1. Biochemistry NEUROPSYCHIATRY BLOCK
NERV222 Lecture 1 Biochemistry of Myelin
Biochemistry Department /2019
Nervous system Block NERV 222
September 2018

2. Outlines Objectives. Background. Key principles. Take home messages.
September 2018

3. Objectives By the end of this lecture, the students should be able to:
Recognize the sphingolipids class of lipid, their chemical structure, tissue distribution and functions.
Be familiar with the biochemical structure, and function of myelin.
Describe the basics of biosynthesis and degradation of sphingolipids.
- Discuss sphingolipidosis group of diseases.
September 2018

4. Sphingolipids: Background
Essential component of membranes.
Abundant in nervous tissue.
Also exist extra-nervous tissue:
e.g. Cell surface receptors for cholera, diphtheria and tetanus toxins as well as for certain viruses.
September 2018

5. Sphingolipids: Background
Regulation of growth and development.
Very antigenic: the carbohydrate portion of a glycolipid is the antigenic determinant
Blood group antigen
Embryonic antigen
Tumor antigen
Cell transformation.
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6. Key Principles Chemical structure of Sphingolipids. Types:
Glycosphingolipids (Glycolipids).
Sphingophospholipids, e.g. Sphingomyelin.
Myelin structure and function.
Sphingolipidosis.
September 2018

7. Sphingolipids: Structure and types
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8. Sphingosine CH3 (CH2)12 CH CH CH CH CH2OH OH NH2
Long chain, unsaturated amino alcohol OH
NH2
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9. Ceramide = Sphingosine + Fatty acid
Long chain fatty acid
CH3 (CH2)12 CH CH CH CH CH2OH OH NH C O
(CH2)n
CH3
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10. Sphingomyelin = Ceramide + Phosphorylcholine
Long chain fatty acid
CH3 (CH2)12 CH CH CH CH CH2O OH NH C O
(CH2)n
CH3
Phosphorylcholine
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11. Cerebrosides = Ceramide + Monosaccharides
e.g. Galactocerebroside.
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12. Gangliosides Gangliosides = Ceramide oligosaccharides + NANA e.g. GM2.
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13. Sphingolipids’ Synthesis
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14. Myelin Structure
Myelin is a specialized cell membrane that ensheathes an axon to form a myelinated nerve fiber.
Myelin is produced by:
Schwann cells: Periphral nerves.
Oligodendrocytes: CNS.
Myelin composition:
Lipids (80%): Main component: Cerebrosides
Other component: Sphingomyelin
Proteins (20%): e.g. Myelin basic protein
September 2018

15. Very long chain fatty acids
Myelin Structure
Fatty acid of Sphingomyelin:
Myelin sheath:
Very long chain fatty acids
Lignoceric 24:0
Nervonic :1
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16. Myelin Structure and function
Myelin sheath insulates the nerve axon to avoid signal leakage and greatly speeds up the transmission of impulses along axons.
Multiple sclerosis:
Neuro-degenerative, auto-immune disease.
Breakdown of myelin sheath (demyelination).
Defective transmission of nerve impulses.
Direction of nerve impulse
September 2018

17. Degradation
Sphingolipids are degraded by lysosomal hydrolytic enzymes.
If a specific lysosomal hydrolase is partially or totally
missing, a sphingolipid accumulates in the lysosomes,
producing lipid storage diseases or sphingolipidosis.
September 2018

18. Sphingolipidosis Synthesis (Normal); Degradation (Defective).
Substrate accumulates in organs..
Progressive, early death.
Phenotypic and genotypic variability.
Autosomal recessive (mostly).
Rare, Except in Ashkenazi Jewish.
September 2018

19. Sphingolipidosis Diagnosis: Measure enzyme activity:
Cultured fibroblasts or peripheral leukocytes.
Cultured amniocytes (prenatal).
Histologic examination.
DNA analysis.
Treatment:
Replacement Therapy: e.g. Recombinant human enzyme.
Bone marrow transplantation: e.g. Gaucher disease.
September 2018

20. Sphingolipidosis
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21. Niemann-pick disease
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22. Gaucher disease
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23. Take home messages
Sphingolipids are complex lipids that includes sphingo-phospholipids and glycolipids.
Ceramide is the precursor of all sphingolipids.
Sphingolipids are present mainly in nerve tissue, but they are also found extra- neural.
Myelin sheath insulates the nerve axon to avoid signal leakage and speed up impulse transmission.
Sphingolipidosis are rare genetic diseases due to defective degeneration of sphingolipids.
September 2018

24. Reference
Lippincott Illustrated Review of Biochemistry, 6th edition, 2014, Unit 3, Chapter 17, Pages
. KSUMC Lecture note.
September 2018

25. THANKS
September 2018