Prolyl endopeptidase or prolyl oligopeptidase, sometimes post-proline cleaving enzyme) is a large cytosolic enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 that belongs to a distinct class of serine

Serine

Serine is an amino acid with the formula HO2CCHCH2OH. It is one of the proteinogenic amino acids. By virtue of the hydroxyl group, serine is classified as a polar amino acid.-Occurrence and biosynthesis:...

 peptidases. It was first described in the cytosol of rabbit brain as an oligopeptidase

Oligopeptidase

Oligopeptidase is an enzyme that cleaves peptides but not proteins, a property that is due to its structure: the active site of this enzyme is located at the end of a narrow cavity which can only be reached by peptides...

, which degrades the nonapeptide bradykinin

Bradykinin

Bradykinin is a peptide that causes blood vessels to dilate , and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors, which are used to lower blood pressure, increase bradykinin further lowering blood pressure...

 at the Pro-Phe bond. The enzyme is involved in the maturation and degradation of peptide hormones and neuropeptides such as alpha-melanocyte-stimulating hormone

Alpha-Melanocyte-stimulating hormone

alpha-Melanocyte-stimulating hormone , also known as alpha-melanotropin, alpha-melanocortin, or alpha-intermedin, is a naturally-occurring endogenous peptide hormone of the melanocortin family, with a tridecapeptide structure and the amino acid sequence...

, luteinizing hormone-releasing hormone (LH-RH), thyrotropin-releasing hormone

Thyrotropin-releasing hormone

Thyrotropin-releasing hormone , also called thyrotropin-releasing factor , thyroliberin or protirelin, is a tropic tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary...

, angiotensin

Angiotensin

Angiotensin, a peptide hormone, causes blood vessels to constrict, and drives blood pressure up. It is part of the renin-angiotensin system, which is a major target for drugs that lower blood pressure. Angiotensin also stimulates the release of aldosterone, another hormone, from the adrenal cortex...

, neurotensin

Neurotensin

Neurotensin is a 13 amino acid neuropeptide that is implicated in the regulation of luteinizing hormone and prolactin release and has significant interaction with the dopaminergic system...

, oxytocin

Oxytocin

Oxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...

, substance P

Substance P

In the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...

 and vasopressin

Vasopressin

Arginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...

. PREP cleaves peptide bonds at the C-terminal side of proline

Proline

Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...

 residues. Its activity is confined to action on oligopeptides of less than 10 kD and it has an absolute requirement for the trans-configuration of the peptide bond

Peptide bond

This article is about the peptide link found within biological molecules, such as proteins. A similar article for synthetic molecules is being created...

 preceding proline.

Some types of prolyl endopeptidase have been used in studies to decrease the propensity of gluten

Gluten

Gluten is a protein composite found in foods processed from wheat and related grain species, including barley and rye...

-containing wheat

Wheat

Wheat is a cereal grain, originally from the Levant region of the Near East, but now cultivated worldwide. In 2007 world production of wheat was 607 million tons, making it the third most-produced cereal after maize and rice...

 products to aggravate coeliac disease

Coeliac disease

Coeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...

. However, orally administered enzymes are potentially subject to inactivation in the gastrointestinal tract.

In humans prolyl endopeptidase] is encoded by the PREP gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

. The protein encoded by this gene is a cytosolic prolyl endopeptidase that cleaves peptide

Peptide

Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...

 bonds on the C-terminal side of prolyl residues within peptides that are up to approximately 30 amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s long. Prolyl endopeptidases have been reported to be involved in the maturation and degradation of peptide hormone

Hormone

A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

s and neuropeptide

Neuropeptide

Neuropeptides are small protein-like molecules used by neurons to communicate with each other. They are neuronal signaling molecules, influence the activity of the brain in specific ways and are thus involved in particular brain functions, like analgesia, reward, food intake, learning and...

s. There's an indication that altered PREP activity is associated with autism spectrum disorders and various psychological diseases such as schizophrenia

Schizophrenia

Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

, mania

Mania

Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...

 and clinical depression

Clinical depression

Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...

.

Inhibitors

Several prolyl endopeptidase inhibitors are known, and have been suggested as possible nootropic

Nootropic

Nootropics , also referred to as smart drugs, brain steroids, memory enhancers, cognitive enhancers, and intelligence enhancers, are drugs, supplements, nutraceuticals, and functional foods that improve mental functions such as cognition, memory, intelligence, motivation, attention, and concentration...

 and antidepressant

Antidepressant

An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...

 drugs. Notable compounds include

• Baicalin
  Baicalin
  Baicalin is a flavone, a type of flavonoid. It is found in several species in the genus Scutellaria, including Scutellaria lateriflora . There are 10 mg/g baicalin in Scutellaria galericulata leaves...
  
  
• JTP-4819
• KYP-2047
• S-17092
  S-17092
  S-17092 is a drug which acts as a selective inhibitor of the enzyme Prolyl endopeptidase. This enzyme is involved in the metabolic breakdown of a number of neuropeptide neurotransmitters in the brain, and so inhibiting the action of the enzyme increases the activity of these neuropeptides...
  
  
• Berberine
  Berberine
  Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. It is found in such plants as Berberis Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. It is found in such plants as Berberis Berberine is a quaternary...
  
  

External links

• Prolyl Endopeptidase entry at the National Center for Biotechnology Information