O O O O O C13H27 Fabry Disease OH HO OH G OH OH HO M3 HO O CO2H View a complete list of our glycosphingolipids at www.caymanchem.com OH AcHN HO OH OH OHOH OHOH Hexosaminidase A O HO OH O Tay-Sachs Disease Gb3 (CTH) NHAc HO O Sandhoff Disease OH OHOH O OH OH HN R O O O HO O O OH HO O C H OH R O 13 27 NHAc O HN HO O OH O O OH OH G O C13H27 M2 OH HO OH HO O CO2H OH

AcHN β-Hexosaminidase A + B HO OH OHOH OH Sandhoff Disease O HO OH OHOH NHAc Acid β-Galactosidase O HO OH GM1 Gangliosidosis OH OH OHOH OH OHOH OHOH O O Gb O O O 4 HO O O O OH O HO OH R OH G NHAc O HN NHAc O OH M1 OH O OH R O O O C13H27 O HN HO O OH HO O HO O CO H OH OH O C13H27 2 OH HO OH OH AcHN HO OH OH

2019 CAYMAN CHEMICAL · 1180 EAST ELLSWORTH ROAD · ANN ARBOR, MI 48108 · USA · (800) 364-9897 WWW.CAYMANCHEM.COM