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1
Metabolism of protein &
amino acids
2
A. The physiological &
nutritious function of
proteins
3
B. nitrogen balance &
protein requirement
4
1. nitrogen balance
a. concept
b. experiment
5
c. 3 conditions
nitrogen equilibrium
negative nitrogen balance
positive nitrogen balance
6
2. minimal requirements of
protein
3.essential amino acids and
their biological value
7
8
an indicator to valuate the
nutritional value of the proteins
biological value
100 的吸收量的保留值
蛋白质的生理价值=N
N
9
4. Complementary function
of proteins
B. Digestion ,absorption,&
putrefaction of proteins
10
diet protein amino acids digestion
Proteolytic
enzyme
a. digestion
11
b. absorption
site
mechanism
characteristics
12
14
c. putrefaction
concept
15
未被消化的蛋白质 , 未被吸收的氨基酸,肽
large intestine
bacterias
Decarboxylation
deamination
有毒; amine ,H2S indole
hydroxybenzene 、 ammonia ( NH3) 、
other :CO2,CH4
Nutriment
Fatty acid 、 vit
Absorption in intestine excrete
blood
liver
16
• decarboxylation
• reductive & deamination
17
18
19
• the sources of ammonia in the
intestine
20
blood infiltrate intestine
kidney
excrete ( 20g )
NH2-CO-NH2
liver
NH3
(25%)7g
NH2-CO-
NH2
urease (bacterias)
2NH3+CO2 ( 4g
)
importance sources of blood ammonia-----
- absorpted from intestine
21
C. general metabolism
of amino acids
1. Sketch plan
23
Dietary protein
Tissue protein
amination of α—keto acids
degradation
Synthesis
85%
Non essential A.A
Digest,absorption
deamination
amines
NH3 α—keto acids
oxidation Glucose, fats
N.EAA
decarboxylation
Amino acid
metabolic
pool
urea
other substances
24
2. deamination of amino acids
a.oxidative deamination
1) reaction
25
26
2 ) enzymes
• L-amino acid oxidase
• D-amino acid oxidase
• L-glutamate dehydrogenase
27
28
• characteristics
b . transamination
1) reaction
29
30
2) important transamination
system.
31
glutamic pyruvic transamination system ( glutamic pyruvic transaminase,GPT )( alanine transaminase,ALT )
glutamic oxaloacetic transamination systen: ( glutamic oxaloacetic transaminase, ,GOT )( aspartate transaminase,AST)
32
NH2 O O NH2
Glu 丙酮酸 α— 酮戊二酸 Ala
NH2 CO-COOH O CH-COOH
NH2
Glu 草酰乙酸 α— 酮戊二酸 ASP
COOH-(CH2)2-CH-COOH + CH3-C-COOH COOH-(CH2)2-C-COOH+CH3-CH-COOH
COOH-(CH2)2-CH-COOH + CH2COOH COOH-(CH2)2-C-COOH+CH2-COOH
ALT
AST
33
2) enzyme & coenzyme
35
36
3) biological significance &
characteristics
37
c. combined deamination
1) reaction
38
39
40
41
2) biological significance &
characteristics
42
d. purine nucleotide cycle
1) site
2) reaction
43
44
3) characteristics
45
d. nonoxidative deamination
• dehydrate deamination
• direct deamination
46
47
3. Metabolism of ammonia
a. the sources of ammonia
48
the detail about the sources
of ammonia
49
protein
putrefaction
Urea cycle in liver&intestine
Absorption in intestine
( oxidation of amine )
deamination
Blood ammonia
Ala
(liver)
Gln
sources of blood ammonia
50
* protein putrefaction
51
blood infiltrate intestine
kidney
excrete ( 20g )
NH2-CO-NH2
liver
NH3
(25%)7g
NH2-CO-
NH2
urease
2NH3+CO2 ( 4g
)
importance sources of blood ammonia-----
- absorpted from intestine
NH4 excrete from feces
*Urea cycle in liver & intestine
52
According to the pH in intestine
pH NH3 + H+ NH 4+ excrete
pH absorpted to venous blood
53
protein
putrefaction
Urea cycle in liver&intestine
Absorption in intestine
( oxidation of amine )
deamination
Blood ammonia
Ala
(liver)
Gln
sources of blood ammonia
54
* hydrolysis of Gln
55
• the fates of ammonia
produced in renal cell
excrete to the kidney
reabsorption to vein blood
56
According to renal tube pH
pH NH3 + H+ NH4+ excrete
pH absorpted to venous blood
57
Putrefaction in
small intestine
Intestine-liver
cycle of urea
Absorption
In small intestine
( oxidation of amines )
deamination of A.A
Ammonia
in blood
Ala in liver
GLn
58
*Ala
59
b. The transportation of
ammonia
• synthesis & utilize of Gln
materials : Glu , NH3
60
energy: ATP
enzyme: Gln synthetase
reaction:
61
62
product: Gln
Biological significances
,
63
• glucose-alanine cycle
process
64
65
biological significance
66
Putrefaction in
small intestine
Intestine-liver
cycle of urea
Absorption
In small intestine
( oxidation of amines )
deamination of A.A
Ammonia
in blood
