Biomaterial Database

Lactosylceramide beta-galactosidase in human sphingolipidoses. Evidence for two genetically distinct enzymes. 1975

H Tanaka, and K Suzuki

In view of recent conflicting reports from two laboratories, activities of lactosylceramide beta-galactosidase were reinvestigated in detail in brains and livers of normal individuals and of patients with globoid cell leukodystrophy or GM1-gangliosidosis. Both sets of the apparently totally contradictory results were readily reproduced simply by using the different assay systems of the respective laboratories. With our own assay system, hepatic lactosylceramide beta-galactosidase appeared deficient only in Gm1-gangliosidosis, while it appeared deficient only in globoid cell leukodystrophy when the assay system of Wenger et al. (Wenger, D.A., Sattler, M., Clark, D., and McKelvey, H. (1974) Clin. Chim. Acta 56, 199-206) was used. Analyses of individual constitutents in the two assay systems revealed their complex effects on measured activities of the enzyme. The findings were strongly indicative of the existence of two genetically distinct lactosylceramide-cleaving enzymes. One enzyme (lactosylceramidase I) may be identical with galactosylceramide betal-galactosidase, and the other (lactosylceramidase II) is closely related to nonspecific 4-methylumbelliferyl beta-galactosidase. Normal human brain contains mostly lactosylceramidase I, while normal liver contains predominantly lactosylceramidase II. Lactosylceramidase I is genetically lacking globoid cell leukodystrophy, and lactosylceramidase II in GM1-gangliosidosis. Lactosylceramidase I is activated by either pure or crude taurocholate and by oleic acid and is only slightly activated by chloride ions. Lactosylceramidase II is activated by crude taurocholate but not by pure taurocholate. As activators, oleic acid is less effective and chloride more effective than for lactosylceramidase I. Citrate-phosphate buffer is more favorable to lactosylceramidase I than citrate buffer, while lactosylceramidase II responds in reverse. The standard assay system used by Wenger et al. determines almost exclusively lactosylceramidase I, while our own standard system is optimal for lactosylceramidase II and is less favorable for lactosylceramidase I. With a highly purified human hepatic beta-galactosidase preparation, exxentially free of galactosylceramide beta-galactosidase activity, lactosylceramide-cleaving activity determined by the Wenger system was less than 2 per cent of that determined by our system. If lactosylceramide beta-balactosidase assays are to be used for diagnosis of globoid cell leukodystrophy, it is absolutely essential to use an appropriate assay system in order to avoid errors of serious consequences.

