Proline (Pro), also known as L-proline is an alpha-amino acid. These are amino acids in which the amino group is attached to the carbon atom immediately adjacent to the carboxylate group (alpha carbon).  Amino acids are organic compounds that contain amino (‚ÄìNH2) and carboxyl (‚ÄìCOOH) functional groups, along with a side chain (R group) specific to each amino acid. Proline is one of 20 proteinogenic amino acids, i.e., the amino acids used in the biosynthesis of proteins. Proline is found in all organisms ranging from bacteria to plants to animals.  It is classified as an aliphatic, non-polar amino acid. Proline is sometimes called an imino acid, although the IUPAC definition of an imine requires a carbon-nitrogen double bond. Proline is a non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. Proline is derived from the amino acid L-glutamate in which glutamate-5-semialdehyde is first formed by glutamate 5-kinase and glutamate-5-semialdehyde dehydrogenase (which requires NADH or NADPH). This semialdehyde can then either spontaneously cyclize to form 1-pyrroline-5-carboxylic acid, which is reduced to proline by pyrroline-5-carboxylate reductase, or turned into ornithine by ornithine aminotransferase, followed by cyclization by ornithine cyclodeaminase to form proline. L-Proline has been found to act as a weak agonist of the glycine receptor and of both NMDA and non-NMDA ionotropic glutamate receptors. It has been proposed to be a potential endogenous excitotoxin/neurotoxin. Studies in rats have shown that when injected into the brain, proline non-selectively destroys pyramidal and granule cells (PMID: 3409032 ). Therefore, under certain conditions proline can act as a neurotoxin and a metabotoxin. A neurotoxin causes damage to nerve cells and nerve tissues. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of proline are associated with at least five inborn errors of metabolism, including hyperprolinemia type I, hyperprolinemia type II, iminoglycinuria, prolinemia type II, and pyruvate carboxylase deficiency. People with hyperprolinemia type I often do not show any symptoms even though they have proline levels in their blood between 3 and 10 times the normal level. Some individuals with hyperprolinemia type I exhibit seizures, intellectual disability, or other neurological or psychiatric problems. Hyperprolinemia type II results in proline levels in the blood between 10 and 15 times higher than normal, and high levels of a related compound called pyrroline-5-carboxylate. Hyperprolinemia type II has signs and symptoms that vary in severity and is more likely than type I to involve seizures or intellectual disability.