Ala in liver
GLn
67
c. the fates of ammonia
68
Synthesis of non essential A.A or other nitrogen compounds
muscle or other tissues
Gln
muscle
ureaNH3
Ala
liver
69
1) synthesis of urea---main
outlet of ammonia
a. site
b. process (ornithine cycle )
70
* 肝脏是合成尿素最主要的器官
血 尿
切肝犬 尿素 氨 尿素
用氨基酸饲养切肝犬 尿素 氨基酸
尿素 切肾犬
急性黄色肝委缩
氨基酸
尿素 ( - ) 氨 尿素 ( - )
72
73
This cycle included:
1 overall reaction
2 materials
3 stages
4 steps
5 enzymes
74
a. materials
15NH4Cl
NaH14CO3
Feed
dogs
14C=O
15NH2
15NH2
75
b. 3 stages
ornithine+ NH3+ CO2 citrulline+H20
citrulline+ NH3 arginine+ H20
arginine+ H20 urea+ ornithine
2ATP
1ATP
77
NH2 NH2
(CH2)3 C=O
+ NH3+ CO2 NH + H2O
CH NH2
(CH2)3
CH NH2 ornithine
citrulline
COOH
COOH
2ATP
78
NH2 NH2
C=O
NH + NH3 NH + H2O
(CH2)3
CH-NH2
COOH Citrullinc Arginine
C=NH
(CH2)3
CH-NH2
COOH
1ATP
79
NH2
C=NH
NH +H2O
(CH2)3
CH-NH2
COOH
Arginine
NH2 + (CH2)3
C=O CH-NH2
Orrnithine
COOH
NH2
NH2
urea
80
NH3 ( 2 molecules )
CO2 ( 1 molecules ) materials
urea
H2O
products
Ornithine
Citrulline
arginine
intermediates
81
c. Intermediate process
( 4 steps, 5 enzymes )
1) synthesis of carbomoyl
phosphate (mitochondria)
82
83
NH3+CO2+H2O+2ATP
NH2-CO-O~PO32-+Pi
carbomoyl phosphate synthetase 1
84
• enzyme
carbamoyl phosphate synthetase 1 carbamoyl phosphate synthetase II
85
carbomoyl phosphate carbomoyl phosphate
synthetase 1 synthetase II
Site mitochondria cytosol
source of NH3 Gln
nitrogenActivator AGA -
(N-Acetylglutamic acid )FinalProduct urea pyrimidine
86
2) synthesis of citrulline
(mitochondria)
• enzyme
ornithine transcarbomoylase
87
88
3) synthesis of arginine
(cytosol)
• enzyme
Argininosuccinate synthetase,ASAS Argininosuccinate lyase ASAL
ASAS------ Key enzyme
89
90
4) cleavage of arginine
(cytosol)
91
93
94
d. Overall reaction
3ATP+CO2+2NH3 +H2O NH2-CO-NH2
f. summarize
95
c. Regulation of urea synthesis
food
enzymes (AGA)
intermediates
96
97
d. biological significant of
urea synthesis
98
Synthesis of non essential A.A or other nitrogen compounds
muscle or other tissues
Gln
muscle
ureaNH3
Ala
liver
99
4. Metabolism of -keto acids
Amino
acid
NH3
Ala
Gln
ureaAmination of a-keto acids
Amination or transamination
To form non E.A.A.
Conversion of fat,glucose
Via TCA cycle oxidized to CO2 & H2O
-keto acids
100
1) Amination or transamination
To form non E.A.A.
α- ketoglutarate Glu
Pyruvate Ala oxaloacetate Asp
101
Glu
α- ketoglutarate
oxaloacetate
Asp
TCA cycle
102
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
103
TCA cycle is the hinge
of metabolism of lipids ,
carbohydrates, proteins
104
*
*
*
*
*
*
*
*
105
3) oxidation & provide energy
3. decarboxylation
106
Amino acids - CO
2
α-keto acids
amines
Non E.A.A
Conversion to lipids, carbohydrates
TCA cycle- NH 3
107
Enzymes & coenzyme
some important amines
108
a.γ-amino butyric acid
(GABA )
formation
109
enzyme
function
metabolic fate
110
b. 5-hydroxy tryptamine or
( serotonin )formation
111
function
c. taurine
formation
112
function
d. histamine
formation
113
e. polyamines
formation
114
115
D. metabolism of individual
amino acids
1. one carbon units
116
Concept
kinds
117
118
the carrier of one carbon unites
--------------THF
120
the sources & conversion
NH2-CH——COOH +FH4 NH2-CH— ( CH2 ) 2+N5-CH3-FH4 转甲基酶
( CH2 )
2
S
CH3
SH COOH
121
122
123
function
one carbon units &
medicine
124
2. metabolism of sulfur-
containing amono acids
types
125
Met
cysteine,Cys cystine
126
a.Met and Transfer of
methyl group
S-adenosylmethionine
(SAM)
127
Structure of SAM
128
Function of SAM
methionine cycle
B12 & methionine
cycle
129
B12
130
3. metabolism of cystein &
cystine
structure & characteristics
131
Formation of GSH
132
Catabolism of Cys
Cys
-NH2
pyruvate NH3 H2S
H2S SO42- 2ATP
Excrete in uria PAPS ( active sulfate )
133
The structure & function
of PAPS
( 3’-phosphoadenosine-
5’phosphosulfate
134
135
4. metabolism of side
chain amino acids
Type: Val,Ile,Leu
Catabolic process
(extrahepatic tissue )
136
Val 、 Ile 、 Leu
α-ketoacids
α-ketoglutarate Glu NH3
Gln
Ala pyruvate
liver
urea glyconeogenesis
Blood
137
5. metabolism of
aromatic amino acids
Type: Phe,Tyr,Trp
Catabolic process
(hepatic tissue)
138
Catabolic process of Phe
139
140
Albinism,
Phenylketonuria, (PKU)
Alkaptonuria
BCAA/AAA 3:1