Download NH 2

Metabolism of protein &
amino acids
1
A. The physiological &
nutritious function of
proteins
2
B. nitrogen balance &
protein requirement
3
1. nitrogen balance
a. concept
b. experiment
4
c. 3 conditions
nitrogen equilibrium
negative nitrogen balance
positive nitrogen balance
5
2. minimal requirements of
protein
3.essential amino acids and
their biological value
6
7
an indicator to valuate the
nutritional value of the proteins
biological value
N的保留值
蛋白质的生理价值＝
 100
N的吸收量
8
4. Complementary function
of proteins
B. Digestion ,absorption,&
putrefaction of proteins
9
a. digestion
digestion
diet protein
amino acids
Proteolytic
enzyme
10
b. absorption
site
mechanism
characteristics
11
12
c. putrefaction
concept
14
未被消化的蛋白质,未被
吸收的氨基酸，肽
Decarboxylation
large
intestine
有毒； amine ,H2S
indole
deamination
other：
CO2,CH4
hydroxybenzene、
ammonia（NH3)、
Absorption in intestine
bacterias
Nutriment
Fatty acid、vit
excrete
blood
15
liver
• decarboxylation
• reductive & deamination
16
17
18
• the sources of ammonia in the
intestine
19
blood
kidney
infiltrate
NH2-CO-NH2
(25%)7g
liver
excrete（20g） NH3
intestine
NH2-CONH2
urease
(bacterias)
2NH3+CO2（4g）
importance sources of blood ammonia----- absorpted from intestine
20
C. general metabolism
of amino acids
1. Sketch plan
21
decarboxylation
amines
Dietary
protein
Amino acid
degradation
Tissue
protein
metabolic
pool
Synthesis
85%
amination of
α—keto acids
deamination
Non essential
A.A
urea
NH3
α—keto acids
oxidation
Glucose, fats
23
other substances
N.EAA
2. deamination of amino acids
a.oxidative deamination
1) reaction
24
25
2 ) enzymes
• L-amino acid oxidase
• D-amino acid oxidase
• L-glutamate dehydrogenase
26
27
• characteristics
b . transamination
1) reaction
28
29
2) important transamination
system.
30
glutamic pyruvic transamination system
（glutamic pyruvic transaminase,GPT）
（alanine transaminase,ALT）
glutamic oxaloacetic transamination systen:
（glutamic oxaloacetic transaminase, ,GOT）
（aspartate transaminase,AST)
31
ALT
COOH-(CH2)2-CH-COOH + CH3-C-COOH
NH2
COOH-(CH2)2-C-COOH+CH3-CH-COOH
O
丙酮酸
Glu
O
NH2
α—酮戊二酸
Ala
AST
COOH-(CH2)2-CH-COOH + CH2COOH
NH2
CO-COOH
COOH-(CH2)2-C-COOH+CH2-COOH
O
CH-COOH
NH2
Glu
草酰乙酸
α—酮戊二酸
ASP
32
2) enzyme & coenzyme
33
35
3) biological significance &
characteristics
36
c. combined deamination
1) reaction
37
38
39
40
2) biological significance &
characteristics
41
d. purine nucleotide cycle
1) site
2) reaction
42
43
3)
characteristics
44
d. nonoxidative
deamination
• dehydrate deamination
• direct
deamination
45
46
3. Metabolism of ammonia
a. the sources of ammonia
47
the detail about the sources
of ammonia
48
sources of blood ammonia
（oxidation of amine )
deamination
protein
putrefaction
Urea cycle in
liver&intestine
Absorption
in intestine
Gln
Blood
ammonia
Ala
(liver)
49
* protein putrefaction
50
*Urea cycle in liver & intestine
blood
kidney
infiltrate
NH2-CO-NH2
(25%)7g
liver
intestine
NH2-CONH2
urease
2NH3+CO2（4g）
excrete（20g） NH3
excrete from feces
importance sources of blood ammonia----NH4
- absorpted from intestine
51
According to the pH in intestine
pH NH3 + H+
NH 4+ excrete
pH
absorpted to venous blood
52
sources of blood ammonia
（oxidation of amine )
deamination
protein
putrefaction
Urea cycle in
liver&intestine
Absorption
in intestine
Gln
Blood
ammonia
Ala
(liver)
53
* hydrolysis of Gln
54
•
the fates of ammonia
produced in renal cell
excrete to the kidney
reabsorption to vein blood
55
According to renal tube pH
pH
pH
NH3 + H+
NH4+ excrete
absorpted to venous blood
56
（oxidation of amines）
Putrefaction in
deamination of A.A
small intestine
Absorption
In small
intestine
Ammonia
in blood
GLn
Intestine-liver
cycle of urea
Ala in liver
57
*Ala
58
b. The transportation of
ammonia
• synthesis & utilize of Gln
materials : Glu , NH3
59
energy: ATP
enzyme: Gln synthetase
reaction:
60
61
product: ,Gln
Biological significances
62
• glucose-alanine cycle
process
63
64
biological significance
65
（oxidation of amines）
Putrefaction in
deamination of A.A
small intestine
Absorption
In small
intestine
Ammonia
in blood
GLn
Intestine-liver
cycle of urea
Ala in liver
66
c. the fates of ammonia
67
urea
Synthesis of non
essential A.A or
other nitrogen
compounds
