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60-150
90 %
(Triglycericle
1.
2.
emulsification
(bile acid
bile salt
mixed micelle
hydroprobic hydrophilic
amphipathic
cholecystokinin
cholecystokinin
(CCK)
( pancreatic
(pH
6)
.
Triglyceride mucosal intestinal villi
pancreatic lipase fatty acid C1 3 2-monoacylglycerol 2 fatty acid
.
pancreatic cholesterol ester
. phospholipase A2 lysophospholipase
Enz yme
Lipase
Pa nc rea ti c
Act iva ti on
bile lipids
Phospholipids
Co-lipase
Enz yme s
an d
Sub st at e
triacyglycerol
Di et ar y
Li pid s
/ .
Phospholipase A2
trypsin, Ca2+
phospholipid
Cholesteryl ester
hydrolase
bile salts
cholesteryl
triacylglycerol
phospholipid
cholesteryl ester
2monoacylglycerol
lyso-phospholipid
+
cholesterol
+
ester
fatty
fatty
acids
acids
acid
fatty
soluble
vitamins
( hydrophobic hydrophilic )
brush border membrane intestinal lumen short
medium chain (C4-C12)
portal blood albumin
bile salt 95 % enterohepatic circulation
(lipoprotein)
micelles
nonpolar
polar
(lipoprotein)
/ .
http://www.kumc.edu/research/medicine/biochemistry/bioc800/lip-lobj.htm)
chylomicron
Human
Plasma
Lipoprotein
Lipoprotein
Component
chylomicron
VLDL
class
IDL
LDL
HDL
18
31
6
22
22
25
4
9
42
22
43
2
5
20
30
Wt%
Apoprotein
Triacylglycerol
Cholesterol
Cholesteryl ester
Phospholipid
2
83
2
3
7
10
50
6
14
18
2
3
1.
2.
3.
(TG )
reesterification
(exogeneous
(exogeneous
triglycerides)
chylomicron
C-II
(ex og ene ou s
lipid)
lipid)
lipid)
lipi d)
chylomicron
fasting starvation
Chylomicron chylomicron remnent
(receptor) receptor Apoprotein E Chylomicron remnants
endocytosis lysosomal enzyme fatty acid, amino acid, glycerol, cholesterol
phosphate product triglyceride , bile salt, phospholipid , cholesterol
Glycerol triacylglycerol lipoprotein lipase glycerol-3-phosphate
glycolysis
gluconeogenesis
adipose tissue
(endogeneous
(storage
/ .
(TG)
(endogeneous
lipid)
(endogeneous triglycerides)
, B-100 , C E VLDL Fed state
TG lipoprotein lipase Apo-C lipoprotein lipase
VLDL free cholesterol phospholipid HDL Cholesterol ester
HDL IDL IDL LDL LDL receptor
lipoprotein
1.
HDL
ApoE,
apoCII
Chylomicron
VLDL
2. HDL Cholesterol lipoprotein , cell membrane Cholesterol ester
3. HDL cholesterol cholesterol ester cholesterol ester lipoprotein HDL
cholesterol cholesterol cholesterol
(atherosclerosis) LDL cholesterol
HDL
2 : TG
http://www.kumc.edu/research/medicine/biochemistry/bioc800/lip-lobj.htm)
re-esterification TG
glycerol-3-P glucose phosphtidic acid
1, 2 diacylglycerol
3 1, 2-diacyglycerol triglyceride glycerol-3-P
glycerol glycerokinase glycerol glycerol 3-P
TG
/ .
3 (TG) , glycerol-3-P
http://www.kumc.edu/research/medicine/biochemistry/bioc800/lip-lobj.htm)
TG glucose insulin
glycolysis glycerol-3-P acetyl CoA
VLDL
chylomicron
liproprotein
lipase
/ fatty acyl
CoA glycerol 3-P TG
glucose triglyceride
VLDL
TG
acetyl-CoA TG
http://www.kumc.edu/research/medicine/biochemistry/bioc800/lip-lobj.htm)
ac et yl
CoA
TG
/ .
6
,
cytosol
4
5
6
CH3-C-ScoA
Acetyl CoA
Fatty
CH3(CH2)14C-OH+7CO2+8CoASH+
ace ty l C
HOOC
palmi tic
CH3-C-ScoA
+
acid
14NADPH
molonyl
14
acid
H+
CoA
synthease
O
6H2O+14NADP+
oA
1.
amino
acid
cytoplasm
product
acetyl
CoA
2. oxidation fatty acid mitochondria acetyl CoA Cytosol citrate (acetyl CoA +
oxaloacetate) acetyl mitochondria membrane citrate mitochrondria
cytosol ATP ATP isocitrate
dehydrogenase TCA cycle citrate mitochondria cytosol acetyl CoA
oxaloacetat3. glucose glycolysis cytoplasm pyruvate mitochondria acetyl
CoA
pyruvate
dehydrogenase
citrate
cytosol
/ .
7
NA DPH
1.
2.
HMS
pathway
NADH
NADPH
malate
pyruvate
Acetyl
CoA
(
http://www.kumc.edu/research/medicine/biochemistry/bioc800/lip-lobj.htm)
16 C (palmitic acid) palmitic acid
2 ER mitochrondria chain
elongation hydrogen Desaturation
Desaturation
palmitic acid
Elongation
( http://www.kumc.edu/research/medicine/biochemistry/bioc800/lip-lobj.htm)
TG
(fasting
albumin
state) ,
TG
(starvation)
-oxidation
-oxidation
/ .
glucogon
TG
epinephrine, norepinephrine,
glycerol 3
http://www.kumc.edu/research/medicine/biochemistry/bioc800/lip-lobj.htm)
-o xi dat ion
-oxidation
-oxidation - oxidation
-o xi dat ion
-oxidation
mitochrondria
- 2 COOH Aceyl CoA (n-2) Acetyl CoA
- Acetyl CoA TCA cycle ATP
- NADH, FADH electron transport system ATP
acetyl
-oxidation pathway
CoA
(activation)
synthase
-o xi dat ion
, ATP
O
RCH2CH2COOH + ATP + CoASH
RCH2CH2-C-SCOA + AMP + Pi
Acyl CoA
(acyl CoA)
synthase
inner mitochondria membrane metrix carnitine carnitine shutle
/ .
