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Concept
Lipids are substances that are
insoluble or immiscible in water, but
soluble in organic solvents.
Fats (Triglyceride or
triacylglycerole
)
To store and
supply
energy
Lipids
Phospholipids
Glycolipids
Lipoids
Cholesterol
Cholesterol ester
To be
important
membrane
components
Contents
Section 1 Fatty acids
Section 2
Metabolism of Triglycerids
Common Name
Comments
14:0
Myristic acid
Saturated
16:0
Palmitic acid
Saturated
18:0
Stearic acid
Saturated
16:1 9
Palmitoleic acid
Unsaturated
18:1 9
Oleic acid
Unsaturated
18:2 9,12
Linoleic acid
EFA
18:3 9,12,15
Linolenic acid
EFA
20:4 5,8,11,14
Arachidonic acid
EFA
Section 2
Metabolism of Triglycerides
Glycerol
O
O
CH2 O C R1
R2 C O C H
3
CH2 O C R3
Esterification
Diet
Fatty acids
Lipogenesis
Carbohydrate
Amino acids
Steroids
-Oxidation
Acetyl-CoA
TAC
2CO2
Cholesterologenesis
Steroidogenesis
Cholesterol
Ketone bodies
2.1 Degradation of TG
2.1.1 Fat catabolism (lipolysis)
2.1.2 -Oxidation of Fatty acids
2.1.3 Other Oxidations of Fatty acids
2.1.4 Ketone Bodies Formation and
Utilization
glycerol metabolism
Place: liver, kidney, intestine
Note
In muscle cells and adipocytes, the
activity of glycerol kinase is low, so
these tissues cannot use glycerol as
fuel.
O
R
+ HSCoA
O
Fatty acid
AMP + PPi
O
Mg2+
R C
acyl-CoA
S CoA
synthetase
acyl-CoA
ATP
Stage 2
Transport of acyl CoA into the
mitochondria
( rate-limiting step)
Carrier: carnitine
Rate-limiting enzyme
carnitine acyltransferase
CH3
OH
+
H3C N CH2 CH CH2 COO
CH3
Carnitine
CH3
+
H3C N CH2
CH3
SCoA
carnitine
acyltransferase
R
C
CH CH2 COO
HSCoA
Step 1. Dehydrogenate
H3C
H
FAD
(CH2)n
SCoA
Fatty acyl-CoA
acyl-CoA dehydrogenase
FADH2
H3C
(CH2)n
C
H
SCoA
trans-2-enoyl-CoA
Step 2. Hydration
H3C
(CH2)n
Trans-2-enoyl-CoA
H
H2O
H3C
(CH2)n
SCoA
enoyl-CoA Hydratase
OH H
3-L-Hydroxyacyl-CoA
SCoA
Step 3. Dehydrogenate
H3C
OH H
H
NAD+
3-L-Hydroxyacyl-CoA
(CH2)n
NADH + H+
hydroxyacyl-CoA
dehydrogenase
O
H3C
(CH2)n
SCoA
O
CH2
SCoA
-Ketoacyl-CoA
(CH2)n
O
CH2
SCoA
-Ketoacyl-CoA
HSCoA
-Ketothiolase
O
H3C
(CH2)n
O
SCoA + CH3
Fatty acyl-CoA
(2C shorter)
SCoA
Acetyl-CoA
Summary
one cycle of the -oxidation:
fatty acyl-CoA + FAD + NAD+ + HS-CoA
fatty acyl-CoA (2 C less) + FADH2 +
NADH + H+ + acetyl-CoA
72
respiratory chain
Acyl-CoA oxidase
-oxidation
3. Oxidation of propionyl-CoA
propionyl-CoA
Carboxylase (biotin)
Epimerase
Mutase (VB12)
succinyl-CoA
O
CH3
C S CoA
HSCoA
CH3
2 Acetyl-CoA
C S CoA
thiolase
O
CH3
C CH2 C S CoA
Acetoacetyl-CoA
HMG-CoA
synthase
OH
OH
CH3
OOC CH2
CH CH2 COO
HSCoA
O
C CH2 C S CoA
CH3
-Hydroxy--methylglutaryl-CoA
HMG-CoA
-Hydroxy-butyrate
NAD+
-hydroxybutyrate
dehydrogenase
NADH+H+
HMG-CoA
lyase
Acetyl-CoA
CH3 C CH3
Acetone
Acetyl-CoA
CH3
CO2
C CH2 COO
Acetoacetate
HSCoA
ATP
AMP
PPi
Acetoacetate
thiokinase
Biological Significance
Ketone bodies replace glucose as the
major source of energy for many
tissues especially the brain, heart and
muscles during times of prolonged
starvation.
