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Chapter 5
lipids metabolism
LIPIDS
• Water-insoluble substances that can be
extracted from cells by nonpolar organic
solvents
• Characteristics of fat
• Hydrophobic because of nonpolar FA chain
• Lipids store large amounts of energy
• 9 kcal/gram due to energy rich fatty acid chain
Outline
•
•
•
•
•
•
Classification of FA and Nomenclature
Digestion of Triacylglycerols
Metabolism of TAG
Metabolism of phospholipids
Metabolism of cholesterol
Lipoproteins metabolism
Section 1
Classification of FA and Nomenclature（命名）
• According to the number of carbon atom:
short chain(2~4C), medium chain (6~10C) & long
chain(12~26C) fatty acid
• According to whether it contains double bond or not
(saturate & unsaturate fatty acid)
• According to the number of carbon atom, the source &
property. such as: Butyric acid, Arachidonic acid
• systemic nomination
( catalogue,  or n catalogue)
Classification and Functions of Lipids
1. Triglyceride, TG（Variable lipids）:
- As storage and transport form of metabolic fuel
- To keep the body temperature
- Fats are solids; oils are liquids
- To protect the visceras
2. Lipoid（Basic lipids）：Cholesterols, Phospholipids,
Glycolipids et al
- As structural components of biological membranes.
- Cholesterol serves the precursor of bile salt and
steroid hormones
3. Lipid ramification: to involve the different functions
Fatty Acids
Acids obtained by the hydrolysis of fats and oils
• Saturated (have only single bonds)
• Unsaturated (have double bonds)
• Essential
-must originate from dietary sources
-the body cannot synthesize
-Polyunsaturated fatty acids
linoleic :(18:2,9,12)
linoleinic:(18:3, 9,12,15)
arachidonic acid :(20:4, 5,8,11,14)
Omega-3 / Omega-6 Fatty Acids
– Sources of omega-3 fatty • Sources of omega-6
acid: soybean,
fatty acids
salmon……
– Vegetable oils
– Eicosapentaenoic
– Nuts and seeds
acid(EPA,fish oil): found
in oils of shell fish, coldwater tuna, sardines, and
sea mammals
Triglyceride
Triglycerides（triacylglycerols）,Called “Neutral Fats”
- made of 3 free fatty acids and 1 glycerol
- FFA 4-22 Carbons long (mostly 16-20)
- 95% of dietary lipids (fats & oils)
Glycerol + 3 FFA
TG + H2O
Section 2
Digestion of Triacylglycerols
6 Steps of Digestion and absorption of lipids
Minor digestion of triacylglycerols in mouth and stomach by lingual lipase
Major digestion of all lipids in the lumen of the duodenum(十二指肠) / jejunum
（空肠）by Pancreatic lipases
Bile acid facilitated formation of mixed micelles that present the lipolytic products
to the mucosal surface, followed later by enterohepatic（肠肝）bile acid recycling
Passive absorption of the lipolytic products from the mixed micelle into the
intestinal epithelial cell，Glycerol & FAs < 12 carbons in length pass thru the cell
into the blood without modification. 2-monacylglycerols and FAs > 12 carbons in
length are re-synthesized into TGs in the endoplasmic reticulum TGs then form
large lipid globules in the ER called nascent chylomicrons （乳糜微粒）”.Several
apolipoproteins are required
Re-esterification of 2-monoacylglycerol, lysolecithin（溶血卵磷脂）, and
cholesterol with free fatty acids inside the intestinal enterocyte
Assembly and export from intestinal cells to the lymphatics of chylomicrons coated
