Synthesis of Polypeptides:
Degradation of proteins to amino acids happens in 3 circumstances:
--During normal synthesis and degredation of cellular proteins.
--When diet is protein-rich and ingested amino acids exceed needs for
protein synthesis-amino acids.
-During starvation or in uncontrolled diabetes, when carbohydrates ae
either unavaialble or imporperly used.
Turnover of cellular proteins:
--Protein turnover: the degrdation and re-synthesis of important
proteins.
--Cell proteins have different half lives: Some proteins are stable, but
many are short lived-half lives vary from minute to the lifetime of a
human. Proetins in eyes are present throughout lifetime while other
proteins have fust turnover(present for minutes) to allow thier qucik
activation or shutdown.
--Cells eliminate a certain amount of proteins because: 1) A significant
proportion of newly synthesised proteins are defective due to errors in
translation or misfolding. 2) Proteins may undergo modification/damage
over the passage of time e.g. due to oxidation and aggregation.
--A number of human pathological conditions are associated with protein
aggregation. e.g. Parkinsons, Huntington diseases
Regulation of Protein turnover:
--Regulation of degradation is dictated by energy requirements of the
cell and organism
--Eukaryotic cells add ubiquitin to proteins that should be destroyed:
Ubiquitin has extended carboxl terminus which gets activated and linked
to protiens that are to be destroyed.
Conjugation of ubiqutin to proteins:
--Ubiquitin is a small highyl conserved protein in eukaryotes. Yeast and
human ubiquitin differs at only 3 of 76 amino acids.
--Carboxyl-terminal glycine of ubiqutin is covalently attached to the
epsilon amino groups of several Lys in the protein.
--Energy required to form the isopeptide bond between the amino group and
ubiqutin is obtained from ATP hydrolysis.
--Three enzymes are used for this conjugation: 1) E1: Ubiquitin-
activating enzyme, 2) E2: Ubiquitin- conjugating enzyme, E3: Ubiqutin-
protein ligase.
Proteasome:
--After cojugation of ubiquitin to the protein, a protease enzyme called
proteasome digeets the proteins, which also requires ATP hydrolysis. It
consists of 20S catalytic nd 19S regulatory subunits.
--The 20s catalytic subunits comprises of 28 homologous subunits arranges
in 4 rings each contaning 7 subunits. Some Beta-subunits include protease
active sites at their amino terminal
-- Two 19s complexes bind to each of the 20s core, to form the complete
26s proteasome.
--The 19s subunit has 3 functions:
1)Binds specifically to ubiquitin chains
Degradation of proteins to amino acids happens in 3 circumstances:
--During normal synthesis and degredation of cellular proteins.
--When diet is protein-rich and ingested amino acids exceed needs for
protein synthesis-amino acids.
-During starvation or in uncontrolled diabetes, when carbohydrates ae
either unavaialble or imporperly used.
Turnover of cellular proteins:
--Protein turnover: the degrdation and re-synthesis of important
proteins.
--Cell proteins have different half lives: Some proteins are stable, but
many are short lived-half lives vary from minute to the lifetime of a
human. Proetins in eyes are present throughout lifetime while other
proteins have fust turnover(present for minutes) to allow thier qucik
activation or shutdown.
--Cells eliminate a certain amount of proteins because: 1) A significant
proportion of newly synthesised proteins are defective due to errors in
translation or misfolding. 2) Proteins may undergo modification/damage
over the passage of time e.g. due to oxidation and aggregation.
--A number of human pathological conditions are associated with protein
aggregation. e.g. Parkinsons, Huntington diseases
Regulation of Protein turnover:
--Regulation of degradation is dictated by energy requirements of the
cell and organism
--Eukaryotic cells add ubiquitin to proteins that should be destroyed:
Ubiquitin has extended carboxl terminus which gets activated and linked
to protiens that are to be destroyed.
Conjugation of ubiqutin to proteins:
--Ubiquitin is a small highyl conserved protein in eukaryotes. Yeast and
human ubiquitin differs at only 3 of 76 amino acids.
--Carboxyl-terminal glycine of ubiqutin is covalently attached to the
epsilon amino groups of several Lys in the protein.
--Energy required to form the isopeptide bond between the amino group and
ubiqutin is obtained from ATP hydrolysis.
--Three enzymes are used for this conjugation: 1) E1: Ubiquitin-
activating enzyme, 2) E2: Ubiquitin- conjugating enzyme, E3: Ubiqutin-
protein ligase.
Proteasome:
--After cojugation of ubiquitin to the protein, a protease enzyme called
proteasome digeets the proteins, which also requires ATP hydrolysis. It
consists of 20S catalytic nd 19S regulatory subunits.
--The 20s catalytic subunits comprises of 28 homologous subunits arranges
in 4 rings each contaning 7 subunits. Some Beta-subunits include protease
active sites at their amino terminal
-- Two 19s complexes bind to each of the 20s core, to form the complete
26s proteasome.
--The 19s subunit has 3 functions:
1)Binds specifically to ubiquitin chains
