Proline

Research suggests Proline supports connective tissue health, especially skin and joints, through collagen synthesis.
It seems likely that Proline aids wound healing and muscle preservation, often used in supplements.
The evidence leans toward Proline having neurological effects via NMDA receptors, potentially linked to conditions like hyperprolinemia.
Proline is used in total parenteral nutrition for nutritional support, with metabolic roles in pathways like arginine metabolism.
Proline is a key building block of collagen.
Interestingly, Proline can affect brain cells by interacting with NMDA receptors, which are involved in nerve signaling. While this might contribute to neurological issues in conditions like hyperprolinemia (high Proline levels), its direct therapeutic use in this area is less clear and requires more research.
Proline plays a role in metabolic pathways, such as arginine and proline metabolism, which are important for overall body function.
This is supported by studies indicating topical application may be more effective for wound treatment than oral supplementation (L-Proline: Benefits, Side Effects & Dosage | BulkSupplements).
The quality of Proline supplements is also a consideration, with a study assessing seven dietary supplements finding content variability (73–121% in capsules, 103–156% in tablets) and detecting five contaminants, emphasizing the need for quality control (Dietary Supplements with Proline—A Comprehensive Assessment of Their Quality | PMC).
Proline’s most prominent pharmacological action is its role in collagen synthesis, where it constitutes a significant portion of the glycine-proline-hydroxyproline triplets forming the triple-helical structure of collagens. Clinically, this translates to its use in addressing conditions requiring tissue repair, such as arthritis or post-surgical recovery (L-Proline | Health Benefits and Uses of L-Proline | Xtendlife).
Proline is involved in several metabolic pathways, notably arginine and proline metabolism, which are crucial for energy production and amino acid interconversion. It is a substrate for Proline dehydrogenase 1, mitochondrial (PRODH), which converts Proline to delta-1-pyrroline-5-carboxylate, a step in its catabolism. This enzyme’s activity is linked to cell proliferation and tumor development, suggesting Proline’s role in metabolic stress responses, particularly in cancer cells (Proline Dehydrogenase - an overview | ScienceDirect Topics).
At the molecular level, Proline binds to peptidyl-prolyl cis-trans isomerases (e.g., PPIB, PPIA), enzymes that catalyze the cis-trans isomerization of proline imidic peptide bonds, influencing protein folding and conformation. This action is significant for structural proteins like collagen. Additionally, Proline inhibits monocarboxylate transporter 10 (SLC16A10), which transports thyroid hormones and aromatic acids, potentially affecting hormonal and metabolic regulation (Proline: Uses, Interactions, Mechanism of Action | DrugBank Online).
A study on CA1 hippocampal pyramidal cells demonstrated that L-Proline induces depolarization, primarily via postsynaptic NMDA receptor activation, leading to multiple orthodromic population spikes and potential depolarization block. This action suggests neuroexcitatory and neurotoxic potential, with implications for conditions like hyperprolinemia, where elevated Proline levels may contribute to seizures and mental retardation (NMDA receptor-mediated depolarizing action of proline on CA1 pyramidal cells | ScienceDirect).
Additionally, defects in neural Proline transport, mediated by transporters like SLC6A7 (PROT1) and SLC6A19 (B0AT1), are associated with ataxia and psychosis. Genetic or pharmacological inhibition of SLC6A7 has been shown to reduce locomotor activity and improve learning and memory in mice, highlighting Proline’s role in cognitive and motor functions (Frontiers | The Multifaceted Roles of Proline in Cell Behavior).
Proline’s role in pathology is notable, particularly in parasitic infections. For instance, in Trypanosoma cruzi (the causative agent of Chagas disease), Proline is essential for survival under oxidative and thermal stress, and inhibiting its uptake is explored as a novel drug target, with studies developing transporter inhibitors to reduce parasite proliferation (Frontiers | Targeting L-Proline Uptake as New Strategy for Anti-chagas Drug Development).
In cancer, increased Proline metabolism is observed in metastatic cell lines, correlating with invasiveness and resistance to oxidative stress, suggesting its role in tumor progression (Proline Dehydrogenase - an overview | ScienceDirect Topics).

Molecular Target/Interaction	Description
Peptidyl-prolyl cis-trans isomerase B	Binds, affects protein folding, crucial for collagen structure.
Peptidyl-prolyl cis-trans isomerase A	Binds, influences protein conformation, supports structural integrity.
Proline dehydrogenase 1, mitochondrial.	Substrate, converts Proline to delta-1-pyrroline-5-carboxylate, metabolic role.
Monocarboxylate transporter 10	Inhibited, affects thyroid hormone and aromatic acid transport.