- Composition: Proteins consists of a chain of > 100 amino acids (AAs) that are connected through multiple peptide bonds (polypeptide chain).
Structure: broken down into 4 levels
- Primary structure: the sequence of AAs in the polypeptide chain
- Secondary structure: structural folding that occurs based on patterns of H+-bonds between parts of the same polypeptide chain
- Tertiary structure: 3-dimensional structure of secondary structures
- Quaternary structure: 3-dimensional structure of ≥ 2 individual polypeptide chains (subunits) = multimer
- For both tertiary and quarternary, folding driven by: hydrophobic interactions, H+-bonds, salt bridges, disulfide bonds
- Proper protein folding must occur for a protein to be functional (see learning card on translation and protein synthesis)
- Protein synthesis: See learning card on .
- Denaturation: the undoing of correct protein structure
- Duodenum: further cleavage from pancreatic and intestinal proteases
- Absorption of di-, tri-, and tetrapeptides: likely via a proton symporter
- Absorption of single amino acids: via Na+-coupled carrier proteins for specific AA groups (neutral, branched-chain, aromatic, acidic, basic)
- AAs enter bloodstream → liver (via portal vein)
- Zymogens: proteases that are first secreted in an inactive form to avoid damage to the immediate surrounding tissue
|Important proteases of the gastrointestinal tract|
|Endopeptidases: split peptide bonds within the polypeptide chain|| |
|Pancreatic elastase|| |
|Exopeptidases: split peptide bonds from end AAs||Carboxypeptidases: split unspecific end AAs from C-terminal||Carboxypeptidase A|| || |
|Carboxypeptidase B|| |
|Aminopeptidase|| || || |
|Dipeptidase|| || || |
Trypsinogen is first activated by enteropeptidase via proteolytic cleavage at the N-terminal. The resulting trypsin then activates other zymogens, including further trypsinogen (positive feedback loop).
- Description: Proteins are targeted via ubiquitination for degradation in proteasomes.
- Ubiquitination: addition of ubiquitin to the ε-amino group of lysine residues of a substrate protein; it consists of 3 parts
Examples of diseases associated with aberrant proteolysis
There are many diseases associated with aberrant proteolysis; this list is not exhaustive.
- Conditions that lead to increased tissue protein breakdown
Conditions caused by increased protein breakdown
- ; and
- Pancreatitis and possibly resulting
- Malignancy induced cachexia
Conditions caused by accumulation of damaged or misfolded proteins/peptides (see in the learning card on for more details)
- Age-related neurological diseases/neurodegenerative diseases (e.g., Alzheimer disease, Parkinson disease, Huntington disease)
- Prion-related conditions (e.g., Creutzfeldt-Jakob disease)
- Myotonic muscular dystrophy
- Cardiovascular diseases
- Inflammatory responses and autoimmune diseases