Metabolism of Non-nutritive Material - PowerPoint PPT Presentation

1 / 106
About This Presentation
Title:

Metabolism of Non-nutritive Material

Description:

Metabolism of Bile Pigments and Jaundice ... (xenobiotics ... – PowerPoint PPT presentation

Number of Views:188
Avg rating:3.0/5.0
Slides: 107
Provided by: hp20
Category:

less

Transcript and Presenter's Notes

Title: Metabolism of Non-nutritive Material


1
?11?
???????
Metabolism of Non-nutritive Material
??????????? ??? yuanyuanch_at_njmu.edu.cn
2
? ? ? ?
??? ?????? ??? ????????? ???
???????? ??? ?????????
3
???
????????
Biotransformation in the Liver
4
??????????
(?)????????
????????????,???????,???????????????????????,?????
?????????
(?)????????
???????????????(????????)
???????????(???????
???)? ?????????????????????????
??????????
5
?????????????
??????????????????????
??????????????????
????????,???????????????????????????
6
????????
??????? ???????????????????????
(biotransformation)?
???????
??????????
?????
??????????
7
????????? ???????????,?????????????????????? ?
??????? ????????? (xenobiotics)????,????
(inactivate),??? (detoxicate)??????????????????,?
??????
? ????????????? (detoxification)
8
(?)?????????????
??????????????? ?????????
????????????????????
????????????,???????,??????????????,??????,??????
9
1.?????????????????
1) ????P450????
????P450????????????????
????????(?????) ??Cyt P450,NADPHH,
NADPH-???? P450??? ??????? RHO2NADPHH
? ROHNADPH2O
10
(No Transcript)
11
????
????????,??????????????,??????????,???????????
?????????? ??
??
?????
12
????? ??????
????
????
???? (???)
????-S- ???????
?????????
??? ??
??
???????
???????
??????????
13
2) ??-????
??-????????????????????????
  • ??-???? (flavin containing monooxygenase,
    FMO)???NADPH?FAD???,??????????????????????????????
    ?????
  • ?????????FMO???,???FMO3?FMO4?FMO5???,FMO3????????F
    MO????70?90?FMO1???????

14
??-????????
S S-O
FAD-OOH FMO NADP
O2
FAD-OH FMO NADP
FADH2 FMO NADP
H2O
FAD FMO NADP
FAD FMO NADPH
FAD FMO
NADP
NADPH
15
????
????
?????
N-???????
16
3) ?????
????? (monoamine oxidase, MAO)????????????
????????
?????
????
????
17
3,4,5-???????
????
3,4,5-???????
18
4) ?????????
??????????????????
???????
?????
???? (alcohol dehydrogenase, ADH)????????
CH3CH2OH NAD ??? CH3CHO NADH H
???? (aldehyde dehydrogenase, ALDH)???????
CH3CHO NAD H2O ??? CH3COOH NADH H
19
ADH??????????ALDH2????,??????????????,????????????
?????????????
???????????????????????????CYP2E1???????mRNA???,??
?????????? (microsomal ethanol oxidizing system,
MEOS)?CYP2E1??????????ADPH??,??????????,??????????
?????????????????
20
5) ?????????????
?????? (nitroreductase)???????(azoreductase)??I???
???????
????????
?????
??? ???? ??? ???
?????
??? ??????
N-???????
21
6) ??????????????
?? (esterases)???? (amidase)???????? (epoxide
hydrolase)???????????
??????????????
?????
?????????????????,???????????? ???????????? ??????
?????????????,????????????,???????????????????
22
????????
?????
???
???
?
???
???-7,8-??
DHEP-BP
23
2.??????????
?????????????????????????????????
??????????????????????????????????
24
1) ?????????
????????????????????
???????????????????
(UDPGA)
HOCH2 ? ?
COOH ? ?
2NADH 2H
O
O
2NAD
H ? ? ? OH
H ? ? ? OUDP
H ? ? ? OH
H ? ? ? OUDP
OH ? ? ? H
OH ? ? ? H
UDPG???
? ? OH
? ? OH
UDPG
UDPGA
25
??? ???????? (UDP-glucuronyl transferases, UGT)
????????
??
COOH ? C ? H
O
O
H ? C ? HO
C
UGT
UDPGA
OH ? C ? H
H ? C ? OH
OH
UDP
H
??
???????
26
2) ?????????????
????3?-????5?-???? (PAPS)
????????? (sulfotransferase, SULT)
???????
??
O
O
PAPS
PAP
HO3SO
HO
??
?????
27
3) ????????
????????GSH ???????S-??? (glutathione
S-transferase, GST) ???????
????B1-8,9- ????
???????? ????
28
4) ????????????????
???
???CoA
???
???CoA
??????
29
5) ??????????????????
????S?????? (SAM) ??????????
CONH2
CONH2
?????
S-??????
S-????????
N ? CH3
N
????
N-??????
30

