Metabolism of sphingolipids

Metabolism of sphingomyelin, cerebrosides, sulphatides and gangliosides

1. Metabolism of Sphingolipids R. C. Gupta Professor and Head Department of Biochemistry National Institute of Medical Sciences Jaipur, India

2. The sphingolipids are of two types : Phospho-sphingolipids Glyco- sphingolipids The only phospho sphingolipid is sphingomyelin Glycosphingolipids include the cerebro-sides, sulphatides and gangliosides

3. Synthesis of sphingolipids

4. Synthesis of sphingomyelin

5. Sphingomyelins are synthesized from: Ceramide Phosphatidyl choline S ynthesis of sphingomyelins occurs: In Golgi apparatus On cell membrane

6. Catabolism of sphingomyelins

7. Synthesis of glycosphingolipids

8. The fatty acids in galactocerebrosides are: Cerebronic acid in cerebron Nervonic acid in nervon Oxynervonic acid in oxynervon Lignoceric acid in kerasin

9. Synthesis of sulphatides

10. Galactosylceramide sulphotransferase G alactocerebroside S ulphatide Phosphoadenosine phosphosulphate Phosphoadenosine phosphate  

11. Synthesis of gangliosides Gangliosides are synthesized from: Ceramide Activated hexoses Activated hexosamines N-Acetyl neuraminic acid (NANA)

12. In the name of the gangliosides: The letter G means ganglioside This is followed by subscript letter M, D, T or Q This indicates the number of NANA residues (mono, di, tri or quatra) The subscript numbers 1, 2 and 3 indicate the carbohydrate sequence

13. Catabolism of glycosphingolipids

14. Sphingolipidoses are i nborn errors of sphingolipid metabolism Some catabolic enzyme is d eficient Sphingolipids accumulate in the body due to decreased breakdown Sphingolipidoses

15. Generalized gangliosidosis Deficiency of G M1 - b -galactosidase Breakdown of G M1 ganglioside is impaired G M1 ganglioside accumulates in the tissues Causes mental retardation, hepatomegaly and skeletal deformities

16. Tay-Sachs disease Deficiency of hexosaminidase A Accumulation of G M2 ganglioside Causes mental retardation, blindness, hypotonia and paralysis Fatal by 3-4 years of age

17. Gaucher's disease Deficiency of b -glucosidase Accumulation of glucosyl ceramide ( glucocerebroside) Causes mental retardation, hepatosplenomegaly, hypersplenism and erosion of bones

18. Krabbe's disease Deficiency of b -galactosidase Accumulation of galactosyl ceramide (galactocerebroside) Causes mental retardation, blindness, deafness, hypertonia and hyperirritability

19. Metachromatic leukodystrophy Deficiency of arylsulphatase A Accumulation of sulphatides Causes dementia and progressive paralysis Fatal by 3-10 years of age

20. Niemann-Pick disease Deficiency of sphingomyelinase Accumulation of sphingomyelin Causes mental retardation, motor disturbances, growth failure and hepatosplenomegaly Fatal by four years of age

21. Antenatal diagnosis of sphingolipidoses is possible Abnormal sphingolipids can be detected in foetal cells present in amniotic fluid

22. Inheritance of sphingolipidoses is autosomal recessive The disease occurs only in homozygotes Heterozygotes can transmit the defect to their offsprings

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