Enteropeptidase is an 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...

 produced by cells of the duodenum

Duodenum

The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...

 and involved in human digestion

Digestion

Digestion is the mechanical and chemical breakdown of food into smaller components that are more easily absorbed into a blood stream, for instance. Digestion is a form of catabolism: a breakdown of large food molecules to smaller ones....

. It is secreted from intestinal glands (the crypts of Lieberkühn

Crypts of Lieberkühn

In histology, an intestinal crypt is a gland found in the epithelial lining of the small intestine and colon...

) following the entry of ingested food passing from the stomach. Enteropeptidase converts trypsinogen

Trypsinogen

Trypsinogen is the precursor form or zymogen of the pancreatic enzyme trypsin. It is found in pancreatic juice, along with amylase, lipase, and chymotrypsinogen. It is activated by enteropeptidase, which is found in the intestinal mucosa, to form trypsin. Once activated, the trypsin can activate...

 (a zymogen

Zymogen

A zymogen is an inactive enzyme precursor. A zymogen requires a biochemical change for it to become an active enzyme. The biochemical change usually occurs in a lysosome where a specific part of the precursor enzyme is cleaved in order to activate it...

) into its active form trypsin

Trypsin

Trypsin is a serine protease found in the digestive system of many vertebrates, where it hydrolyses proteins. Trypsin is produced in the pancreas as the inactive proenzyme trypsinogen. Trypsin cleaves peptide chains mainly at the carboxyl side of the amino acids lysine or arginine, except when...

, resulting in the subsequent activation of pancreatic

Pancreas

The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...

 digestive enzymes.

Enteropeptidase is a serine protease

Serine protease

Serine proteases are enzymes that cleave peptide bonds in proteins, in which serine serves as the nucleophilic amino acid at the active site.They are found ubiquitously in both eukaryotes and prokaryotes...

  consisting of a disulfide-linked 82–140 kDa heavy chain which anchors enterokinase in the intestinal brush border membrane and a 35–62 kDa light chain which contains the catalytic subunit. Enteropeptidase is a part of the chymotrypsin

Chymotrypsin

Chymotrypsin is a digestive enzyme that can perform proteolysis. Chymotrypsin preferentially cleaves peptide amide bonds where the carboxyl side of the amide bond is a tyrosine, tryptophan, or phenylalanine. These amino acids contain an aromatic ring in their sidechain that fits into a...

-clan of serine proteases, and is structurally similar to these proteins.

Activity

Despite its alternative name, enteropeptidase is a serine protease which catalyses the hydrolysis of peptide bonds in proteins. Enteropeptidase exhibits trypsin-like activity, cleaving proteins following a lysine at a specific cleavage site (Asp-Asp-Asp-Asp-Lys

Lysine

Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....

). As the pro-region of trypsinogen contains this sequence, enteropeptidase catalyses

Catalysis

Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....

 its activation in vivo:

trypsinogen → trypsin + pro-region (Val

Val

Val is a variant of the feminine given name Valerie.Val may refer to:-Given name:* Val Ackerman , American attorney, former basketball player, and first president of the Women's National Basketball Association* Val A...

-Asp-Asp-Asp-Asp-Lys)

Genetics

In humans, enteropeptidase is encoded by the PRSS7 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...

 (also known as ENTK) on chromosome 21q21. Some nonsense

Nonsense mutation

In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and in a truncated, incomplete, and usually nonfunctional protein product. It differs from a missense mutation, which is a point mutation...

 and frameshift

Frameshift mutation

A frameshift mutation is a genetic mutation caused by indels of a number of nucleotides that is not evenly divisible by three from a DNA sequence...

 mutations in this gene lead to a rare recessive

Recessive

In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...

 disorder characterised by severe failure to thrive in affected infants, due to enteropeptidase deficiency.

Applications

Enteropeptidase's specificity makes it an ideal tool in biochemical applications; a fusion protein containing a C-terminal tag (such as poly-His

Histidine

Histidine Histidine, an essential amino acid, has a positively charged imidazole functional group. It is one of the 22 proteinogenic amino acids. Its codons are CAU and CAC. Histidine was first isolated by German physician Albrecht Kossel in 1896. Histidine is an essential amino acid in humans...

) linked by this sequence can be cleaved by enteropeptidase to obtain the target protein following protein purification

Protein purification

Protein purification is a series of processes intended to isolate a single type of protein from a complex mixture. Protein purification is vital for the characterization of the function, structure and interactions of the protein of interest. The starting material is usually a biological tissue or...

. Alternatively, the N-terminal pro-sequence of proteases which must be cleaved prior to activation can be mutated to enable activation with enteropeptidase.