with Apo B48 and containing triacylglycerols, cholesterol esters and phospholipids
Section 3
Metabolism of TAG
1. Synthesis of TAG
2. Catabolism of TAG
- Fatty acid bata oxidation
-Ketogenesis and Ketone Bodies
3. Lipogenesis: Fatty Acid Synthesis
4. Some poly-unsaturated FA ramification
The synthesis of TAG
1. Mono-acylglycerol pathway (MAG pathway)
(for dietary fat digestion and absorption)
CH 2OCOR
CHOCOR
CH 2OCOR
TAG
pancreatic
lipase
FA
CH 2OCOR
CHOCOR
pancreatic
lipase
CH 2OH
DAG
FA
CH 2OH
CHOCOR
CH 2OH
MAG
intestinal lumen
FA
FA
ATP,CoA
acyl CoA
acyl CoA
CH 2OH
CHOCOR
CH 2OCOR
CHOCOR
CH 2OH
MAG
intestinal epithelium
CH 2OCOR
TAG
lymphatic vessels
Chylomicrons
adipose tissue
2. Diacylglycerol pathway (DAG pathway)
(for TAG synthesis of in adipose tissue, liver and kidney)
glucose
CH 2OH
liver
adipose tissue
CO
NADH+H +
liver
kidney
NAD+ CH2OH
ADP
ATP
CH 2OH
CHOH
CHOH
phosphoglycerol
glycerol kinase
dehydrogenase
CH 2O-PO 3H2
CH 2OH
CH 2O-PO 3H2
dihydroxyacetone
phosphate
glycerol
3-phosphoglycerol
RCO¡« SCoA
acyl CoA transferase
HSCoA
CH2OCOR
HSCoA RCO¡« SCoACH2OCOR
CHOCOR
CH2OCOR
triacylglycerol
CHOCOR
Pi
H2O
CH 2OCOR
HSCoA RCO¡« SCoA
CHOH
CHOCOR
CH 2OH
phosphatase CH2O-PO 3H2
acyl CoA
transferase diacylglycerol
phosphatidate
CH 2OCOR
acyl CoA
transferase
CH 2O-PO 3H2
lysophosphatidate
Catabolism of TAG
Mobilization of triacylglycerols
Mobilization of triacylglycerols:
in the adipose tissue, breaks
down triacylglycerols to free
fatty acids and glycerol (fatty
acids are hydrolyzed initially
from C1or C3 of the fat)
hormone sensitive lipase
cleave a fatty acid from a
triglyceride, then other lipase
complete the process of lipolysis,
and fatty acid are released into
the blood by serum albumin
• The glycerol is absorbed by the liver and
converted to glycolytic intermediates
Fatty acid bata oxidation
CAPILLARY
lipoproteins
MITOCHONDRION
FABP
FA
LPL
FA
FA
albumin
FA
1
3
FA
TCA
cycle 7
-oxidation
6
acyl-CoA
acetyl-CoA
2
FA
FABP
4
acyl-CoA
FABP
CYTOPLASM
A
C
S
5
carnitine
transporter
From fat cell
cell membrane
FA = fatty acid
LPL = lipoprotein lipase
FABP = fatty acid binding protein
ACS = acyl CoA synthetase
Overview of fatty acid degradation
Steps in Beta Oxidation
• Fatty Acid Activation by esterification with
CoASH
• Membrane Transport of Fatty Acyl CoA Esters
• ***Carbon Backbone Reaction Sequence
•
•
•
•
Dehydrogenation
Hydration
Dehydrogenation
Thiolase Reaction (Carbon-Carbon Cleavage)
1. Activation of Fatty Acids
• Acyl CoA synthetase reaction occurs on the
mitochondrial membrane
2.Transport into Mitochondrial Matrix
• Carnitine carries
long-chain
activated fatty
acids into the
mitochondrial
matrix
• Carnitine carries long-chain activated fatty
acids into the mitochondrial matrix
3. Fatty acid Beta oxidation
• Each round in fatty
acid degradation
involves four reactions
– 1. oxidation to
trans-∆2-Enoly-CoA
Removes H atoms from the
 and  carbons
-Forms a trans C=C bond
-Reduces FAD to FADH2
 
2. Hydration to L–3–
Hydroxylacyl CoA
– Adds water across the
trans C=C bond
– Forms a hydroxyl group
(—OH) on the  carbon
3. Oxidation to
– 3–Ketoacyl CoA
– Oxidizes the hydroxyl
group
– Forms a keto group on the
 carbon
4. Thiolysis to produce
Acetyl–CoA
– acetyl CoA is cleaved:By
splitting the bond between the
 and  carbons.
