1. Protein Degradation and Amino Acids Metablism
蛋白质的分解代谢
Protein Degradation and Amino Acids Metablism

2. Contents Protein degradation Amino Acid Degradation
Biosynthesis of amino acids

3. I. Protein Degradation

4. Biological Functions of Proteins
Enzymes
Transport proteins
Nutrient and storage proteins
Contractile or motile proteins
Structural proteins
Defense proteins
Regulatory proteins
Other proteins

5. Nitrogen balance Zero or total nitrogen balance:
the intake = the excretion
(adult)
Positive nitrogen balance:
the intake > the excretion
（during pregnancy, infancy, childhood and recovery from severe illness or surgery ）
Negative nitrogen balance:
the intake < the excretion
（following severe trauma, surgery or infections. Prolonged periods of negative balance are dangerous and fatal. ）

6. Classification of amino acids
non-essential amino acids
- can be synthesized by an organism
- usually are prepared from precursors in 1-2 steps
Essential amino acids ***
- can not be made endogenously
- must be supplied in diet

7. Nonessential Essential Alanine Arginine* Asparagine Histidine *
Aspartate
Valine
Cysteine
Lysine
Glutamate
Isoleucine
Glutamine
Leucine
Glycine
Phenylalanine
Proline
Methionine
Serine
Threonine
Tyrosine
Tyrptophan
*The amino acids Arg, His are considered “conditionally essential” for reasons not directly related to lack of synthesis and  they are essential  for growth only

8. Degradation of dietary proteins

9. Degradation of proteins
Degraded by ubiquitin(泛素) label
2. Degraded by the protease and the peptidase in the Lysosome(溶酶体）

10. 1. Degraded by ubiquitin(泛素) label
Ubiquitin, a extremely well conserved 76-residue protein, Ubiquitin binds lysine side chain
Degrade abnormal protein of her own
Targets for hydrolysis by proteosomes in cytosol and nucleus
ATP required

11. 2. Degraded by the protease and the peptidase in the Lysosome(溶酶体）
non- ATP required
the hydrolysis-selective are bad
Degrade adventive protein

12. The ubiquitin degradation pathway E2：carrier protein E3：ligase
ATP AMP+PPi
E2-SH E3
E1-S-
E2-S-
（ubiquitin）
E1-SH
E2-SH
E1-SH
E1：activiting enzyme
E2：carrier protein E3：ligase
ubiquitinational protein
ATP
19S regulate substrate
ATP
20S Proteasome
26S Proteasome

13. II. Amino acids Degradation

14. The catabolism of amino acids

15. I. Deamination A. Transamination B. Oxidative deamination
C. Combined Deamination

16. A. Transamination Transamination by Aminotransferase (transaminase)
always involve PLP coenzyme (pyridoxal phosphate)
reaction goes via a Schiff’s base intermediate
all transaminase reactions are reversible

17. Transamination
aminotransferases

18. B. Oxidative Deamination
L-glutamate dehydrogenase (in mitochondria)

19. C. Combined Deamination
1. Transamination + Oxidative Deamination ?

20. 2. Transamination + purine nucleotide cycle
NH3 AA
Asp
-Keto
glutarate
IMP
H2O
aminotransferases
AST
2. Transamination + purine nucleotide cycle
AMP
-Keto
acid
Oxaloacetate
fumarate
malate

21. II. Decarboxylation
The decarboxylation of AAs produce some neurotransmitters’ precursors – bioactive amines

22. -aminobutyric acid (GABA)
Glutamine can be decarboxylated in a similar PLP-dependent fashion, outputting -aminobutyric acid (neurotransmitter, GABA)
L-Glu decarboxylase
– CO2
GABA
L-Glu

23. Histidine decarboxylase
L-Histidine
– CO2
Histidine decarboxylase
Histamine
强烈的血管舒张剂。增加血管的通透性，降低血压，甚至死亡。
Histamine

24. III. The metabolism of α-ketoacid
Biosynthesis of nonessential amino acids
TCA cycle member + amino acid α-keto acid + nonessential amino acid
A source of energy (10%) ( CO2+H2O )
Glucogenesis and ketogenesis

25. Fate of the C-Skeleton of Amino Acids

26. Ⅳ . ammonia metabolism
Fix ammonia onto glutamate to form glutamine and use as a transport mechanism
Transport ammonia by alanine-glucose cycle and Gln regeneration
Excrete nitrogenous waste through urea cycle

27. Transportation of ammonia
alaninie - glucose cycle *
regenerate Gln

28. Alanine-Glucose cycle
In the liver alanine transaminase tranfers the ammonia to α-KG and regenerates pyruvate. The pyruvate can then be diverted into gluconeogenesis. This process is refered to as the glucose-alanine cycle.

29. Gln regeneration

30. Urea synthesis Synthesis in liver (Mitochondria and cytosol)
Excretion via kidney
To convert ammonia to urea for final excretion

31. The urea cycle： 线粒体 尿素 胞 液 CO2 + NH3 + H2O 氨基甲酰磷酸 Pi 瓜氨酸 鸟氨酸 瓜氨酸 氨基酸
2ADP+Pi
CO2 + NH3 + H2O
氨基甲酰磷酸
2ATP
N-乙酰谷氨酸
线粒体 Pi
鸟氨酸
瓜氨酸
精氨酸代
琥珀酸
瓜氨酸
天冬氨酸
ATP
AMP + PPi
氨基酸
草酰乙酸
苹果酸
α-酮戊 二酸
谷氨酸
α-酮酸
鸟氨酸 尿素
精氨酸
延胡索酸
胞 液

32. UREA CYCLE (liver) 1. Overall Reaction:
NH3 + HCO3– + aspartate + 3 ATP + H2O  urea +
fumarate + 2 ADP + 2 Pi + AMP + ppi
2. Requires 5 enzymes:
2 from mitochondria and 3 from cytosol

33. Regulation of urea cycle
The intake of the protein in food：the intake↑↑urea synthesis
AGA：CPS I is an allosteric enzyme sensitive to activation by N-acetylglutamate（AGA） which is derived from glutamate and acetyl-CoA.
All intermediate products accelerate the reaction
Rate-limiting enzyme of urea cycle is argininosuccinate synthetase(精氨酸代琥珀酸合成酶)

34. The Urea Cycle is Linked to the Citric Acid Cycle
NH4+

35. III. Biosynthesis of Amino acids

36. Ammonium Ion Is Assimilated into Amino Acids Through Glutamate and Glutamine
Major Ammonium ion carrier

37. Biosynthesis of Amino Acids