N-hexyl-O-glucosyl sphingosine, an inhibitor of glucosyl ceramide -glucosidase.

Paper

N-hexyl-O-glucosyl sphingosine, an inhibitor of glucosyl ceramide -glucosidase.

Published Mar 1, 1973 · J. Erickson, N. Radin

Journal of lipid research

Q1 SJR score

61

Citations

1

Influential Citations

Semantic Scholar

Abstract

A synthetic analog of glucocerebroside, N-hexyl-O-glucosyl sphingosine, was found to inhibit the glucosidase in rat spleen that hydrolyzes glucocerebroside. At a concentration of 1 micro m, the analog inhibited the enzyme by 48%. The mode of action appeared to be competitive, probably aided by tight binding of the amine group to a carboxyl group near the enzyme's active site. Increasing or decreasing the chain length of the n-alkyl group attached to the nitrogen atom led to decreased effectiveness. The inhibitory effect was maximal at pH 7.0, but it was still considerable at the enzyme's optimal pH, 5.0. It is suggested that the compound may be useful for inducing an animal model of Gaucher's disease.

In Vitro Study

Study Snapshot

N-hexyl-O-glucosyl sphingosine effectively inhibits glucocerebroside-hydrolyzing enzymes in rat spleen, potentially useful for inducing an animal model of Gaucher's disease.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

Paper

N-hexyl-O-glucosyl sphingosine, an inhibitor of glucosyl ceramide -glucosidase.

References

Gaucher's disease: deficiency of 'acid' -glucosidase and reconstitution of enzyme activity in vitro.

Gaucher's disease is caused by a deficiency in a specific beta-glucosidase enzyme, and two factors, factor P and factor C, can reconstitute enzyme activity in vitro.

The biosynthesis by brain microsomes of cerebrosides containing nonhydroxy fatty acids.

Brain microsomes can rapidly synthesize cerebrosides containing nonhydroxy fatty acids, with ceramide acting as an intermediate in the process.

Enzymatic synthesis of ceramide-glucose and ceramide-lactose by glycosyltransferases from embryonic chicken brain.

Two glycosyltransferases in embryonic chicken brains synthesize ceramide-glucose and ceramide-lactose, revealing a pathway for disialoganglioside synthesis from ceramide.

Identity of β-glucosidase, β-xylosidase and one of the β-galactosidase activities in human liver when assayed with 4-methylumbelliferyl-β-d-glycosides studies in cases of Gaucher's disease

A single enzyme is responsible for all three activities in Peak III in human liver, and its absence in Gaucher's disease patients suggests a single enzyme is responsible for all three activities.

Enzymic hydrolysis of sphingolipids: Hydrolysis of ceramide glucoside by an enzyme from ox brain.

Ceramide glucoside hydrolysis by beta-glucosidase from ox brain is a non-reversible, pH-dependent, and inhibitor-free process.

Demonstration of a deficiency of glucocerebroside-cleaving enzyme in Gaucher's disease.

A marked attenuation of glucocerebroside-cleaving activity is observed in the spleen of patients with Gaucher's disease.

Analytical separation of nonlipid water soluble substances and gangliosides from other lipids by dextran gel column chromatography

Dextran gel column chromatography effectively separates lipids and gangliosides from water-soluble nonlipids, providing accurate infrared spectra for lipid analysis.

Citations

Imino- and azasugar protonation inside human acid β-glucosidase, the enzyme defective in Gaucher disease.

1-deoxynojirimycin and isofagomine derivatives are protonated by human acid -glucosidase, indicating they act as basic amines in the enzyme, potentially benefiting pharmacological chaperone therapy for Gaucher disease.

Identification of a feedback loop involving β-glucosidase 2 and its product sphingosine sheds light on the molecular mechanisms in Gaucher disease

In Gaucher disease, sphingosine inhibits GBA2 activity, preventing further sphingosine accumulation and cytotoxicity, through a negative feedback loop.

Endogenous β-glucocerebrosidase activity in Abca12−/−epidermis elevates ceramide levels after topical lipid application but does not restore barrier function

Loss of ABCA12 function in skin disrupts ceramide production, leading to increased glucosylceramide levels but not significantly reducing trans-epidermal water loss.

A Guided Tour of the Structural Biology of Gaucher Disease: Acid-β-Glucosidase and Saposin C

Recent structural and biochemical information on acid--glucosidase and saposin C proteins has provided new insights into Gaucher disease biology and pathogenesis, offering potential new therapeutic directions.

Novel easily accessible glucosidase inhibitors: 4-hydroxy-5-alkoxy-1,2-cyclohexanedicarboxylic acids.

Novel inhibitors derived from cyclohexane-1,2-dicarboxylic acids effectively inhibit fungal glycosidases, with potential applications in biotechnology, food industry, and pharmacology.