Proteins and peptides

Summary

Proteins are large biomolecules consisting of more than 50 amino acids connected by multiple peptide bonds, while peptides are small biomolecules consisting of less than 50 amino acids. Proteins fulfill a variety of functions, including regulating physiological activity and providing structure to cells, and their functions are closely tied to their conformation. After ingestion, dietary proteins are denatured by gastric acid and subsequently cleaved by pepsin and proteases into monopeptides, dipeptides, tripeptides, and tetrapeptides. These end products are absorbed in the small intestine via proton symporter and Na+-coupled carrier proteins. Intracellularly, endogenous proteins are degraded by the ubiquitin proteasome system, while endocytosed dietary proteins are degraded by the lysosome. Accumulation of damaged or misfolded proteins/peptides has been observed in many neurological diseases such as Alzheimer disease, Parkinson disease, Huntington disease, Creutzfeldt-Jakob disease, and myotonic muscular dystrophy.

Protein structure

References:[1]

Digestion and absorption of dietary proteins

  • Zymogens: proteases that are first secreted in an inactive form to avoid damage to the immediate surrounding tissue
Important proteases of the gastrointestinal tract
Proteases Location Reaction Product
Endopeptidases: split peptide bonds within the polypeptide chain

Pepsin

Trypsin

  • Oligopeptides
Chymotrypsin
  • Oligopeptides

Pancreatic elastase
  • Oligopeptides
Exopeptidases: split peptide bonds from end AAs Carboxypeptidases: split unspecific end AAs from C-terminal Carboxypeptidase A
  • Activated from zyinomogen procarboxypeptidase A by trypsin
  • Cleaves bonds involving aromatic AAs
  • AAs
Carboxypeptidase B
  • Activated from zymogen procarboxypeptidase B by trypsin
  • Cleaves bonds involving basic AAs
  • AAs
Aminopeptidase
  • Intestinal mucosa
  • Cleaves unspecific end AAs from N-terminal
  • AAs
Dipeptidase
  • Intestinal mucosa
  • Cleaves dipeptides
  • AAs

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).

The inactive zymogen pepsinogen is activated to pepsin by gastric acid.

References:[2][3][3][4][5][6][7]

Protein degradation and associated diseases

Protein degradation

Endogenous proteins (those synthesized in cells) are degraded by proteasomes. Exogenous proteins are degraded by lysosomes.

Ubiquitin proteasome system (UPS)

Some cases of Parkinson disease have been linked to defects in the ubiquitin proteasome system.

Lysosomes

Examples of diseases associated with aberrant proteolysis

There are many diseases associated with aberrant proteolysis; this list is not exhaustive.

References:[8]

  • 1. Rapley R, Whitehouse D. Molecular Biology and Biotechnology. Royal Society of Chemistry; 2015.
  • 2. Hall JE. Guyton and Hall Textbook of Medical Physiology. Philadelphia, PA: Elsevier; 2016.
  • 3. Blackman D. The Logic of Biochemical Sequencing. CRC Press; 1993.
  • 4. Berg JM, Tymoczko JL, Stryer L. Biochemistry. W H Freeman & Company; 2002.
  • 5. Feher JJ. Quantitative Human Physiology. Academic Press; 2017.
  • 6. Barrett KE, Barman SM, Boitano S, Brooks HL. Ganong's Review of Medical Physiology (Enhanced EB). New York, NY: McGraw Hill Professional; 2009.
  • 7. Chatterjea M, Shinde R. Textbook of Medical Biochemistry. New Delhi, India: JP Medical Ltd; 2011.
  • 8. Cooper GM. The Cell: A Molecular Approach. Sunderland, MA: Sinauer Associates; 2000.
  • Kaplan. USMLE Step 1 Lecture Notes 2016: Physiology. Kaplan Publishing; 2015.
last updated 02/25/2020
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