13氨基酸代谢2013
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The essential amino acids cannot be made by humans and must be obtained in the diet.
人体不能合成的
2014-3-4
20
α-酮戊二酸
2014-3-4
21
3-磷酸甘油酸
2014-3-4
22
草酰乙酸
丙酮酸
2014-3-4 23
three sources:
1
1) glycolysis, 2) the citric acid cycle, and 3) the pentose phosphate pathway.
2
2014-3-4
18
6种代谢前体
Erythrose: 赤藓糖
2014-3-4
19
Most microorganisms can synthesize all 20 amino acids Humans can only synthesize 11 amino acids
19S regulatory subunit
2014-3-4
14
The 20S Proteasome 1. 700kD, 28 homologous subunits: 14 of type a and 14 of type b. 2. Subunits are arranged in 4 rings of 7 subunits each to form a sealed barrel.
2014-3-4 26
Ammonia Is Incorporated into Biomolecules through Glutamate and Glutamine
2014-3-4
27
2014-3-4
28
2014-3-4
29
2014-3-4
30
2、氨基酸的降解
2014-3-4
31
2、氨基酸的降解-1:引言
Nitrification (硝化) Denitrification (去硝化)
2014-3-4
25
Only certain prokaryotes can fix atmospheric nitrogen. These include the cyanobacteria (蓝藻类细菌) of soils and fresh and salt waters, other kinds of free-living soil bacteria such as Azotobacter (固氮菌) species, and the nitrogen-fixing bacteria that live as symbionts (共生体) in the root nodules of leguminous (豆类) plants.
http://www.genome.jp/kegg/pathway.html
2014-3-4
3
2014-3-4
4
1、氨基酸的来源: 蛋白质降解和生物合成
2、氨基酸的降解
3、氨基酸衍生物
2014-3-4
5
1、氨基酸的来源-1
小肠
Proteolysis of dietary proteins in the stomach and lumen of the small intestine releases free amino acids into the bloodstream.
The 19S regulatory subunits bind to polyubiquitin chains.
2014-3-4
17
1、氨基酸的来源-2: 生物合成
3
Overview of amino acid biosynthesis.
The carbon skeleton precursors derive from
氨基酸代谢
2014-3-4
1
引言
草酰乙酸 糖异生
2014-3-4
2
1.5 Amino Acid Metabolism Glutamate metabolism Alanine and aspartate metabolism Glycine, serine and threonine metabolism Methionine metabolism Cysteine metabolism Valine, leucine and isoleucine degradation Valine, leucine and isoleucine biosynthesis Lysine biosynthesis Lysine degradation Arginine and proline metabolism Histidine metabolism Tyrosine metabolism Phenylalanine metabolism Tryptophan metabolism Phenylalanine, tyrosine and tryptophan biosynthesis Urea cycle and metabolism of amino groups 1.6 Metabolism of Other Amino Acids beta-Alanine metabolism Taurine and hypotaurine metabolism Aminophosphonate metabolism Selenoamino acid metabolism Cyanoamino acid metabolism D-Glutamine and D-glutamate metabolism D-Arginine and D-ornithine metabolism D-Alanine metabolism Glutathione metabolism
Site:ψKXE, where ψ is an aliphatic (脂肪族) residue
2014-3-4 13
The 26S proteasome digests the ubiquitin tagged proteins
19S regulatory subunit
20S proteasome (catalytic activity)
2014-3-4 8
The Mark of Death
Ubiquitin (76 Res.)
C-terminal Gly attaches to the e-amino groups of several Lys on a protein destined for degradation. Additional ubiquitin molecules can be added to Lys48.
溶酶体
Proteolysis of proteins that move through the endocytic pathway takes place in the lysosomes of all cells.
蛋白酶体
Controlled proteolysis of ubiquitin-tagged intracellular proteins takes place in the proteasomes of all cells.
2014-3-4 9
Ubiquitin attached to the e-amino group of lysine residues on the target proteins
2014-3-4
10
Ubiquitin Conjugation
E1=Ubiquitin-Activating Enzyme E2=Ubiquitin-Conjugating Enzyme E3=Ubiquitin-Protein Ligase
2. Cyclin destructive boxes: specific amino acid sequences that mark cell-cycle proteins for destruction.
3. PEST sequences: proteins rich in proline, glutamic acid, serine and threonine.
磷酸烯醇式丙酮酸 赤藓糖-4-磷酸
Chorismate: 分支酸 Phosphoenolpyruvate: 磷酸烯醇丙酮酸 Erythrose 4-phosphate: 赤藓糖-4-磷酸
2014-3-4 24
1、氨基酸的来源-3:氮循环
The nitrogen cycle. The total amount of nitrogen fixed annually in the biosphere exceeds 1011 kg.
