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12/11/23 Metabolism of Proteins Le Thi Hong Nhung, PhD
Department of Biochemistry and Molecular Biology, HUS 1 Contents
I. Protein synthesis and degradation
II. Amino acid synthesis and degradation 2 1 12/11/23 1. Translation: Synthesis of protein 3 4 2 12/11/23
Genetic code: A codon is a triplet of nucleotides 42= 16 different combination 43= 64 different combination 5 Genetic code: Degeneracy 6 3 12/11/23 Genetic code: Degeneracy 7 Genetic code: Universal 8 4 12/11/23 9 Genetic code: non-overlaping Không gối l ên nhau 10 5 12/11/23
Genetic code: non-skipping Đọc l i ền mạch 11
Genetic code: read from 5-3Õ chi u ề đọc 5' -> 3' 12 6 12/11/23
Genetic code: mutant resistant Kháng đ t ộ bi ến 13
Translational Frameshifting and RNA Editing Affect How the Code Is Read
Quá trình dịch khung và sửa đổi RNA
Chuyển dịch khung đọc t o
ạ RNA khác nhau ( vi khuẩn) 14 7 12/11/23
RNA editing: deamination reactions Loại Ami n 15 RNA editing Nêu các đ c ặ điểm của mã di t r uyền ( 8) 16 8 12/11/23 Summary Mã bộ 3 không đã nghÿa thoái hóa không gối l i ên t c ụ kháng đ t ộ bi n ế đọc theo chi u ề 5' - 3' 17
tein Biosynthesis Takes Place in Five ges 18 9 12/11/23 19 Initiation of p ukaryotes 1. Yếu t ố dịch mã 2. Liên kết mRNA 3. Elongation -> Hình thành liên kết peptide 4. 20 10 12/11/23 Elongation Kéo dài 21 Elongation
Kết t húc khi hì nh t hành l i ên k t ế pept i de 22 11 12/11/23 Elongation 23 Termination Dừng 24 12 12/11/23 Summary 25 2. Protein Degradation Phân gi ải protein 26 13 12/11/23 27 Digestion of Dietary Protein
• Proteins are hydrolyzed into small
peptides in the stomach by pepsin.
• Proteins and larger peptides are
cut into smaller peptides in the small intestine by trypsin and chymotrypsin. • Small peptides are further
hydrolyzed into amino acids in the
small intestine by aminopeptidase and carboxypeptidases A and B. 28 14 12/11/23 Digestion of Dietary Protein
• Proteins are hydrolyzed into small
peptides in the stomach by pepsin.
• Proteins and larger peptides are
cut into smaller peptides in the small intestine by trypsin and chymotrypsin. • Small peptides are further
hydrolyzed into amino acids in the
small intestine by aminopeptidase and carboxypeptidases A and B. 29 Action of Proteolytic Enzymes In Small Intestine ez: Phân cắt v t ị rí khác nhau 30 15 12/11/23
Activation of gastric and pancreatic zymogens 31 Absorption of Amino Acids
• Free amino acids are taken into the
enterocytes by a Na+ linked secondary transport system. Phân cách v d ề ng ạ đơn phân
• Di- and tripeptides are taken up by a H+
linked transport system. The peptides are
hydrolyzed in the cytosol to AAs that are released into the portal system by facilitated diffusion.
• Only free amino acids are found in the
portal vein after a meal containing protein. 32 16 12/11/23
Transport of amino acids into cells
• The concentration of free amino acids in the
extracellular fluids is significantly lower than that within the cells. •
This concentration gradient is maintained because
active transport systems, driven by the hydrolysis of ATP
• At least seven different transport systems are
known that have overlapping specificities for different amino acids.
• The small intestine and, the proximal tubule of the
kidney have common transport systems for amino acid uptake.
Bröer, Physiology 23: 95–102008 33 34 17 12/11/23
Protein digesstion in the cells Autophasy + Lysosome
• Lysosomes (20%) Bào quan bên trong t ế bào
Ð Receptor mediated endocytosis & phagocytosis
• Proteasomes (80%): for endogenous proteins Ð transcription factors Ð cell cycle cyclins Ð virus coded proteins Ð improperly folded proteins Ð damaged proteins 35
Protease involved in protein degradation 36 18 12/11/23
Autophagy and lysosome for protein degradation 37 Uibiquitin-Proteasome Pathway like 1 nhà máy c t ắ protein
Ubiquitin is a small protein (76 amino acids) 38 19 12/11/23 39 Đính ubiquitin vào target protein
• Many proteins that contain regions rich in the amino acids proline (P),
glutamate (E), serine (S), and threonine (T) have short half-lives.
Thời gi an t ồn t ại ngắn
• Most of the proteins that contain PEST sequences are hydrolyzed by the ubiquitinÐproteasome system. 40 20