2.2 Lipogenesis
palmitoylCoA
O
C-S-CoA
H3C
stearic acid (C18:0)
stearoylCoA
O
C-S-CoA
9
oleic acid (C18:1 9)
18
H3 C
1
oleoylCoA
Citrate-pyruvate cycle
Process of synthesis:
(1) Carboxylation of Acetyl CoA
(2) Repetitive steps catalyzed by fatty
acid synthase
ATP
ADP + Pi
biotin
acetyl-CoA
carboxylase
O
OOC CH2 C SCoA
malonyl-CoA
glucagon
ATP
insulin
ADP + Pi
acetyl-CoA + HCO3 + H+
malonyl-CoA
acetyl-CoA carboxylase
(biotin)
long chain acyl-CoA
citrate
isocitrate
2. Elongation of palmitate
Elongation beyond the 16-C length of
the palmitate occurs in mitochondria
and endoplasmic reticulum (ER).
2.2.2
Synthesis of Triacylglycerol
Monoacylglycerol pathway (small
intestine)
Diacylglycerol pathway (liver, adipose
tissue)
1. Monoacylglycerol pathway
O
CH2
HSCoA
OH acyl CoA
R2 C O C H
CH2
OH
acyl CoA
transferase
O
O
CH2
R2 C O C H
CH2
acyl CoA
transferase
C R1
OH
1,2-diacylglycerol
2-monoacylglycerol
HSCoA
acyl CoA
CH2 O C R1
R2 C O C H
CH2 O C R3
triacylglycerol
2. Diacylglycerol pathway
glycolysis
Summary
Places:
tissue
Materials:
Endogenous: glucose amino acid
glycerol
Exogenous: free fatty acid and
monoacylglycerol
Work
or
Growth
fatty acids
& triacylglcerols
ADP
ATP
Heat
CO2 + H2O
Obesity
Section 3 Metabolism of
Phospholipids
glycerol
fatty acids
nitrogenous base
Phosphatidylcholine
glycerol
CH2 O
O
R2
C
CH2
R1
fatty
acyl group
O
O
O X Nitrogenous
base
OH
In general, glycerophospholipids
contain a saturated fatty acid at C-1 and
an unsaturated fatty acid (usually
arachidonic acid) at C-2.
The major
function of
phospholipids
is to form
biomembrane.
3.2
Synthesis of Glycerophospholipid
Location:
All tissue of body, especially liver &
kidney
Endoplasmic reticulum
Pathways:
CDP-diacylglycerol pathway
Diacylglycerol pathway
from carbohydrate
d. ATP, CTP
e. Enzymes and cofactors
Diacylglycerol pathway
CO2
HO CH2 CH COOH
3 SAM
Choline
Ethanolamine
NH2
Serine
ATP
ATP
ADP
ADP
Phosphocholine
Phosphoethanolamine
CTP
CTP
PPi
PPi
CDP-choline
CDP-ethanolamine
CO2
Phosphatidyl
serine
DG
DG
CMP
CMP
Phosphatidyl
ethanolamine
3 SAM
Phosphatidyl
choline
CDP-Diacylglycerol pathway
Dihydroxyacetone
phosphate
Glycerol 3-phosphate
Phosphotidate
CTP
PPi
Inositol
CMP
CDP-diacylglycerol
Serine
Phosphatidyl glycerol
CMP
CMP
Phosphatidyl inositol
Diphosphatidyl glycerol
(cardiolipin)
Phosphatidyl serine
Phosphatidylcholine (Lecithin)
Phosphatidylethanolamine (Cephalin)
CDP-diacylglycerol
Phosphatidylserine
Phosphatidylglycerol
Diphosphatidyl glycerol
(Cardiolipin)
Phosphatidylinositol
3.3 Degradation of
glycerophospholipids by
phospholipase
A1
O
A2
O
R2
CH2
C
CH2
R1
D
O
O
P
OH
C
O
O
CH2
HO
C
CH2
R1
R2
B1 O
O
OH
Lysophospholipid-1
OH
CH2
O
O
B2
C
CH2
O
O
P
OH
Lysophospholipid-2
Actions of phospholipases on
lecithin
PLA1: fatty acid + lysolecithin
PLA2: fatty acid + acyl
glycerophosphoryl choline
PLC: 1,2 diacylglycerol + phosphoryl
choline
PLD: phosphatidic acid + choline
O
O
R2
CH2
O
O C
CH2O
P
O
phospholipid
R1 H2O
R2
O
O
CH2
HO
O X
PLA2
O
H
CH2O
R1
O X
O
Lysophospholipid
Section 4 Metabolism of
Cholesterol
cholesterol
1. Function of cholesterol:
(1) It is a constituent of all cell
membranes.