– To form a shortened fatty acyl
CoA that repeats steps 1 - 4 of
-oxidation
-Oxidation of Myristic(C14) Acid
-Oxidation of Myristic (C14) Acid
6 cycles
7 Acetyl
CoA
Cycles of -Oxidation
The length of a fatty acid
• Determines the number of oxidations and the
total number of acetyl CoA groups
Carbons in
Acetyl CoA -Oxidation Cycles
Fatty Acid
(C/2)
(C/2 –1)
12
6
5
14
7
6
16
8
7
18
9
8
-Oxidation and ATP
Activation of a fatty acid requires:
2 ATP
One cycle of oxidation of a fatty acid produces:
1 NADH
3 ATP
1 FADH2
2 ATP
Acetyl CoA entering the citric acid cycle produces:
1 Acetyl CoA
12 ATP
ATP for Myristic Acid C14
ATP production for Myristic(14 carbons):
Activation of myristic acid
7 Acetyl CoA
7 acetyl CoA x 12 ATP/acetyl CoA
6 Oxidation cycles
6 NADH x 3ATP/NADH
6 FADH2 x 2ATP/FADH2
Total
-2 ATP
84 ATP
18 ATP
12 ATP
102 ATP
Oxidation of Special Cases
(monounsaturated fatty acids)
Odd Carbon Fatty Acids
CH3CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2CH2--CH2COSCoA
5 Cycles
5 CH3COSCoA + CH3CH2COSCoA
Propionyl CoA
TCA Cycle
CO2 H
Mutase
CH3 -C-H
HO 2CCH2CH2COSCoA
Succinyl CoA
Epimerase
Vit. B12
COSCoA
L-Methylmalonyl
CoA
Propionyl CoA
Carboxylase
ATP/CO2
CO2H
H-C-CH3
COSCoA
D-Methylmalonyl
CoA
Ketogenesis (Ketosis):
formation of Ketone Bodies *****
Thiolase
2 CH3COSCoA
CH3COSCoA
CH3COCH2COSCoA
Acetoacetyl CoA
HMG CoA
Synthase
Cholesterol
(in cytosol)
Several
steps
OH
HO2C-CH2-C-CH2COSCoA
(in liver: mitochondrial matrix)
CH3
Ketogenesis
-Hydroxy- -methylglutaryl CoA
(HMG CoA)
Ketogenesis: formation of Ketone Bodies
OH
HO2C-CH2-C-CH2COSCoA
CH3
HMG CoA
HMG CoA
lyase
CH3COCH2CO2H
Acetoacetic Acid
- CH3COSCoA
+
NADH + H
Dehydrogenase
+
NAD
OH
CH3CHCH2CO2H
-Hydroxybutyrate
- CO2
CH3COCH3
Acetone
(volatile)
Ketone bodies are important sources of energy, especially in starvation
Oxidation of ketone bodies
in brain, muscle, kidney, and intestine
NAD+
NADH
-Hydroxybutyrate
Succinyl CoA synthetase = loss of GTP
Acetoacetate
Succinyl CoA
-Hydroxybutyrate
dehydrogenase
CoA transferase
CoA
Succinate
2 Acetyl CoA
Acetoacetyl CoA
Thiolase
Citric
Acid
Cycle
The significance
of ketogenesis and ketogenolysis
• Ketone bodies are water soluble, they are convenient to
transport in blood, and readily taken up by non-hepatic tissues
In the early stages of fasting, the use of ketone bodies by
heart, skeletal muscle conserves glucose for support of central
nervous system. With more prolonged starvation, brain can
take up more ketone bodies to spare glucose consumption
• High concentration of ketone bodies can induce ketonemia
and ketonuria, and even ketosis and acidosis
When carbohydrate catabolism is blocked by a disease of
diabetes mellitus or defect of sugar source, the blood
concentration of ketone bodies may increase,the patient may
suffer from ketosis and acidosis
Overview Catabolism of TAG
glycerol
TAG
¢Ù
FFAs
not in adipose tissue
and muscle
¢Ý
¢Ú
¦Â-oxidation
glycolysis
acetyl CoA
in liver
TCA
¢Û
Ketone bodies
¢Ü
extrahepatic
tissues
CO2 + H2O + energy
Lipogenesis:
Fatty Acid Synthesis
• Fatty acid are synthesized and degraded by different
pathways
– from acetyl CoA
– in the cytosol
– intermediates are attached to the acyl carrier
protein (ACP)
– the activated donor is malonyl–ACP
– reduction uses NADPH + H+
– stops at C16 (palmitic acid 软脂酸)
Reactivity of Coenzyme A
Nucleophilic acyl substitution
O
CH3CSCoA
HY ••
O
CH3C
Y •• + HSCoA
Acetyl coenzyme A is a source of an acetyl
group toward biological nucleophiles(it is an
acetyl transfer agent)
Reactivity of Coenzyme A
can react via enol(烯醇)
O
OH
H2C
CH3CSCoA
CSCoA
E+
Acetyl coenzyme A reacts with
biological electrophiles at its
carbon atom
E
O
CH2CSCoA
Formation of Malonyl Coenzyme A
Formation of malonyl–CoA is the committed
step in fatty acid synthesis
O
||
CH3—C—S—CoA + HCO3- + ATP
Acetyl CoA
O
O
||
||
-O—C—CH2—C—S—ACP + ADP + Pi
Malonyl (丙二酰) CoA
Formation of Acetyl and Malonyl ACP
• The intermediates(acetyl-ACP and malonyl-ACP) in
fatty acid synthesis are covalently linked to the acyl
carrier protein (ACP)
In bacteria the enzymes that are involved in elongation are
separate proteins
In higher organisms the activities all reside on the same
polypeptide
– To start an elongation cycle, Acetyl–CoA and Malonyl–CoA
are each transferred to an acyl carrier protein
O
||
CH3—C—S—ACP ( Acetyl-ACP)
O
O
||
||
-O—C—CH2—C—S—ACP (Malonyl-ACP)
Condensation and Reduction
In reactions 1 and 2 of fatty
acid synthesis:
• Condensation by a synthase
combines acetyl-ACP with
malonyl-ACP to form
acetoacetyl-ACP (4C) and
CO2 (reaction 1)
• Reduction converts a ketone
to an alcohol using NADPH
(reaction 2)
Dehydration and Reduction
In reactions 3 and 4 of
fatty acid synthesis:
• Dehydration forms a
trans double bond
(reaction 3)
• Reduction converts the
double bond to a single
bond using NADPH
(Reaction 4)
Lipogenesis Cycle Repeats
Fatty acid synthesis
continues:
• Malonyl-ACP combines
with the four-carbon
butyryl-ACP to form a
six-carbon-ACP.
