courtsey of Dr.Nyamwange CHS_Moi

1. Sphingolipid Synthesis
By
Dr. C.I. Nyamwange

2. • The biosynthesis of sphingolipids takes place in four
stages:
1. Synthesis of the 18-carbon amine sphinganine from
palmitoyl-coa and serine;
2. Attachment of a fatty acid in amide linkage to yield
N-acylsphinganine;
3. Desaturation of the sphinganine moiety to form n-
acylsphingosine (ceramide); and
4. Attachment of a head group to produce a
sphingolipid such as a cerebroside or sphingomyelin

3. 1

4. Sphingolipids are then made from
ceramide which is synthesized in the
endoplasmic reticulum from the
amino acid serine

5. • Gangliosides are synthesized from ceramide
by the stepwise addition of activated sugars
(eg, UDPGlc and UDPGal) and a sialic
acid, usually N-acetylneuraminic acid

6. Phospholipid biosynthesis
This pathway is located in peroxisomes.

7. • The synthesis pathway of phospholipids starts by reducing
dihydroxyacetone phosphate to glycerol phosphate, with
NADH as the reductant
• Alternatively, existing glycerol molecules may be
phosphorylated by glycerol kinase.
• This is followed by two successive additions of acyl ester.
Fatty acid (typically 16-18 C atoms) is first converted to the
active CoA thioester by acyl CoA synthetase:
• The last product, 1,2-diacylglycerol-3-phosphate, is also
known as phosphatidic acid, and its phospholipid
derivatives are phosphatidyl-X. Phospholipids also tend to
have a saturated fatty acid in position 1 and an unsaturated
fatty acid in position 2.

9. • Phospholipid precursors are activated by
forming a cytidine diphosphate derivative
• CDP-diacylglycerol contains a high energy
bond between the two phosphates, so can act
as a donor of diacylglycerol (bond breaks
between glycerol and phosphate) or as a
donor of the phosphatidyl radical

11. • Microorganisms use the head group hydroxyl
compound to displace CMP and then link up to
the phosphatidyl radical.
• The amino acid serine , which has a hydroxyl
group side chain provides the head group for the
negative phospholipid, phosphatidyl serine .
• Phosphatidyl serine can then be decarboxylated
to produce the important neutral
phospholipid, phosphatidyl ethanolamine.

13. • In animals, phosphatidyl ethanolamine and
phosphatidyl choline are made by a different
strategy, in which ethanolamine and choline are
activated as CDP ethanolamine and CDP choline
• Diacylglycerol then displaces CMP to bond to the
phosphate attached to the headgroup, as shown
for the synthesis of phosphatidyl choline, a
major animal phospholipid.

15. • The strategy used in animals is optimized for what is called
salvage synthesis, in which existing molecules of
ethanolamine, choline and diacylglyerol are reused.
Phosphatidyl ethanolamine + serine
phosphatidyl ethanolamine serine
transferase
phosphatidyl serine + ethanolamine
CO2 phosphatidyl serine decarboxylase
phosphatidyl ethanolamine
Decarboxylation of phosphatidyl serine produces new
molecules of ethanolamine.

16. The “salvage” pathway from
phosphatidylserine to
phosphatidylethanolamine and
phosphatidylcholine
New molecules of choline are made on
the phospholipid structure of
phophatidyl ethanolamine.
The methyl donor is a compound is S-
adenosyl methionine or SAM
for short, leaving behind S-
adenosylhomocysteine, SAHC

19. Pathway for phosphatidylcholine
synthesis from choline in
mammals.