muscle or
other tissues
NH3
Gln
liver
muscle
Ala
68
1) synthesis of urea---main
outlet of ammonia
a. site
b. process (ornithine cycle )
69
血
切肝犬
用氨基酸饲养切肝犬
尿素
尿素
尿
氨
尿素
氨基酸
切肾犬
尿素
急性黄色肝委缩
尿素 （-）
氨
氨基酸
尿素 （-）
*肝脏是合成尿素最主要的器官
70
72
This cycle included:
1 overall reaction
2 materials
3 stages
4 steps
5 enzymes
73
a. materials
15NH
4Cl
Feed
dogs
15NH
2
15NH
2
14C=O
NaH14CO3
74
b. 3 stages
2ATP
ornithine+ NH3+ CO2
citrulline+H20
1ATP
citrulline+ NH3
arginine+ H20
arginine+ H20
urea+ ornithine
75
NH2
NH2
C=O
(CH2)3
2ATP
+ NH3+ CO2
CH
NH + H2O
NH2
(CH2)3
COOH
CH
NH2
ornithine
COOH
citrulline
77
NH2
NH2
C=O
C=NH
1ATP
NH
+ NH3
NH
+ H2O
(CH2)3
(CH2)3
CH-NH2
CH-NH2
COOH
Citrullinc
COOH
Arginine
78
NH2
C=NH
NH2
NH +H2O
NH2 +
(CH2)3
(CH2)3
C=O
CH-NH2
CH-NH2
NH2
COOH
COOH
Arginine
urea
Orrnithine
79
materials
NH3 （2 molecules）
CO2 （1 molecules ）
urea
products
H2O
Ornithine
intermediates
Citrulline
arginine
80
c. Intermediate process
( 4 steps, 5 enzymes )
1) synthesis of carbomoyl
phosphate (mitochondria)
81
82
NH3+CO2+H2O+2ATP
carbomoyl phosphate
synthetase 1
NH2-CO-O~PO32-+Pi
83
• enzyme
carbamoyl phosphate synthetase 1
carbamoyl phosphate synthetase II
84
carbomoyl phosphate
synthetase
carbomoyl phosphate
1
Site
mitochondria
source of
NH3
nitrogen
Activator
AGA
(N-Acetylglutamic acid )
Final
Product
urea
synthetase II
cytosol
Gln
-
pyrimidine
85
2)
synthesis of citrulline
(mitochondria)
• enzyme
ornithine transcarbomoylase
86
87
3) synthesis of arginine
(cytosol)
• enzyme
Argininosuccinate synthetase,ASAS
Argininosuccinate lyase
ASAL
ASAS------ Key enzyme
88
89
4) cleavage of arginine
(cytosol)
90
91
93
d. Overall reaction
3ATP+CO2+2NH3 +H2O
NH2-CO-NH2
f. summarize
94
c. Regulation of urea synthesis
food
enzymes (AGA)
intermediates
95
96
d. biological significant of
urea synthesis
97
urea
Synthesis of non
essential A.A or
other nitrogen
compounds
muscle or
other tissues
NH3
Gln
liver
muscle
Ala
98
4. Metabolism of -keto acids
Ala
Gln
NH3
urea
Amination of aketo acids
Amino
acid
-keto
acids
Conversion of fat,glucose
Amination or transamination
To form non E.A.A.
Via TCA cycle oxidized to CO
&
99 2
H2 O
1) Amination or transamination
To form non E.A.A.
α- ketoglutarate
Pyruvate
oxaloacetate
Glu
Ala
Asp
100
Glu
α- ketoglutarate
TCA cycle
oxaloacetate
Asp
101
2) Conversion to lipids or
carbohydrates
glycogenic amino acid, such as :
Ala、Arg、Asp etc（13 ）
ketogenic amino acid such as:
leu lys (2)
glycogenic & ketogenic amino
acids such as : Ilu,Phe,Trp,Tye
102
TCA cycle is the hinge
of metabolism of lipids ,
carbohydrates,
proteins
103
*
*
*
*
*
*
*
*
104
3) oxidation & provide energy
3. decarboxylation
105
Non E.A.A
Amino
acids
α-keto
acids
amines
TCA cycle
Conversion to lipids,
carbohydrates
106
Enzymes & coenzyme
some important amines
107
a.γ-amino butyric acid
(GABA）
formation
108
enzyme
function
metabolic fate
109
b. 5-hydroxy tryptamine or
( serotonin）
formation
110
function
c. taurine
formation
111
d. histamine
formation
function
112
e. polyamines
formation
113
114
D. metabolism of individual
amino acids
1. one carbon units
115
Concept
kinds
116
117
the carrier of one carbon unites
--------------THF
118
the sources & conversion
转甲基酶
NH2-CH——COOH +FH4
（CH2）2
NH2-CH—（CH2）2+N5-CH3-FH4
COOH
SH
S
CH3
120
121
122
function
one carbon units &
medicine
123
2. metabolism of sulfurcontaining amono acids
types
124
Met
cystine
cysteine,Cys
125
a.Met and Transfer of
methyl group
S-adenosylmethionine
(SAM)
126
Structure of SAM
127
Function of SAM
methionine cycle
B12 & methionine
cycle
128
B12
129
3. metabolism of cystein &
cystine
structure & characteristics
130
Formation of GSH
131
Catabolism of Cys
Cys
-NH2
pyruvate
NH3
H2S
Excrete in uria
H2S
SO42-
PAPS（active sulfate）
132
The structure & function
of
PAPS
( 3’-phosphoadenosine5’phosphosulfate
133
134
4. metabolism of side
chain amino acids
Type: Val,Ile,Leu
Catabolic process
(extrahepatic tissue )
135
α-ketoacids
Val、Ile、Leu
α-ketoglutarate
Ala
Glu
NH3
Gln
pyruvate
Blood
liver
glyconeogenesis
urea
136
5. metabolism of
aromatic amino acids
Type: Phe,Tyr,Trp
Catabolic process
(hepatic tissue)
137
Catabolic process of Phe
138
139
Albinism,
Phenylketonuria, (PKU)
Alkaptonuria
BCAA/AAA 3:1
140