• The carbon chain
lengthens by two carbons
each cycle
Lipogenesis Cycle Completed
• Fatty acid synthesis
is completed when
palmitoyl ACP reacts
with water to give
palmitate (C16) and
free ACP.
Summary of Lipogenesis
Elongation and Unsaturation
• Endoplasmic reticulum(内质网) systems introduce
double bonds into long chain acyl–CoA's
– Reaction combines both NADH and the acyl–
CoA's to reduce O2 to H2O
• convert palmitoyl–CoA to other fatty acids
– Reactions occur on the cytosolic face of the
endoplasmic reticulum.
– Malonyl–CoA is the donor in elongation reactions
 Oxidation and Fatty Acid Synthesis
Fatty Acid Formation
• Shorter fatty acids undergo fewer cycles
• Longer fatty acids are produced from palmitate
using special enzymes
• Unsaturated cis bonds are incorporated into a 10carbon fatty acid that is elongated further
• When blood glucose is high, insulin stimulates
glycolysis and pyruvate oxidation to obtain acetyl
CoA to form fatty acids
Stoichiometry of FA synthesis
• The stoichiometry of palmitate synthesis:
– Synythesis of palmitate from Malonyl–CoA
– Synthesis of Malonyl–CoA from Acetyl–CoA
– Overall synthesis
Sources of NADPH
• The malate dehydrogenase and NADP+–linked malate
enzyme reactions of the citrate shuttle exchange
NADH for NADPH
Citrate Shuttle
• Acetyl–CoA is synthesized in the mitochondrial matrix,
whereas fatty acids are synthesized in the cytosol
– Acetyl–CoA units are shuttled out of the mitochondrial matrix as citrate:
Regulation of Fatty Acid Synthesis
• Regulation of Acetyl
carboxylase（乙酰羧化酶）
– Global
（+） insulin
（-） glucagon
（-） epinephrine
– Local
（+）Citrate
（-） Palmitoyl–CoA
（-） AMP
Eicosanoid Hormones（花生四烯酸类激素）
• Eicosanoid horomones are synthesized from
arachadonic acid (20:4，二十碳-四烯酸)
– Prostaglandins（前列腺素）
• 20-carbon fatty acid containing 5-carbon ring
• Prostacyclins
• Thromboxanes（血栓噁烷）
– Leukotrienes（白三烯）
• contain three conjugated double bonds
Eicosanoid Hormones
Eicosanoid Hormones
Section 4
Metabolism of phospholipids（磷脂）
Phospholipids
• Structure
– Glycerol + 2 fatty acids +
phosphate group
• Functions
– Component of cell
membranes
– Lipid transport as part of
lipoproteins
• Food sources
– Egg yolks, liver, soybeans,
peanuts
Phospholipids
• Phospholipids are intermediates in the
biosynthesis of triacylglycerols
• The starting materials are glycerol 3phosphate and the appropriate acyl
coenzyme A molecules
Biosynthesis of glycerophospholipids
HO-CH2-CH-COOH
NH2
serine
CO2
HO-CH2-CH2-NH2
ethanolamine
ATP
kinase
ADP
1. DAG shunt is the major pathway
for biosynthesis of phosphatidyl
choline (lecithin) and phosphatidyl
ethanolamine (cephalin)
3(S-adenosylmethionine)
+
HO-CH2-CH2-N(CH3)3
ATP choline
kinase
ADP
P -O-CH2-CH2-NH2
phosphoethanolamine
CTP
cytidyl transferase
PPi
CDP-O-CH2-CH2-NH2
CDP-ethanolamine
R2
+
-O-CH
-CH
P
2
2-N(CH3)3
phosphocholine
CTP
DAG O
cytidyl transferase
H 2C O C R 1
PPi
O
C O C H
CDP -O-CH2-CH2-N(CH3)3
CDP-choline
H C OH
2
diacylglycerol transferase
CMP
CMP
phosphatidyl ethanolamine (PE)
phosphatidyl choline (PC)
glucose
CDP-DAG shunt
glycerol 3-phosphate
2 acyl CoA
2. CDP-DAG shunt is the
major pathway for the
synthesis of phosphatidyl
serine, phosphatidyl
inositol and cardiolipin
- in this pathway, DAG is
activated as the form of
CDP-DAG
2 CoA
