Behavioral and neurochemical effects of proline

Metab Brain Dis. 2011 Sep;26(3):159-72. doi: 10.1007/s11011-011-9246-x. Epub 2011 Jun 4.


Proline is an amino acid with an essential role for primary metabolism and physiologic functions. Hyperprolinemia results from the deficiency of specific enzymes for proline catabolism, leading to tissue accumulation of this amino acid. Hyperprolinemic patients can present neurological symptoms and brain abnormalities, whose aetiopathogenesis is poorly understood. This review addresses some of the findings obtained, mainly from animal studies, indicating that high proline levels may be associated to neuropathophysiology of some disorders. In this context, it has been suggested that energy metabolism deficit, Na(+),K(+)-ATPase, kinase creatine, oxidative stress, excitotoxicity, lipid content, as well as purinergic and cholinergic systems are involved in the effect of proline on brain damage and spatial memory deficit. The discussion focuses on the relatively low antioxidant defenses of the brain and the vulnerability of neural tissue to reactive species. This offers new perspectives for potential therapeutic strategies for this condition, which may include the early use of appropriate antioxidants as a novel adjuvant therapy, besides the usual treatment based on special diets poor in proline.

Publication types

  • Review

MeSH terms

  • 1-Pyrroline-5-Carboxylate Dehydrogenase / deficiency
  • Amino Acid Metabolism, Inborn Errors / metabolism
  • Animals
  • Antioxidants* / metabolism
  • Antioxidants* / therapeutic use
  • Ascorbic Acid / therapeutic use
  • Brain / metabolism
  • Brain Diseases, Metabolic* / chemically induced
  • Brain Diseases, Metabolic* / metabolism
  • Creatine Kinase / metabolism
  • Energy Metabolism / physiology*
  • Free Radicals / adverse effects*
  • Glycine / metabolism
  • Glycine / urine
  • Gyrate Atrophy / metabolism
  • Humans
  • Memory Disorders* / chemically induced
  • Memory Disorders* / metabolism
  • Mice
  • Oxidative Stress / physiology*
  • Proline Oxidase / deficiency
  • Proline Oxidase / metabolism
  • Proline* / adverse effects
  • Proline* / metabolism
  • Rats
  • Receptors, Cholinergic / metabolism
  • Receptors, Purinergic / metabolism
  • Renal Tubular Transport, Inborn Errors / metabolism
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Vitamin E / therapeutic use


  • Antioxidants
  • Free Radicals
  • Receptors, Cholinergic
  • Receptors, Purinergic
  • Vitamin E
  • Proline
  • 1-Pyrroline-5-Carboxylate Dehydrogenase
  • Proline Oxidase
  • Creatine Kinase
  • Sodium-Potassium-Exchanging ATPase
  • Ascorbic Acid
  • Glycine

Supplementary concepts

  • Hyperprolinemia type 2
  • Iminoglycinuria