UI	MeSH Term	Description	Entries
D007785	Lactose	A disaccharide of GLUCOSE and GALACTOSE in human and cow milk. It is used in pharmacy for tablets, in medicine as a nutrient, and in industry.	Anhydrous Lactose,Lactose, Anhydrous
D007965	Leukodystrophy, Globoid Cell	An autosomal recessive metabolic disorder caused by a deficiency of GALACTOSYLCERAMIDASE leading to intralysosomal accumulation of galactolipids such as GALACTOSYLCERAMIDES and PSYCHOSINE. It is characterized by demyelination associated with large multinucleated globoid cells, predominantly involving the white matter of the central nervous system. The loss of MYELIN disrupts normal conduction of nerve impulses.	Diffuse Globoid Body Sclerosis,Galactosylceramidase Deficiency Disease,Krabbe Disease,Classic Globoid Cell Leukodystrophy,Early-Onset Globoid Cell Leukodystrophy,GALC Deficiency,Galactocerebrosidase Deficiency,Galactosylceramide Lipidosis,Galactosylceramide beta-Galactosidase Deficiency,Galactosylceramide-beta-Galactosidase Deficiency Disease,Galactosylcerebrosidase Deficiency,Galactosylsphingosine Lipidosis,Globoid Body Sclerosis, Diffuse,Globoid Cell Leukodystrophy,Globoid Cell Leukoencephalopathy,Globoid Leukodystrophy,Infantile Globoid Cell Leukodystrophy,Krabbe Leukodystrophy,Krabbe's Disease,Krabbe's Leukodystrophy,Late-Onset Globoid Cell Leukodystrophy,Leukodystrophy, Globoid Cell, Classic,Leukodystrophy, Globoid Cell, Early-Onset,Leukodystrophy, Globoid Cell, Infantile,Leukodystrophy, Globoid Cell, Late-Onset,Psychosine Lipidosis,Cell Leukodystrophies, Globoid,Cell Leukodystrophy, Globoid,Cell Leukoencephalopathies, Globoid,Cell Leukoencephalopathy, Globoid,Deficiencies, GALC,Deficiencies, Galactocerebrosidase,Deficiencies, Galactosylceramide beta-Galactosidase,Deficiency Disease, Galactosylceramidase,Deficiency Disease, Galactosylceramide-beta-Galactosidase,Deficiency Diseases, Galactosylceramidase,Deficiency Diseases, Galactosylceramide-beta-Galactosidase,Deficiency, GALC,Deficiency, Galactocerebrosidase,Deficiency, Galactosylceramide beta-Galactosidase,Disease, Galactosylceramidase Deficiency,Disease, Galactosylceramide-beta-Galactosidase Deficiency,Diseases, Galactosylceramidase Deficiency,Diseases, Galactosylceramide-beta-Galactosidase Deficiency,Early Onset Globoid Cell Leukodystrophy,GALC Deficiencies,Galactocerebrosidase Deficiencies,Galactosylceramidase Deficiency Diseases,Galactosylceramide beta Galactosidase Deficiency,Galactosylceramide beta Galactosidase Deficiency Disease,Galactosylceramide beta-Galactosidase Deficiencies,Galactosylceramide-beta-Galactosidase Deficiency Diseases,Globoid Cell Leukodystrophies,Globoid Cell Leukoencephalopathies,Globoid Leukodystrophies,Krabbes Disease,Krabbes Leukodystrophy,Late Onset Globoid Cell Leukodystrophy,Leukodystrophies, Globoid,Leukodystrophies, Globoid Cell,Leukodystrophy, Globoid,Leukodystrophy, Krabbe,Leukodystrophy, Krabbe's,Leukoencephalopathies, Globoid Cell,Leukoencephalopathy, Globoid Cell,beta-Galactosidase Deficiencies, Galactosylceramide,beta-Galactosidase Deficiency, Galactosylceramide
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008967	Molecular Biology	A discipline concerned with studying biological phenomena in terms of the chemical and physical interactions of molecules.	Biochemical Genetics,Biology, Molecular,Genetics, Biochemical,Genetics, Molecular,Molecular Genetics,Biochemical Genetic,Genetic, Biochemical,Genetic, Molecular,Molecular Genetic
D009829	Oleic Acids	A group of fatty acids that contain 18 carbon atoms and a double bond at the omega 9 carbon.	Octadecenoic Acids,Acids, Octadecenoic,Acids, Oleic
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D002021	Buffers	A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer.	Buffer
D002554	Cerebrosides	Neutral glycosphingolipids that contain a monosaccharide, normally glucose or galactose, in 1-ortho-beta-glycosidic linkage with the primary alcohol of an N-acyl sphingoid (ceramide). In plants the monosaccharide is normally glucose and the sphingoid usually phytosphingosine. In animals, the monosaccharide is usually galactose, though this may vary with the tissue and the sphingoid is usually sphingosine or dihydrosphingosine. (From Oxford Dictionary of Biochemistry and Molecular Biology, 1st ed)
D003374	Coumarins	Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.	1,2-Benzopyrone Derivatives,1,2-Benzopyrones,Coumarin Derivative,Coumarine,1,2-Benzo-Pyrones,Benzopyran-2-ones,Coumarin Derivatives,Coumarines,1,2 Benzo Pyrones,1,2 Benzopyrone Derivatives,1,2 Benzopyrones,Benzopyran 2 ones,Derivative, Coumarin,Derivatives, 1,2-Benzopyrone,Derivatives, Coumarin
D005690	Galactose	An aldohexose that occurs naturally in the D-form in lactose, cerebrosides, gangliosides, and mucoproteins. Deficiency of galactosyl-1-phosphate uridyltransferase (GALACTOSE-1-PHOSPHATE URIDYL-TRANSFERASE DEFICIENCY DISEASE) causes an error in galactose metabolism called GALACTOSEMIA, resulting in elevations of galactose in the blood.	D-Galactose,Galactopyranose,Galactopyranoside,D Galactose