Phosphatidic acid
CTP
PPi
CDP-diacylglycerol
serine
phosphatidyl glycerol
inositol
CMP
CMP
CMP
diphosphatidyl glycerol
(cardiolipin)
phosphatidyl inositol
phosphatidyl serine
O
CH 2 O
O
R2
C
O
CH
CH 2 O
O
C R1 H2C
O
P
O-
O
HO C
O
H
P
O
O
CH 2
O
-
CH
O
C
R3
O
CH 2
CH 2
O
Cardiolipin (diphosphatidylglycerol)
C
R4
Degradation of glycerophospholipids
O
H 2C O C
R2
O
H2C O C
R1
O
C O C H
R2
O
O P
_
H2C OH
O
_
diglyceride
O
C O C H
O
P
H2C O
X
_
XOH
O
OH
O
phosphatidic acid
H2O
phospholipase C
O
H2C O C
R2
R1
O
C O C H
O
H2C O P
_
H2O
phospholipase D
R1
glycerophospholipid
O
X
O
phospholipase A1
H2C OH
R2
O
C O C H
O
H2C O P
_
lysophospholipid 2
R1
O
O
phospholipase B2
phospholipase A2
H2O
H2O
O
C OH
O
C OH
R2
O
H 2C O C
HO C H
X
H2O
H2O
R2
O
O
C OH R1 C OH
O
H 2C O P
_
R1
lysophospholipid 1
O
O
phospholipase B1
H2C OH
HO C H
O
H2C O P
_
O
O
X
(glycerophophocholine)
X
Metabolism of sphingolipids
O
( CH2)1 2 C H
CH
CH
CH
OH
NH
sphingosine
鞘氨醇
C H2
O
P
O
C H2
CH 2
+
N
H3 C
( CH3)3
O
C
phosphate
O
choline
R
fatty acid
The structure of phosphosphingolipids
H3C
(CH 2)1 2 C H
sphingosine
CH
CH
CH
OH
NH
C
C H2
O
Sphingolipids are a class of
lipids containing sphingosine
instead of glycerol
include: glycosphingolipids
phosphosphingolipids
x = monosaccharide cerebroside
X
sugar
O
x = sulfated galactose
( = cerebroside sulfate)
sulfatide
脑苷脂
硫酸脑苷脂
globoside 红细胞糖苷脂
x = oligosaccharide + sialic acid ganglioside
x = oligosaccharide
R
fatty acid
The structure of glycosphosphingolipids
神经节苷脂
note: sialic acid = N-acetylneuraminic acid
唾液酸
N-乙酰神经氨酸
Section 5
Metabolism of cholesterol
Structure of Cholesterol
12
11
19
C 13
1
2
A
3
4
10
5
18
14
9
B8
17
16 Fundamental framework of steroids
D
15
CH3
CH3
7
CH3
6
CH3
H
HO
CH3
H
H
Structure of Cholesterol
Cholesterol Biosynthesis
1. Formation of Mevalonate
Liver is primary site of cholesterol biosynthesis
Thiolase
2 CH3COSCoA
CH3COCH2COSCoA
CH3COSCoA
Acetoacetyl CoA
HMG CoA
Synthase
OH
HMGCoA
reductase
HO2C-CH2-C-CH2CH2OH
CH3
3R-Mevalonic acid
甲羟戊酸
CoASH
OH
HO2C-CH2-C-CH2COSCoA
NADP + NADPH
+H +
Key control step
CH3
-Hydroxy-bata-methylglutaryl CoA (HMG CoA)
Cholesterol Biosynthesis
2. processing of Squalene
OH
-O C-CH -C-CH CH OH
2
2
2
2
CH3
Mevalonate
OH
2 Steps
-O C-CH -C-CH CH OPOP
2
2
2
2
ATP
CH3
5-Pyrophospho(焦磷酸)mevalonate
- CO2
- H2 O
CH3
Isomerase
CH3-C=CH2CH2OPOP
Dimethylallyl
pyrophosphate
CH2=C-CH2CH2OPOP
Isopentenyl(异戊烯)
CH3
pyrophosphate
Isoprenoid（异戊二烯）Condensation
Dimethylallyl
pyrophosphate
Tail
Head to tail
Condensation
OPOP
Head
Tail
OPOP
Head
H
Head
OPOP
Tail
Geranyl (牛龙牛儿基)
Pyrophosphate (GPP)
Isopentenyl
Pyrophosphate (IPP)
Isoprenes异戊二烯
Tail to tail
condensation
of 2 FPPs
Head to tail
condensation
of IPP and GPP
OPOP
Squalene鲨烯
Head
Farnesyl（法尼基）
Pyrophosphate (FPP)
Tail
3. Conversion of Squalene to Cholesterol
Squalene2,3-epoxide
Squalene
monooxygenase
O2
Squalene鲨烯
O
H
2,3-Oxidosqualene:
lanosterol cyclase
+
CH3
CH3
CH3
CH3
20 Steps
CH3
HO
H3C
HO
Cholesterol
CH3
Lanosterol羊毛固醇
Transformations of Cholesterol
Cholesterol is the biosynthetic precursor to a
large number of important steroids:
Bile acids
Vitamin D3
Corticosteroids
Sex hormones
Section 6
Lipoproteins metabolism
General Features of Lipoproteins

Apolipoproteins: specific lipid-binding proteins that attach to the surface
