??? ???? (Lipid Metabolism)

1
????
P230
??? ???? (Lipid Metabolism)
2
??? ??
P230

• 1.1?????????????
• ???????????
• ??????????????
• ?????????????

3
Triacylglycerols are ideal for Energy Storage

• Highly reduced more than twice as much energy as
  carbohydrates or proteins at equal weight
• Highly hydrophobic not raising osmolarity of
  cytosol, not adding extra weight
• Chemically inert no undesired chemical reactions
  with other constituents

4
1.2 ??????????

• 1.2.1 ???????
• ?? ? ???????
• ???????????
• ????????????????
• ?????????

• Bile salts (e.g., glycocholate????) emulsify the
  fats and form mixed micelles (??,??)
• Lipases degrade triacylglycerols
• Products diffuse into epithelial cells(????)
• Triacylglycerols reformed after absorption.

5
??????????????
??
????
6
1.2.2 ????????
???
b-????
????????
??????? (?????)
??
?????
????????????
7
1.2.3 ???????????
?????????????,????????????(????)????????????????
8
??? ???????Catabolism of fats

• Triacylglycerols

Glycerol Fatty acids
a-P-glycerol
??
Glyceraldehyde-3-P
Acetone body
EMP
Acetyl-CoA
Pyruvate
TCA
9
Triacylglycerols Present Problems for Being Used
as fuels

• Must be emulsified(??)
• Must be carried on special proteins in blood
  (i.e. serum albumin)
• Must be activated

10
2.1 ?????????
???
11
2.1.1 ???? (pancreatic lipase)

• ??????????
• ???????????
• ???????????
• ?????????C1?C3??

12
2.1.2 ?????????
13
2.2 ??????? (fate of glycerol)

• ????????????????,?????????
• 1. ???-P-glycerol,
  ????FA??FAT
• 2. ???-P-glycerol, ??DHAP,
  ????
• 3. ???-P-glycerol,
  ??DHAP,????
• 
  ?? ?

?-P-glycerol
14
2.2 ??????? (fate of glycerol)
15
2.3 ????????????

• 2.3.1 ??????
• FA?????????????acyl-CoA(??CoA),???????????
• ????acyl-CoA??????,????????

????????CoA??????????????
16
2.3.1 ??????(Activation of Fatty Acids)
AMP PPi
Cytosol
Fatty acid
CoA
Mitochondrial membrane space
Mitochondrial matrix
17
2.3.1 ??????

• ????????FA??
• ???acyl-CoA synthase,?????(thiokinase),??12???????
  FA(LehningerFatty acids are activated on the
  outer membrane of mitochondria)
• ???acyl-CoA synthase,??4-10????FA?
• ???ATP????,?Mg2
• R-COO- ATP HS-CoA ? R-CO-SCoA AMP PPi

???
?2Pi
18
2.3.1 ??????
??-CoA??????,?????????
19
2.3.2 ??CoA????? Transport of Acyl-CoA into
Mitochondrial Matrix

• FA??-oxidation???????????????
• ????FA??????????
• ??FA?????????????????,???(L-carnitine)???

????
20
?????????/??????????
???????II
FA-CoA
???????I
21
Transport of Acyl CoA into Mitochondrial Matrix
Outer membrane
Acyl CoA
Carnitine
Inner membrane
CoA
22
2.3.3 ?????-oxidation

• ???????????
• 1. ??
• 2. ??
• 3. ???
• 4. ??(?????)

????????????
23

• ????????

P234
Knoop? ???? b-??
24
2.3.3 ?????-oxidation
1. ??Acyl-CoA??????,????enoyl
CoA(??CoA),?????????3?acyl-CoA dHE,??FAD??????FAD
H2
??CoA???
?Gº -20.08 kJ/mol
25
2.3.3 ?????-oxidation
26
2.3.3 ?????-oxidation
2. ???2-enoyl-CoA???,??L-3-???CoA,??????,??????2-
?????CoA
??CoA???
a
b
?Gº -3.14 kJ/mol
L-3-???CoA
27
2.3.3 ?????-oxidation
3. ???L-3-???-CoA??,???-???-CoA,??????,??NAD???,
??L?????????NADH.
???CoA???
?-???-CoA
?Gº 15.69 kJ/mol
28
2.3.3 ?????-oxidation
4. ??(?????)????(thiolase, acetyltransferase)
(????????)???
???
?Gº -27. 82 kJ/mol
29
?????-oxidation??
?? ?? ??? ??
30
Three steps of b-oxidation and citric acid cycle
are very similar

