Prolyl endopeptidase (PEP)
Synopsis
Prolyl endopeptidase (PEP), also known as prolyl oligopeptidase (POP), is a serine protease enzyme that specifically cleaves peptide bonds at the carboxyl side of proline residues in small peptides (typically under 30 amino acids in length). It is found in various tissues, especially in the brain, liver, and kidneys, and plays a critical role in the breakdown of proline-rich peptides, many of which are neuroactive or regulatory in nature.
PEP is of particular interest in the fields of neurology, digestion, and gluten metabolism. In the central nervous system, PEP is involved in processing neuropeptides such as substance P, vasopressin, oxytocin, and thyrotropin-releasing hormone, which influence mood, memory, learning, and cognitive function. Altered PEP activity has been linked to neurodegenerative diseases such as Alzheimer’s and Parkinson’s, as well as psychiatric conditions including depression and schizophrenia.
In the digestive system, PEP enzymes have gained attention for their ability to break down gluten peptides, particularly the proline-rich sequences in gliadin that are resistant to human digestive enzymes. As such, PEP supplementation has been studied as a potential aid for individuals with non-celiac gluten sensitivity or for reducing gluten exposure in low-gluten diets.
PEP supplements are sometimes marketed for digestive support, cognitive enhancement, and gluten degradation, often in combination with other enzymes.
Historical Use in Medicine:
Prolyl endopeptidase was first isolated in the 1970s from pig kidney and later from various bacterial and human tissues. Its discovery opened new avenues in understanding how short neuropeptides are processed and in exploring the biochemical underpinnings of cognitive and psychiatric disorders.
Though PEP is a relatively modern biochemical discovery, its functions mirror ancient health goals—namely, improving mental clarity, digestion, and resilience to food sensitivities. Modern supplement formulations containing PEP represent a biotechnological advancement, not a traditional herbal or food-based remedy.
In recent years, engineered PEP variants from microbes (e.g., Aspergillus niger, Sphingomonas capsulata) have been included in enzyme blends designed to help hydrolyze gluten in digestive tracts. These have shown promise in clinical trials as adjunctive tools for managing gluten intolerance, though not as a treatment for celiac disease.
Uses: Health Conditions
Alzheimer's Disease (Neither)
Autism (Neither)
Depression (Neither)
Dementia (Neither)
Memory and Brain Function (Scientific)
Post Traumatic Stress Disorder (Neither)
Schizophrenia (Neither)
Body Systems
Digestive System (Science)
Gastrointestinal Tract (Science)
Intestinal System (Science)
Nerves (Science)
Brain (Traditional)
Liver (Traditional)
Small Intestines (Traditional)