6) ????????????????????
??????CoA ????????? ???????
CH3COCoA
HSCoA
???
????A
?????
??A
??
N-????
31
?.?????????
(?)????????????????? ?????
(?)????????????????? (???)
  • (?)?????????????????

32
?.???????????
(?)?????????????
??????????????????????????????,??????????????
33
2??????????
?????????
????????????????????CYP?UGT???,???????????????????

??????????
??????????????? (aryl hydrocarbons hydroxylase,
AHH)???
34
(?)?????????????????
?????????????????????????????????
?????????????????????????????????????????????????
??????
35
(?)????????????
1.??????????????? 2.????????????????? 3.?????????
?????? 4.????????????? 5.??????????????
6.???????????????
36
???
?????????
Metabolism of Bile and Bile Acids
37
???????????????
????
??? (hepatic bile)
???? (gallbladder bile)
?????
????????
????? ???? (bile salts)????????????????????????
38
??
(???)
????? ? ??? ? ?????
? ??????? ?
??? ? ???
(????)
?????? ????(????)?????(??????????????????)??????
39
??????????????
??? ????
?? 1.009?1.013 1.026?1.032
pH 7.1?8.5 5.5?7.7
? 96?97 80?86
???? 3?4 14?20
??? 0.2?0.9 0.5?1.1
??? 0.1?0.9 1?4
???? 0.5?2 1.5?10
??? 0.05?0.17 0.2?1.5
??? 0.1?0.5 1.8?4.7
??? 0.05?0.17 0.2?0.9
?? 0.05?0.08 0.2?0.5
40
????????
??????????????
???????? ?????????????/???
????
??????????????????? ???????????????????
????
41
?????
??
?????
42
?????
CONHCH2CH2SO3H
OH
12
?????
3
7
HO
OH
H
CONHCH2COOH
OH
12
?????
7
3
HO
OH
H
43
????? ???????????????????,????????????????????
????? ?????????????7?-???????????,???????????
44
?????
COOH
OH
12
??
3
7
HO
OH
H
COOH
OH
7?-????
12
????
3
7
HO
H
?????
45
?????
COOH
12
?????
7
3
HO
OH
H
7?-????
COOH
12
???
7
3
?????
HO
H
46
????????
??? (bile acids)??? ??????????????????,???????????
,?????,?????? (bile salts)? ?????????????????????
???????
47
??????????(?????)
?????????????
???
?????????
???
48
?????,??????????? ??????????????????? ? 101?
?????????????
49
??????????
?????????????????
????????(enterohepatic circulation of bile acid)
???????????,?????????????,????????????,???????????
??
???? (bile acid pool)
???????????,???????3?5g?
50
??????????????
?????????,??????????????????????????????????????,?
???????????,????????98?????????????,?????????????
???????Na????????? (apical sodium-dependent bile
salt transporter, ASBT)????????
????????????????????
51
? ? ? ? ? ? ? ? ? ?
52
????????????0.40.6g,???????????35g,?????????,???
??????612?????,???1232g????
????????????
1.??????????????????? 2.??????????,?????????
????? 3.????/????????,???????
53
????????????????
(?)??????????
(?)?????????????????? ???????????
54
???(gallstone)
????? (cholesterol stone)
??????????50 ????? (black pigment stone)
???????????1030 ????? (brown pigment
stone) ??????????
55
???
????????
Biosynthesis of Heme
56
??? (heme) ??????????? (hemoprotein)???,??????????
?????????????,????? (hemoglobin, Hb)?????
(myoglobin)????? (cytochrome)??????
(catalase)??????(peroxidase)??
57
????????
??
??????????,?????Fe2????? ??????????,
???????????? (porphyrinogens),??????
(porphyrin)????? ?????????,????,????,?????????????
?????? ?????????,??????????????? ????????,????????
?????????,??????,??????????? (porphyria)?
?
?
?
?
58
(No Transcript)
59
??????????
????? ??????????????????
??????????????
???????? ???????????? ?????????
????? ???????CoA?Fe2
60
????
1.?-??-?-??? (ALA)???
??????????????-??-?-??? (?- aminolevulinic acid,
ALA)?ALA?? (ALA synthase)??,???????????
???????
COOH ? H2C ? CH2 ?
CO ? CH2NH2
COOH ? H2C ? CH2 ?
CSCoA ? O
HSCoA CO2
CH2NH2 ? COOH