intracellular recognition for exocytosis of the nascent particle after synthesis
activation of lipid-processing enzymes in the bloodstream,
binding to cell surface receptors for endocytosis and clearance

Main lipid components: triacylglycerols, cholesterol esters, phospholipids.

Major lipoproteins:
chylomicrons
very low density lipoproteins (VLDL)
low density lipoproteins (LDL)
high density lipoproteins (HDL)
_
_
origin ¦Ã
¦Â ¦Á 2
¦Á 1 A

Subfraction: intermediate density lipoproteins (IDL)

Electrophoretic mobility (charge):
Plasma lipoproteins
HDLs =  lipoproteins
LDLs = - lipoproteins
VLDLs = pre- lipoproteins (intermediate between  and  mobility)
CM
¦Â pre ¦Â ¦Á
Model of low density lipoprotein. Other lipoproteins have a similar
structure differing in the core content of lipid and the type of apoproteins on
the surface of the molecule
Functions of apolipoproteins
Protein
(Enzyme)
Site of
Action
Activator
Function
LPL (Enzyme)
capillary
walls
apo CII
excises FFA from TAGs in chylomicrons
and VLDLs for adipose and muscle
CERP
plasma
membrane
apo A1
(choles.
Induced)
flips cholesterol (and lecithin) to outer layer
of lipid bilayer for LCAT action in blood
Apo A1
blood,
plasma
membrane
none
activates LCAT and CERP; binds to apo A1
receptors on cells requiring cholesterol
extraction
Apo B48
Gut
none
export of chylomicrons from intestinal cells
Apo B100
Various cells
none
ligand for LDL receptor; export of liver
VLDL
Apo CII
capillary
walls
none
activates lipoprotein lipase
Apo E
liver
none
receptor ligand - clears remnants, IDL, and
HDL
composition of lipoproteins
Lipoprotein Total protein Total lipids
(%)
classes
(%)
CM
VLDL
1.5-2.5
97-99
Percent composition of lipid fractions
PL
ChE
Ch
TAG
7-9
3-5
1-3
84-98
(B,C-III,II,I)
5-10
90-95
15-20 10-15
5-10
50-65
75-80
15-20 35-40
7-10
7-10
4
5
(B,C-III,II,I)
LDL
20-25
(B)
HDL
40-45
(A-I)
55
35
12
intestine
Lymph system:
Chylomicrons
to capillaries
via lymph
chylomicron interacts
with lipoprotein lipase
removing FFA
Nascent chylomicrons acquire
apo CII (C) and E
(E) from HDL
non-hepatic tissues
CE
CE
CECE
CE
CECE
CE CE
ApoB48 aids with
chylomicron assembly
Chylomicrons carry dietary fatty acids to tissues
liver
Triacylglycerol
in core
Chylomicron (or VLDL)
To Liver
Apo CII
Lipoprotein lipase
Glycerol
Free fatty acids
Polysaccharide Chain
Capillary
Endothelial
Surface of cell
In cellulo (muscle & adipose)
Free fatty acids
Lipoprotein lipase action on chylomicron triacylglycerol
(an identical reaction occurs with VLDL)
Lymph system:
chylomicron interacts
with lipoprotein lipase
removing FFA
chylomicron
acquires apo
CII (C) and E
(E) from HDL
non-hepatic tissues
CE
CE
CECE
CE
CECE
CE CE
C
E
ApoB48
chylomicron
remnants lose
CII to HDL
E
C
E
E C
EE E
Liver: apo E receptor
takes up remnants to
deliver cholesterol
LIVER
Exogenous pathway of lipid transport
Chylomicrons carry dietary fatty acids to tissues and the remnants take cholesterol to the liver
B100 (B) helps
assemble and export
nascent VLDL
nascent VLDL acquires
apo CII (C) and apo E
(E) from HDL
LPL hydrolyze TAGs; FFA
uptake; LDL circulate to tissues
non-hepatic tissues
LIVER
CE
bile acids
Cholesterol
uptake;
excreted as
bile acids
Apo E binds
liver receptor
CE
CE CE
CE
CE
CE
CECE
B B
CE
CE