3. In well-nourished cells, lysosomal protein degradation is non-selective.
4. In starving cells, there is a selective pathway that preferentially degrades cytosolic proteins containing the pentapeptide KFERQ (Lys-Phe-Glu-Arg-Gln).
2014-3-4
11
A single ubiquitin molecule is a poor signal for degradation. Chains of 4 or more ubiquitin molecules are very strong signal for degradation.
2014-3-4
AMINO ACID POOL
6Βιβλιοθήκη Baidu
Lysosomal Degradation
1. Lysosomes degrade proteins taken up by endocytosis, or proteins that traffic within the endocytic pathway. 2. Lysosomes contain ~50 hydrolytic enzymes (proteases). Their pH optima is acidic, ~5.
2014-3-4
12
What determines whether a protein is ubiquitinated? The substrate specificity of each E3. 1. The N-terminal rule: the chemical nature of the aminoterminal amino acid.
7
7 7
7
2014-3-4 15
Proteolytic activity resides in the N-terminal threonine residues of the b subunits
7
7
7 7
2014-3-4
16
Access to the 20S proteasome is controlled by the 19S Caps
2014-3-4 7
Controlled Proteolysis
1. Ubiquitin tags proteins for destruction.
2.The proteasome digests the ubiquitin tagged proteins. 3.Protein degradation can be used to regulate biological function.
氨基酸发生降解的三种情形: 1. During the normal synthesis and degradation of cellular proteins, some amino acids that are released from protein breakdown and are not needed for new protein synthesis undergo oxidative degradation. 2. When a diet is rich in protein and the ingested amino acids exceed the body’s needs for protein synthesis, the surplus is catabolized; amino acids cannot be stored. 3. During starvation or in uncontrolled diabetes mellitus, when carbohydrates are either unavailable or not properly utilized, cellular proteins are used as fuel.
人体不能合成的
2014-3-4
20
α-酮戊二酸
2014-3-4
21
3-磷酸甘油酸
2014-3-4
22
草酰乙酸
丙酮酸
2014-3-4 23
three sources:
1
1) glycolysis, 2) the citric acid cycle, and 3) the pentose phosphate pathway.
2
2014-3-4
18
6种代谢前体
Erythrose: 赤藓糖
2014-3-4
19
Most microorganisms can synthesize all 20 amino acids Humans can only synthesize 11 amino acids
19S regulatory subunit
2014-3-4
14
The 20S Proteasome 1. 700kD, 28 homologous subunits: 14 of type a and 14 of type b. 2. Subunits are arranged in 4 rings of 7 subunits each to form a sealed barrel.
2014-3-4 26
Ammonia Is Incorporated into Biomolecules through Glutamate and Glutamine
2014-3-4
27
2014-3-4
28
2014-3-4
29
2014-3-4
30
2、氨基酸的降解
2014-3-4
31
2、氨基酸的降解-1:引言
Nitrification (硝化) Denitrification (去硝化)
2014-3-4
25
Only certain prokaryotes can fix atmospheric nitrogen. These include the cyanobacteria (蓝藻类细菌) of soils and fresh and salt waters, other kinds of free-living soil bacteria such as Azotobacter (固氮菌) species, and the nitrogen-fixing bacteria that live as symbionts (共生体) in the root nodules of leguminous (豆类) plants.
http://www.genome.jp/kegg/pathway.html
2014-3-4
3
2014-3-4
4
1、氨基酸的来源: 蛋白质降解和生物合成
2、氨基酸的降解
3、氨基酸衍生物
2014-3-4
5
1、氨基酸的来源-1
小肠
Proteolysis of dietary proteins in the stomach and lumen of the small intestine releases free amino acids into the bloodstream.
The 19S regulatory subunits bind to polyubiquitin chains.
2014-3-4
17
1、氨基酸的来源-2: 生物合成
3
Overview of amino acid biosynthesis.