ALA?? (?????)
?????A
???
ALA
61
2.???????
ALA???????????ALA????????????
COOH ? CH2 ?
CH2 ? OC ? HCH
? HNH
O
OH
COOH ? H2C ? CH2 ?
CO ? CH2 ? NH2
HO
O
N H
H2N
????(PBG)
62
3.????????????
????????????????????
????????UPG I (???????)
4????
?????
????III???
????III???
?????
?????
63
4.??????
????????III??????,?????
???????
????? ?????
?????
?????
????? ???
?????
????
???
64
???
??
???
????
2
ALA
ALA
????
4
???
??? ?????A
3NH3
?????
???IX
NH3
2CO2 4H
CO2
????III
????III
????IX
65
????????
? ?????????????,?????? ???? ?
??????????CoA????Fe2?
????? ? ???????????????????,
????????
66
???????
?????????????????? ???????????????,??????????
67
????????????
1.ALA??
????????????,??????????, ????????,???????????, ???
??????, ?????????????
68
2.?????ALA?????????
??????ALA???,???????????,????????????????,?????
???????(????)????????????(?????)?
3.??????? (erythropoietin, EPO)
???????????????????,????????,????? ??????,????????
??????? ?Hb???,??????????????
69
???
?????????
Metabolism of Bile Pigments and Jaundice
70
??????????????????
??? (bile pigment)??????????????????,?????????????
?????
71
(?)?????????????
??? (bilirubin)?? ??????????????????????????????
??????
?80????????????????
72
(?)????????
?????????????????????
???????????-????????????????
??
????
??? ???
???
???
?????? ????,?????????
73
? ? ? ? ? ? ? ?
CO??????,??????????????
74
(?)??????????????????
????????????????????????,??????????????????,??????
??????,?????????????,?????????????,???????? ??????
lt5?-???(?-????????),???????????????
75
?????
????
O
H
N
O
H
C
O
98
H
N
N
H
O
H
N
C
O
H
O
???????????
???????
76
(?)?????????????
1.???????????????????
CO????????????????????,??cGMP????
2.??????????
???????????????????,???????????????
77
(No Transcript)
78
????????????
???? ???-??????
???? ?????????????,???????????????????
????? ????,???,????
79
????????????????????, ????????,????????????
????????????????????? ??,???????????????????
??????/????/????? ????????,????????????????,??????
???
80
?????????????????????????
  • (?)????????????????