B
CII and E release to HDL
apo B100 on LDL bind
to receptor
B
B
B BB
B BB
LDL taken into the cell
to deliver cholesterol
HDL
scavenge
cholesterol
The liver-directed endogenous pathway of lipoprotein metabolism
Chylomicrons:
Exogenous Pathway
Chylomicron Processing and Interface with HDL
HDL: Both Pathways
B48
E
Nascent Chylomicron
Assembly in Gut
Mediated by B48
E
E
E B48 apo E & CII
CII
from HDL
Mature Chylomicron
Apo E and CII
added from HDL
E
CII activates LPL
A1
CII
E
CII
B48
CII
Nascent HDL
Assembled in liver
Loans apo E/ apo CII
to nascent chylomicrons
Lipoprotein Lipase
capillary walls
hydrolyzes TAG
deliver FFA into adipose/muscle
CII
CII
Chylomicron Remnant
from mature chylomicron
apo CII returned to HDL
adipose &
muscle
FFA
apo CII
A1
CII
E
B48
CII
CII
Triacylglycerol
Mature HDL
CE from peripheral cells
activated by apo A1
Apo CII returned by
chylomicrons
Cholesterol
ester
Phospholipid
VLDL/LDL Processing and Interface with HDL
VLDL/LDL:
Endogenous Pathway
HDL: Both Pathways
E
B100
Nascent VLDL
Assembly in Liver
Mediated by B100
E
A1
CII
apo CII & E
from HDL
Lipoprotein Lipase
capillary walls
hydrolyzes TAG
deliver FFA into adipose/muscle
B100
E
B100
CII
Mature VLDL
Apo E and CII
added from HDL
CII activates LPL
CII
adipose &
muscle
Mature HDL
Apo CII/E returned
by VLDL
A1
E
CII
FFA
apo
CII + E
CII
E
E
E
CII
LDL
from mature VLDL
B100
Clearance of Cholesterol by Liver from Chylomicron
Remnants, HDL and LDL
Chylomicron
Remnant
Mature
HDL
LDL
B100
B100
B100
E
Receptor
E
Receptor
CE Metabolism
B100
receptor
Bile acids
Consequence of Oxidized LDL Formation
LDL
Oxidation of LDL
Oxidized LDL
1. Uptake by "scavenger receptors" on
macrophages that invade artery walls;
become foam cells
2. Elicits CE deposition in artery walls
Atherosclerosis
动脉粥样硬化
LDL
receptor
sorting endosome:
ligand/receptor dissociation
lysosome
Golgi
late endosome
free pool of
cholesterol
ACEH
CE  cholesterol
ACAT (stimulated
by cholesterol)
endocytosis
Cholesterol release for
transport to liver
LDL
CE
CERP
Membrane
Cholesterol
Cholesterol metabolism to
bile acids or steroids
Apo A1 receptor
L
C
A
T
CE in nascent HDL
CE stored in
Cholesterol droplets
CE CE
Esterase
A1
Reverse
CholesterolTransport
A1
E
CII
E
CII
Apo A1 binds to receptor, activates
CERP to pump out cholesterol, and
LCAT to esterify cholesterol
Mature HDL:
Cleared by liver
Lipoprotein classes
Lipoprotein
Chylomicrons
VLDL
LDL
HDL
Source
gut
liver
Apo Proteins
B48, CII*, E*
B100, CII*, E*
blood B100
liver
A1, CII,
E("ACE")
Protein:Lipid/
Major (minor) Lipid
Transported
Function
1:49triacylglycerol (CE)
Dietary:
FFA  Adipose/muscle
CE  Liver via remnants
1:9 triacylglycerol (CE)
Synthesized:
FFA adipose/muscle
CE  LDL
1:3 cholesterol ester
1:1 cholesterol ester
CE to liver (70%) and
peripheral cells (30%)
supplies apo CII, E to
chylomicrons and VLDL;
mediates reverse
cholesterol transport
hypercholesterolemia
家族性高胆固醇血症表现
Guidelines for Appropriate Intake of Fat
☻ reduce fat in diet to <30%
☻ avoid saturated fat (animal fat)
☻ avoid margarine（奶油）, baked goods, fried food
☻ mono/polyunsaturated cooking oils are best (olive, corn)
☻ eat foods rich in -3 polyunsaturated fatty acids
(e.g, soybean，salmon)
选择题练习
脂代谢
1. 脂肪动员的限速酶是(
)
A 激素敏感性脂肪酶(HSL)
B 胰脂酶
C 脂蛋白脂肪酶
D 组织脂肪酶
E 辅脂酶
2.