• All involve the oxidation of a highly reduced
  carbon (from -CH2- to -CHO-)

Three similar reactions between
the b-oxidation and citric acid cycle
31
?????-oxidation ??

• 1.FA??????,??1 ATP????????,??????????
• 2.Acryl-CoA(??)??????????????,????????I?II
• 3.??FA? ?-?????????
• 4. ???????????2n,????n-1 ??-??

32
?????-oxidation ??

• 5. ?-oxidation??????????acetyl-CoA??TCA,????H2O
  ?CO2,????-oxidation????1 acetyl-CoA?1 FADH2?1
  NADHH?
• ??????,7?????8 acetyl CoA?7FADH2?7(NADHH
  )
• ?ATP??8 ? 10 7 ?(1.5 2.5) 2
  106(ATP)?
• 6. ?????

33
2.4 ???????????

• ??????????????,?????????-?????????,??????CoA?
• ??????????????????????????FA??????????????????(Val
  , ILe)???????,?????????????
• ?????????????????CoA???????
• ???????,????????????

34
2.4.1 ???????????-CoA??
3
TCA
35
2.4.1 ???????????-CoA??
36
2.4.1 ???????????-CoA??
37
2.4.2 ????ß-?????
38
2.4.3 ?????????CoA??
?????CoA
39
2.5 ?????????

• ????????????????????????
• 1)???????????????????(????????D-?-??),??-???????2-
  ???-CoA?????
• 2)????????????,????????2?,????3??4??

40
2.5 ?????????
?3????2?????1??FADH2?1.5ATP
???CoA???
41

• ???????????????

???CoA???
42
??????(???)???
2,4-????CoA???
?4-???-CoA
2,4-????-CoA
43
??????(???)???
???CoA???
2,4-????CoA???
???CoA???
44
2.6 ?????????????

• ????????????????,??????????????????,???????(Pero
  xisomes)???????????????????????
• ????????????????????????????????FADH2,???????O2?
  ?H2O2,?????????????

Electron micrograph of a peroxisome in a liver
cell.
45

• ??????????????-?????

46
2.7 FA?a-??

• Stumpf P K(1956)???????????,??????????????
  ???,????FA????,????????,?????D-?-??FA,?????????FA?
  

a-?????? ???????????? ?????????????
??
47

• FA??-???????

D-a-???

• ???????
• ???????
• D-a-????????

48
?????-??????????

• ????ß-??????,??????ß-??
• ??????-??,???????,???ß-??

CH3
CH3
CH3
CH3
COOH
H3C
???
CO2
?-??
CH3
CH3
CH3
CH3
H3C
COOH
????
?-??
49
?????-??????????
????
50
2.8 FA??-??

• Verkade(1932)??????????????????,?????????????????
  ?????,?????????????-???ß-???,??????????????????

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FA??-??

• ???????(???)
• ????????3??

???? ???? ????

• ?????????????????ß??
• ??????12??????????-??

52
FA??-??
???
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2.9 ????

• FA??-?????????CoA,???????TCA,??????????,
  ????????????????,??acetyl CoA???????????????-?????
  ??????,??????????(ketone body)?

• ????????,????????
• ??????????
• ??????????????,??????

54

• ??(Ketone Bodies)

????????????????????,??????????????????????
??
????
?-???
55

• 2.9.1 ????

?
?
???
?
HMG CoA??
?
?
?
??????CoA
56

• 2.9.1 ????

??????CoA
HMG CoA???
????
??
?-???
57
2.9.2 ???????

• Ketone bodies are converted to acetyl-CoA in
  extrahepatic (??)tissues
• ??????????,?-??????????????

????
2??CoA?TCA
58
?????????
???