(2) It is necessary for the synthesis of all
steroid hormones, bile salts and
vitamin D.
2. Structure of cholesterol
All steroids have cyclopentano penhydro
phenanthrene ring system.
H3C 21
18 CH3
19 CH3
2
3
HO
A
4
10
5
11
12
B 8
6
13
14
20
22
23
24
25
CH3
27 CH3
17
D 16
15
26
Cholesterol ester
O
R
Acetyl-CoA
HMG-CoA
Acetoacetyl-CoA
fasting
HMG CoA
Glucagon
after meal
insulin
MVA
thyroxine
cholesterol
bile acid
Vitamin D
Cholesterol
Primary bile
acids
Secondary
bile acids
Free bile
acids
Cholic acid
Glycocholic
acid
Taurocholic acid
Chenodeoxycholic acid
Glycochenodeoxycholic
acid
Taurochenodeoxycholic acid
Deoxycholic
acid
Glycodeoxycholic acid
Taurodeoxycholic acid
Lithocholic
acid
Glycolithocholic acid
Taurolitho-cholic
acid
COOH
COOH
12
HO
H
cholic acid
OH
OH
HO
OH
glycocholic acid
HO
OH
H
chenodeoxycholic acid
CONHCH2COOH
HO
OH
CONHCH2CH2SO3H
OH
taurocholic acid
OH
HO
H
deoxycholic acid
COOH
COOH
HO
H
lithocholic acid
cholesterol
in skin
25-hydroxylase
(microsome
in the liver)
ultraviolet
light
7-dehydrocholecalciferol (VD3)
cholesterol
25-OH-D3
1-hydroxylase
(mitochondria
in the kidney)
1,25-(OH)2-D3
active Vit D3
HO
cholesterol
acyl CoA
cholesterol R C O
acyl transferase
cholesteryl ester
(ACAT)
in plasma
Section 5
Plasma lipoprotein
TG
cholesterol
blood lipids
free
ester
lecithin
phospholipids sphingolipids
cephalin
FFA
fast
slow
electron microscope
5.3 Structure
VLDL
LDL
HDL
<1.006
0.951.006
1.0061.063
1.0631.210
Protein
10
23
55
Phospholipids
18
20
24
Cholesterol
Cholesteryl esters
12
37
15
TG
85
50
10
Density(g/ml)
5.5 Apolipoproteins
Functions of apolipoproteins
a . To combine and transport lipids.
b . To regulate lipoprotein metabolism.
apo A II activates hepatic lipase HL
apo A I activates LCAT
apo C II activates lipoprotein
lipase LPL
c. To recognize the lipoprotein receptors.
1. CM
Chylomicrons are formed in the
intestinal mucosal cells and secreted
into the lacteals of lymphatic system.
structure of CM
Cholesterol
Apolipoproteins
phospholipids
Triacylglycerols and
cholesteryl esters
Metabolic fate of CM
summary of CM
Site of formation: intestinal mucosal
cells
Function: transport exogenous TG
key E: LPL in blood
HL in liver
apoC is the activator of LPL
apo E and apo B-48 will be recognized
by the LRP receptor
2. VLDL
Very low density lipoproteins (VLDL)
are synthesized in the liver and
produce a turbidity in plasma.
Nascent
VLDL
Summary of VLDL
Formation site: liver
Function: VLDL carries endogenous
triglycerides from liver to peripheral
tissues for energy needs.
key E: LPL in blood
HL in liver
3. LDL
Most of the LDL particles are derived
from VLDL, but a small part is directly
released from liver. They are
cholesterol rich lipoprotein molecules
containing only apo B-100.
LDL
receptors
Cholesterol
ester
protein
Cholesterol
LDL
Cholesteryl
oleate
Amino acids
LDL binding
Internalization
Lysosomal hydrolysis
Summary of LDL
Formation site: from VLDL in blood
Function: transport cholesterol from
liver to the peripheral tissues. LDL
concentration in blood has positive
correlation with incidence of
cardiovascular diseases.
4. HDL
LDL variety is called bad cholesterol
whereas HDL is known as good
cholesterol .
Liver
Heart
VLDL
Good
Excretion
BAD
LDL
Cholesterol
Deposit
HDL
CETP
Cholesterol ester transfer protein
(CETP) transfer cholesterol ester in
HDL to VLDL and LDL.
Summary of HDL
Formation site: liver and intestine
Function: transport cholesterol from
peripheral tissues to liver
5.7 Hyperlipidemias
classification
Lipoprotein
Blood lipids
CM
TAG CH
LDL
CH
LDL, VLDL
CH TAG
IDL
CH TAG
VLDL
VLDL, CM
TAG
TAG CH