下列不能促进脂肪动员的激素是(
A 胰高血糖素
B 肾上腺素
C ACTH
D 促甲状腺素
E 胰岛素
)
3. 下列物质在体内彻底氧化后,每克释放
能量最多的是(
)
A 葡萄糖
B 糖原
C 脂肪
D 胆固醇
E 蛋白质
4. 脂肪酸氧化分解的限速酶是(
A 脂酰CoA合成酶
B 肉碱脂酰转移酶I
C 肉碱脂酰转移酶II
D 脂酰CoA脱氢酶
E -羟脱氢酶
)
5. 脂肪酰进行-氧化的酶促反应顺序为(
A 脱氢,脱水,再脱氢,硫解
B 脱氢,加水,再脱氢,硫解
C 脱氢,再脱氢,加水, 硫解
D 硫解,脱氢,加水,再脱氢
E 缩合,还原,脱水,再还原
)
6. 严重饥饿时,脑组织的能量主要来源于(
A 糖的氧化
B 脂肪酸的氧化
C 氨基酸的氧化
D 乳酸氧化
E 酮体氧化
)
7. 通常生物膜中不存在的脂类是(
A 脑磷脂
B 卵磷脂
C 胆固醇
D 甘油三酯
E 糖脂
)
8. 下列关于HMG-CoA还原酶的叙述哪项事错误的(
A 此酶存在于细胞胞液中
B 是胆固醇合成过程中的限速酶
C 胰岛素可以诱导此酶合成
D 经磷酸化后活性可增强
E 胆固醇可反馈抑制其活性
)
9. 家族性高胆固醇血症纯合子的原发行代谢障碍是(
A 缺乏载脂蛋白B
B 由VLDL生成LDL增加
C 细胞膜LDL受体功能缺陷
D 肝脏HMG-CoA还原酶活性增加
E 脂酰胆固醇脂酰转移酶(ACAT)活性降低
)
10. 下列有关脂酸合成的叙述不正确的是(
)
A 脂肪酸合成酶系存在于胞液中
B 脂肪酸分子中全部碳原子来源于丙二酰CoA
C 生物素是辅助因子
D 消耗ATP
E 需要NADPH参与
11. The organ having the strongest ability of fatty
acid synthesis is ( )
A fatty tissue
B lacteal gland
C liver
D kidney
E brain
12. Which one transports cholesterol from
outer to inner of liver?
A CM
B VLDL
C LDL
D HDL
E IDL
13. Which one is essential fatty acid?
A palmitic acid
B stearic acid
C oleinic acid
D octadecadienoic acid
E eicosanoic acid
14. The main metabolic outlet of body cholesterol is (
A change into cholesterol ester
B change into vitamine D3
C change into bile acid
D change into steroid hormone
E change into dihydrocholesterol
)
15. 下列物质中与脂肪消化吸收有关的是(
A 胰脂酶
B 脂蛋白脂肪酶
C 激素敏感性脂肪酶
D 辅脂酶
E 胆酸
)
16. 合成甘油磷脂共同需要的原料有(
A 甘油
B 脂肪酸
C 胆碱
D 乙醇胺
E 磷酸盐
)
17. 参与血浆脂蛋白代谢的关键酶(
A 激素敏感性脂肪酶(HSL)
B 脂蛋白脂肪酶(LPL)
C 肝脂肪酶(HL)
D 卵磷脂胆固醇酰基转移酶(LCAT)
E 脂酰基胆固醇脂酰转移酶(ACAT)
)
18. 脂蛋白的结构是(
)
A 脂蛋白呈球状颗粒
B 脂蛋白具有亲水表面和疏水核心
C 载脂蛋白位于表面
D CM VLDL主要以甘油三酯为核心
E LDL HDL主要以胆固醇酯为核心
19. Which can be the source of acetyl CoA?
A glucose
B fatty acid
C ketone body
D cholesterol
E citric acid
20. The matters which join in synthesis of
cholesterol directly are ( )
A acetyl CoA
B malonyl CoA
C ATP
D NADH
E NADPH