Download LECT 23 Cmplxlipsyn

Triacylglycerol Synthesis
• Fatty acyl-CoA
• DHAP reduction to glycerol-PO4
or
• Glycerol kinase to glycerol-PO4
O
• Two esterifications
R-C-O
• Diacylglycerol-PO4 intermediate
• Triacylglycerol
O
O-C-R
O
O-C-R
Triacylglycerol Biosynthesis
glycolysis
CH2OH
C=O
CH2OP
DHAP
NADH + NAD+
CH2OH ADP ATP
CH2OH
HO-C-H
HO-C-H
glycerol kinase
CH
OP
CH2OH
2
glycerol-PO4
dehydrogenase
Glycerol-PO4
O
Not in adipose
tissue
O
CH2O-C-R
2 R-C~CoA
Phosphatidic
acid
O
R-C-O-C-H
CH2OP
H2O
PO4
O
R-C~CoA
O
CH2O-C-R
O
Phospholipid
R-C-O-C-H
biosynthesis
1,2 Diacylglycerol CH2OH
(DAG)
O
O CH2O-C-R
R-C-O-C-H O
CH2O-C-R
Question
• Can a triacylglycerol (triglyceride) storage
fat be synthesized entirely from glucose,
i.e., every carbon in the fat comes from a
sugar?
• Answer:
YES
Phospholipid
Biosynthesis
(smooth ER)
O
O CH2O-C-R
R-C-O-C-H
O
CH2OPO
O
Ester linkage
- or +
Phosphatidic
Acid
- or +
Polar component
= choline, serine, ethanolamine, etc
Glycerophospholipids
O
O CH2O-C-R
R-C-O-C-H O
+
CH2OPO-CH2CH2-N(CH3)3
O
Phosphatidylcholine or lecithin
Strategy of Glycerophospholipid
Biosynthesis
• Activate diacylglycerol
• Activate appending moiety (salvage)
NH2
N
O
N
PPP- Ribose
CTP
Bacteria (Prokaryotes)
Activate Phosphatidic acid
Phosphatidic acid + CTP
CDP-diacylglycerol
+ PPi
O
O CH2O-C-R
R-C-O-C-H
CH2OP~P-ribose-Cytosine
(CDP-diacylglycerol)
Bacteria (Prokaryotes)
CDP-diacylglycerol
Serine
CMP
Phosphatidylserine
CO2
Phosphatidylethanolamine
Glycerol-PO4
CMP
Phosphatidylglycerol-3-PO4
glycerol
Phosphatidylglycerol
Cardiolipin
Wassermann antigen for diagnosing
Most prominent membrane lipid in bacteria syphilis
Eukaryotes
DHAP
1
Glycerol-3-PO4
2
ATP
Glycerol
FA-CoA
1-Acyl-DHAP
NADPH
1-Acyl-glycerol-3-PO4
O
O CH2O-C-R Phosphatidic acid
3
R-C-O-C-H
DAG
CH2OP
ATP
CTP
O
O CH2O-C-R
R-C-O-C-H
CH2OH
1,2 DAG
Pi
CDP-diacylglycerol
ethanolamine (CDP-ethanolamine)
choline (CDP-choline)
Serine (phosphatidylethanolamine)
Glycerol (CDP-diacylglycerol)
Inositol (CDP-diacylglycerol)
Cardiolipin (phosphatidylglycerol)
NH2
N
O
O
O
N
+
(CH3) N CH2CH2 O P O P O CH2
3
O
O
O
Cytidine diphosphate (CDP) choline HO
OH
NH2
N
O
+
O
H N CH2CH2 O P O P
3
O
O
Cytidine diphosphate (CDP)ethanolamine
O
N
O CH2
O
HO
OH
Ethanolamine or
choline
HO-CH2-CH2-NH3+
ATP
ADP
O
SALVAGE
Ethanolamine kinase or
choline kinase
HO-P-O-CH2-CH2-NH3+
O-
CTP
Phosphoethanolamine
PPi
O
O
Cytidine--P- O-P- O-CH2-CH2-NH3+
O-
O-
DAG
CDP-ethanolamine
CMP
Phosphatidylethanolamine
Serine
Phosphatidylserine
Ethanolamine