Peptidases, also known as proteases, are enzymes that act as molecular scissors within biological systems. They catalyze the hydrolysis of peptide bonds, which link amino acids in protein and peptide chains. This process, termed proteolysis, involves adding a water molecule to break the bond. By breaking these connections, peptidases dismantle proteins into smaller fragments or individual amino acids.
The Role of Peptidases in Digestion
Protein digestion begins in the stomach, where the acidic environment denatures dietary proteins. Here, the peptidase pepsin, secreted as an inactive precursor called pepsinogen, becomes active at a low pH (1.5-3.5). Pepsin initiates the breakdown of large proteins into smaller polypeptide chains, cleaving bonds near aromatic amino acids like phenylalanine and tryptophan.
As these partially digested proteins move into the small intestine, pancreatic peptidases take over. The pancreas releases inactive forms of enzymes such as trypsinogen and chymotrypsinogen, which are activated by enterokinase. Trypsin cleaves peptide bonds after basic amino acids like lysine and arginine, while chymotrypsin targets aromatic amino acids. These enzymes break down polypeptides into smaller oligopeptides and dipeptides.
The final stages of protein digestion occur at the brush border of the small intestine, where specialized peptidases reside. Aminopeptidases remove individual amino acids from the amino-terminal end of peptide chains, while carboxypeptidases work from the carboxyl-terminal end. Dipeptidases then break down two-amino acid chains into single amino acids. This ensures proteins are reduced to amino acids, dipeptides, or tripeptides, which are absorbed into the bloodstream.
Classification of Peptidases
Peptidases are categorized based on where they cut a protein or peptide chain. Endopeptidases cleave peptide bonds within the internal regions of a polypeptide sequence, like cutting a rope in the middle. Examples include pepsin in the stomach and trypsin in the small intestine.
Conversely, exopeptidases remove amino acids from the ends of a protein or peptide chain, similar to trimming strands from a rope’s end. They are divided into aminopeptidases, which remove amino acids from the N-terminal (amino end), and carboxypeptidases, which remove them from the C-terminal (carboxyl end). These enzymes aid the final digestion of small peptides into individual amino acids.
Beyond their cleavage site, peptidases are also classified by their catalytic mechanism, based on the chemical group in their active site. For instance, serine peptidases utilize a serine residue for catalysis. Metallopeptidases rely on a metal ion at their active site to facilitate bond breaking. These distinct mechanisms allow peptidases to perform their roles with high specificity.
Peptidase Functions Beyond Digestion
Peptidases contribute to many processes beyond breaking down food. One role is in blood clotting, where specific serine peptidases are involved. For example, thrombin, a serine peptidase, converts fibrinogen into fibrin, which forms the meshwork of a blood clot. This action is tightly regulated to prevent excessive bleeding or unwanted clot formation.
Peptidases also participate in the body’s immune responses. They can break down foreign proteins from bacteria or viruses. Certain peptidases activate immune cells or process antigens for presentation, helping the immune system recognize and eliminate threats.
Another function is cellular protein turnover, involving the continuous recycling of proteins within cells. Peptidases in lysosomes and the cytosol degrade these proteins into amino acids for reuse. This breakdown and synthesis ensures cellular health and adaptation. The ubiquitin-proteasome system is a pathway for this intracellular recycling.
Medical and Therapeutic Significance
Dysregulation of peptidase activity can contribute to various diseases. An imbalance in pancreatic peptidase activity, for example, can lead to pancreatitis, an inflammation. This condition may arise if digestive enzymes activate prematurely within the pancreas, causing self-digestion of its tissues.
Beyond malfunctions, peptidases are also targets for therapeutic interventions. A prominent example is Angiotensin-Converting Enzyme (ACE) inhibitors, used to manage high blood pressure. ACE is a metallopeptidase that converts angiotensin I into angiotensin II, a powerful vasoconstrictor. ACE inhibitors work by blocking this peptidase, preventing angiotensin II formation.
This inhibition relaxes blood vessels, lowering blood pressure and reducing heart workload. These inhibitors also prevent the breakdown of bradykinin, a substance that promotes vasodilation. Modulating peptidase activity in this manner offers an effective strategy for treating cardiovascular conditions.