The carbon skeleton precursors derive from
氨基酸代谢
2014-3-4
1
引言
草酰乙酸 糖异生
2014-3-4
2
1.5 Amino Acid Metabolism Glutamate metabolism Alanine and aspartate metabolism Glycine, serine and threonine metabolism Methionine metabolism Cysteine metabolism Valine, leucine and isoleucine degradation Valine, leucine and isoleucine biosynthesis Lysine biosynthesis Lysine degradation Arginine and proline metabolism Histidine metabolism Tyrosine metabolism Phenylalanine metabolism Tryptophan metabolism Phenylalanine, tyrosine and tryptophan biosynthesis Urea cycle and metabolism of amino groups 1.6 Metabolism of Other Amino Acids beta-Alanine metabolism Taurine and hypotaurine metabolism Aminophosphonate metabolism Selenoamino acid metabolism Cyanoamino acid metabolism D-Glutamine and D-glutamate metabolism D-Arginine and D-ornithine metabolism D-Alanine metabolism Glutathione metabolism
Site:ψKXE, where ψ is an aliphatic (脂肪族) residue
2014-3-4 13
The 26S proteasome digests the ubiquitin tagged proteins
19S regulatory subunit
20S proteasome (catalytic activity)
2014-3-4 8
The Mark of Death
Ubiquitin (76 Res.)
C-terminal Gly attaches to the e-amino groups of several Lys on a protein destined for degradation. Additional ubiquitin molecules can be added to Lys48.
溶酶体
Proteolysis of proteins that move through the endocytic pathway takes place in the lysosomes of all cells.
蛋白酶体
Controlled proteolysis of ubiquitin-tagged intracellular proteins takes place in the proteasomes of all cells.
2014-3-4 9
Ubiquitin attached to the e-amino group of lysine residues on the target proteins
2014-3-4
10
Ubiquitin Conjugation
E1=Ubiquitin-Activating Enzyme E2=Ubiquitin-Conjugating Enzyme E3=Ubiquitin-Protein Ligase
2. Cyclin destructive boxes: specific amino acid sequences that mark cell-cycle proteins for destruction.
3. PEST sequences: proteins rich in proline, glutamic acid, serine and threonine.
磷酸烯醇式丙酮酸 赤藓糖-4-磷酸
Chorismate: 分支酸 Phosphoenolpyruvate: 磷酸烯醇丙酮酸 Erythrose 4-phosphate: 赤藓糖-4-磷酸
2014-3-4 24
1、氨基酸的来源-3:氮循环
The nitrogen cycle. The total amount of nitrogen fixed annually in the biosphere exceeds 1011 kg.
3. In well-nourished cells, lysosomal protein degradation is non-selective.
4. In starving cells, there is a selective pathway that preferentially degrades cytosolic proteins containing the pentapeptide KFERQ (Lys-Phe-Glu-Arg-Gln).
2014-3-4
11
A single ubiquitin molecule is a poor signal for degradation. Chains of 4 or more ubiquitin molecules are very strong signal for degradation.
2014-3-4
AMINO ACID POOL
6Βιβλιοθήκη Baidu
Lysosomal Degradation
1. Lysosomes degrade proteins taken up by endocytosis, or proteins that traffic within the endocytic pathway. 2. Lysosomes contain ~50 hydrolytic enzymes (proteases). Their pH optima is acidic, ~5.
2014-3-4
12
What determines whether a protein is ubiquitinated? The substrate specificity of each E3. 1. The N-terminal rule: the chemical nature of the aminoterminal amino acid.
7
7 7
7
2014-3-4 15
Proteolytic activity resides in the N-terminal threonine residues of the b subunits
7
7
7 7
2014-3-4
16
Access to the 20S proteasome is controlled by the 19S Caps
2014-3-4 7
Controlled Proteolysis
1. Ubiquitin tags proteins for destruction.
2.The proteasome digests the ubiquitin tagged proteins. 3.Protein degradation can be used to regulate biological function.
氨基酸发生降解的三种情形: 1. During the normal synthesis and degradation of cellular proteins, some amino acids that are released from protein breakdown and are not needed for new protein synthesis undergo oxidative degradation. 2. When a diet is rich in protein and the ingested amino acids exceed the body’s needs for protein synthesis, the surplus is catabolized; amino acids cannot be stored. 3. During starvation or in uncontrolled diabetes mellitus, when carbohydrates are either unavailable or not properly utilized, cellular proteins are used as fuel.