???????????????????????????,???????? ?????????????
???? ?????????-??????????????????????
81
Y???Z???????????
??????????????Y???Z?????,???Y????? Y??,?????
(ligandin)???????????????
82
(?)???????????
?????????? ??????(???????UDP????
?,UDPGA) ?????????? ??????????????,????
???????????????, ????????
83
??????????
????????? UDPGA
??? UDPGA
UDP-????????
UDP-????????
????????? UDP
????????? UDP
84
????????????
H
H
H
H
H N
H N
H N
H N
O
O
? CH2 ? CH2 ? CO ? O ? ? ? ? H
? CH2 ? CH2 ? CO ? O ? ? ? ? H
HOOC ? H
COOH ? H
O
O
H ? ? OH
H ? ? OH
OH ? ? H
H ? ? HO
OH ? ? H
H ? ? HO
85
???
2UDP-????
UDP-????????
2UDP
????????
86
????????????
? ? ????? ?????
? ? ????? ???? ????? ????
??????? ??? ??
??????? ?????? ??????
????? ? ?
??? ? ?
??????? ? ?
?????? ?? ?
???????? ???? ? ?
87
????????
??
?????
????
?????
??
???????????????,??????????,???????????????????,???
?????????????,?????????
88
(?)????????????????
???????????????????????
???????2 (MRP2)?????????????????????
89
??????????????????
??
?????
?????
????
? ?
???
??
???
??
???d-????,????,????
??d-???,i-???,???
90
(?)???????????
8 H
???
8 H
d-????
- 2 H
d-???
????(i-????)
4 H
- 2 H
??? (i-???)
?????? ?????
????(l-????)
- 2 H
P-CH2-CH2-COOH
??? (l-???)
91
(?)???????? (1020)
????????????????????,??????,?????????????,????????
?? (bilinogen enterohepatic circulation)?
92
??-????
??
???
? ? ? ? ? ? ? ? ? ?
???? ??? ??? ???
???
??
???
???-??? ???
Y?? Z??
???-Y?? ???-Z??
2O2 Fe3 H2O CO
NADPHH NADP
UDPGA UDP
???
???????
???? (MRP2)
NADPHH NADP
???
? ?
???(??)
???
?
??
???
???????
O2
O2
???
??
??
???
????
?
??
93
????????????????
???????????????
??????????????
94
????????????????
???????????3.4?17.1?mol/L (0.2?1mg/dl),??????????
????????????????,??????????????
??????????17.1?mol/L (1mg/dl)?????????
?????????,???????????????????,????????(jaundice)?
95
??
?????
??(????????????) 1.????? (hemolytic
jaundice) 2.????? (obstructive
jaundice) 3.?????? (hepatocellular jaundice)
96
??
1.????? (hemolytic jaundice)
??????????-?????????
?,???????,???????? ???????,?????????
???????
???????????????????? ?????
97
??
98
??
????? ?????
?????? ?
?????? ?
????? -
???? ????
???? -
??? ?
??? ?
??? ?
??? ?
99
??
2.?????? (hepatocellular jaundice)
???????????,???????? ?????????????
????????,??????????
100
??
101
??
?????? ??????
?????? ?
?????? ?
????? ?
???? ????
????
??? ???
??? ???
??? ????
??? ????
102
??
3.????? (obstructive jaundice)
?????????????,??????,
???????????????, ??????????,
????????????
????????(???)??????? ????????
103
??
104
??
????? ?????
?????? ?
?????? -
????? ??
???? ????
????
??? ?
??? ?
??? ??-
??? ?
105
??
????????????
?? ?? ????? ?????? ?????
?????
?? lt1mg/dl gt1mg/dl gt1mg/dl gt1mg/dl
????? ?? ? ??
????? 00.8 mg/dl ?? ?
???
???? - -
???? 04 mg/24 h ? ??? ?
??? ?? ? ??? ?
???? ?? ? ????? ????? ?????
?????, ??????
106
? ? ??
???????????????????????? ???????????????????? ????
???????????????? ??????? ??????????????? ?????????
,? ??????????? ?????????? ??????
Write a Comment
User Comments (0)
About PowerShow.com