Biosynthesis of Triacylglycerol, Phospholipid, Sphingolipid

1. Metabolism I
Unit 4:
Biosynthesis of
Triacylglycerol, Phospholipids,
Sphingolipids
Semester: II
Dr. Nibedita Pradhan
Department of Life Science
Kristu Jayanti College
May 2023

2. Triacylglycerol Biosynthesis
Acylation
Reduction
Reduction
Acylation
Adipose tissue
Liver/Kidney

3. Acylation
dephosphorylation
Acylation

4. Phospholipids include:
(i) glycerophospholipids: the alcohol is glycerol
(ii) sphingophospholipids : the alcohol is sphingosine
Glycerophospholipids is derived from 1,2-diacylglycerol-
3-phosphate (or phosphatidic acid)
Glycerol
Sphingosine
OH
H2C
CH
HO
H2C OH
H
O
H
2
N
O
H
O
H
2
C
C
H
O
H
2
C
O
C
O
R
1
C
O
R
2
P
1,2-diacylglycerol-3-phosphate

5. ➢ The important glycerophospholipids are:
Phosphatidyl choline (lecithin)
Phosphatidyl ethanolamine (cephalin)
Phosphatidyl inositol
Phosphatidyl serine
Diphosphatidyl glycerol (cardiolipin)
Plasmalogen
➢ The only phosphosphingolipid is sphingomyelin
➢ Sphingomyelin is found predominantly in myelin sheath

6. ➢ Many different phospholipid species can be Constructed by
combining various fatty acids and polar Head groups with the
glycerol or sphingosine backbone
➢ All the biosynthetic pathways follow a few basic patterns.
➢ In general, the assembly of Phospholipids from simple precursors
requires
1. synthesis of the backbone molecule (glycerol or sphingosine);
2. attachment of fatty acid(s) to the backbone through an ester
or amide linkage;
3. addition of a hydrophilic head group to the backbone through
a phosphodiester linkage; and, in some cases,
4. Alteration or exchange of the headgroup to yield the final
phospholipid product.
➢ In eukaryotic cells, phospholipid synthesis occurs primarily on
the surfaces of the smooth endoplasmic reticulum and the
mitochondrial inner membrane.
➢ Some newly formed phospholipids remain at the site of
synthesis, but most are destined for other cellular locations.

9. Synthesis of lecithin
Lecithin is synthesized from activated choline and diacylglycerol
Activated form of choline is CDP-choline
A phosphate group is transferred from ATP to choline forming phosphocholine
A cytidyl group is transferred from CTP to phosphocholine forming CDP-choline
Phosphocholine is transferred from CDP-choline to diacylglycerol forming lecithin

10. Synthesis of Cephalin
Synthetic pathway for cephalin is similar to that for lecithin
Ethanolamine is activated to CDP ethanolamine
This reacts with diacylglycerol to form cephalin

11. Synthesis of phosphatidyl serine
Phosphatidyl serine is synthesized from CDP-diacylglycerol and serine
CDP-Diacylglycerol is formed from phosphatidic acid
CDP-Diacylglycerol reacts with serine to form phosphatidyl serine

12. Synthesis of phosphatidyl inositol
Phosphatidyl inositol is synthesized from CDP-diacylglycerol and inositol
CDP-Diacylglycerol is formed from phosphatidic acid
CDP-Diacylglycerol reacts with inositol to form phosphatidyl inositol

14. Conversion of PS to PE
Glycerophospholipids can undergo interconversion
Serine residue of phosphatidyl serine can be decarboxylated to
ethanolamine
This converts phosphatidyl serine into phosphatidyl ethanolamine

15. Conversion of PE to PC
Ethanolamine residue of phosphatidyl ethanolamine can be methylated
Addition of three methyl groups converts ethanolamine into choline
Thus, phosphatidyl choline can be formed from phosphatidyl
ethanolamine

16. Synthesis of cardiolipin
Cardiolipin is diphosphatidyl glycerol
It is found only in mitochondria where it is synthesized from:
Two molecules of CDP-diacylglycerol, One molecule of glycerol-3-
phosphate
A phosphatidate group is transferred from CDP-diacylglycerol to
glycerol-3-phosphate; The product is phosphatidyl glycerol-3-
phosphate
The phosphate group is split off to form phosphatidyl glycerol
Phosphatidyl glycerol reacts with another molecule of CDP-
diacylglycerol
A phosphatidate group is transferred from CDP-diacylglycerol to
phosphatidyl glycerol
The product is diphosphatidyl glycerol

18. Synthesis of plasmalogens
Plasmalogens are synthesized from:
1. Dihydroxyacetone phosphate
2. Acyl CoA
3. A long-chain alcohol
4. CDP-Ethanolamine
➢ At first, a fatty acyl group is added to C1 of
dihydroxyacetone phosphate (DHAP). Then, the acyl group
is replaced by an alkyl group. 1-Alkyl DHAP is then reduced
to 1-alkyl glycerol-3-phosphate
➢ An acyl group is added to C2 of 1-alkyl glycerol-3-phosphate
➢ The phosphate is removed from C3
➢ Phosphoethanolamine is added to C3

22. ➢ In some plasmalogens, ethanolamine is replaced by choline or serine
➢ Ethanolamine plasmalogen is present in myelin
➢ Choline plasmalogen is abundant in cardiac tissue
➢ Serine plasmalogen is present in retina and white matter
➢ Platelet activating factor (PAF) is a specific type of plasmalogen
➢ It has an alkyl group (generally 16-carbon) at position 1
➢ The acyl group at position 2 is acetate
➢ Phosphocholine is present at position 3

23. Sphingomyelin is synthesized from ceramide and phosphatidyl
choline
Ceramide is acyl sphingosine

24. Condensation
Reduction
Acylation

25. Oxidation
Addition of head group