CoA)
-oxidation
4
2
1.
trans-enoyl acyl CoA acyl CoA dehydrogenase FAD
2. 2 trans-enoyl acyl CoA (hydration) enoyl hydratase
2
L- hydroxyacyl CoA
3. L-
hydroxyacyl
CoA
L-
hydroxyacyl
CoA
dehydrogenase
-ketoacyl
CoA
4. -ketoacyl CoA thiolase acetyl CoA acyl CoA
(Acyl
-oxidation
(
http://www.kumc.edu/research/medicine/biochemistry/bioc800/lip-lobj.htm)
acyl CoA -oxidation 2 acetyl CoA
acetyl
CoA
ATP
-
2
ATP
FADH2
1
electron
transport
chain
-
3
ATP
NADH
1
electron
transport
chain
-
12
ATP
acetyl
CoA
1
TCA
cycle
-
ATP
acyl
CoA
palmitic -oxidation
O
C16H31O2
8 CH3-C-ScoA + 7 FADH2 + 7 NADH + 7H+
/ .
10
O
8 CH3-C-ScoA TCA cycle
7 FADH2 electron transport
7 NADH eletron transport
ATP
ATP
12x8
=
2x7
3x7
=
96
=
=
-2
=
ATP
14
21
ATP
129
ATP
ATP
ATP
CH3(CH2)7 CH=CHCH2
-oxidation
CH2
CH2
C H2
-oxidation
CH3(CH2)6
O
CH=CH-C
SCoA
Phospholipid
CH2CH2
4
4FADH2
glycerophospholipids
acyl CoA
4NADH +
4H
O
4CH3-C-ScoA
2 acyl CoA
( 1) FAD Acyl CoA
enoyl hydratase enoyl hydratase hydration -oxidation 5 acetyl CoA
+
NADH, + H FADH2 dehydrogenation -oxidation
acetyl CoA = [(9x12) + (7x2) + (8x3) 2] = 144 ATP
COOH
(18:1 -9)
CH2
COOH
sphingolipid
Glycerophosphplipid
lung surfactant eicosanoid ether glycerophoshpolipid
plasmalogen, platelet activating factor Triacylglycerol
choline, ethanolamine, serine inositol
CDP-diacylglycerol
/ .
11
phosphatidic
acid
phospholipid
http://www.kumc.edu/research/medicine/biochemistry/bioc800/lip-lobj.htm)
Sphingosine
10
sphingomyelin
Sphingosine 2
Ceramide
Sphingolipids
http://www.kumc.edu/research/medicine/biochemistry/bioc800/lip-lobj.htm)
lipoproteins
acetyl CoA
glucose,
fatty
acid
acetyl CoA 2 Acetoacetyl CoA acetyl CoA
3-hydroxy-3-methyglutaryl CoA (HMG CoA) HMG CoA mevalonate HMG CoA
reductase
isoprene
27
Major
Stage
acids
Stages
3 acetyl-CoA
Stage
2.
5 mevalonate
Stage
3.
Squalene
amino
in
1.
Formation
the
Biosynthesis
mevalonate
of
isoprene
squalene
Cyclization
lanosterol
of
unit
+
&
Cholesterol
Condensation
+
3CoA
of
Polymerization
5
CO2
Transformation
/ .
12
Lanosterol
cholesterol
CO2
HCOO
HMG
(artherosclerosis)
CoA reductase
acetyl CoA
ketone bodies (acetoacetate, 3-hydroxybotyrate acetone) acetyl
CoA
Oxidized
ketone
bodies
1
ketone bodies ketone
bodies ketonemia ketonuria
ketone
bodies
1.
lipoprotein
albumin
2. acetyl CoA oxidative
3.Extrahepatic tissue skeletal, cardiac muscle, renal cortex
11
acetyl CoA
http://www.kumc.edu/research/medicine/biochemistry/bioc800/lip-lobj.htm)
(Hyperchylomicronemia)
medium
chain
chylomicron
triglyceride
chylomicron
chylomicron
/ .
13
(fatty
liver)
lipoprotein
VLDL choline
phosphoglyceride phospholipid
methionine
VLDL
NADH
acetyl
CoA
NADH
chain fatty
VLDL
long
acid
(Obesity)
acetyl
CoA
Diabetic
ketosis
ketosis
Myrray RK,Granner DK, Mayes PA, Rodwell VW. Harper's biochemistry. 24 th ed. New Jersey: Prentice Hall
International Inc., 1996.
2. Voet D, Parson WW, Vance DE. Principles of biochemistry. Oxford: Wm.C. Brown Publishers, 1995.
nd
3. Mathews CR, Van Holde KE. Biochemistry. 2 ed. Puerto Rico: The Benjamin/Cummings Publishing Company
Inc,1996
4. Marks DB, Marks AD, Smith CM. Basic medical biochemistry : A clinical approach. Baltimore, Maryland :
Williams& Wilkins, 1996.
5. (http://www.kumc.edu/research/medicine/biochemistry/bioc800/lip-lobj.htm)
6. . :
7. . : ,. : .2536
1.
14
/ .