Introduction
Shayne C. Gad in Toxicology of the Gastrointestinal Tract, 2018
Protein digestion starts in the stomach, where proteins are fragmented into peptides by the action of pepsin. Enzymes in pancreatic juice—trypsin, chymotrypsin, carboxypeptidase, and elastase—continue to break down proteins into peptides. Although all these enzymes convert whole proteins into peptides, their actions differ somewhat because each splits peptide bonds between different amino acids. Trypsin, chymotrypsin, and elastase all cleave the peptide bond between a specific amino acid and its neighbor; carboxypeptidase breaks the peptide bond that attaches the terminal amino acid to the carboxyl (acid) end of the peptide. Protein digestion is completed by two peptidases in the brush border: aminopeptidase and dipeptidase. Aminopeptidase acts on peptides by breaking the peptide bond that attaches the terminal amino acid to the amino end of the peptide. Dipeptidase splits dipeptides into single amino acids.
Peptidases and Neuropeptide-Inactivating Mechanisms in the Circulation and in the Gastrointestinal Tract
Edwin E. Daniel in Neuropeptide Function in the Gastrointestinal Tract, 2019
Table 5 illustrates the distribution of the peptidases that were either detected or purified from seven organs of the gastrointestinal tract. From a qualitative point of view, most of these organs exhibit a rich peptidasic content. Aminopeptidase B was detected fluorimetrically in all organs of the rat gastrointestinal tract56 as well as in the porcine jejunum.57 In the rat, this peptidase appeared to be abundant in the small intestine (duodenum, jejunum, and ileum), with a specific activity (Vmax≃ 556 nmol of 7AMC released per hour per milligram of protein) that was three- to fivefold higher than in the other organs.56 Interestingly, the distribution of this enzyme paralleled that observed for aminopeptidase N, which was detected in high amounts in the rat small intestine,56 while it was present in 20- to 30- fold lower amounts in the other organs.56 These data corroborated previous studies showing that the highest level of specific activity of this enzyme was recovered in the distal part of the ileum.58 Furthermore, immunohistochemical localization of aminopeptidase M had revealed that the peptidase was mainly present in the rat small gut, with stain particularly concentrated at the entire luminal surface.59
Peptidases and Peptides at the Blood-Brain Barrier
Gerard O’Cuinn in Metabolism of Brain Peptides, 2020
Several aminopeptidases with closely related activities are known to exist. They cleave either the first or second peptide bond of polypeptide chains to release the N-terminal amino acid or dipeptide. The former types are considered in this section. Identification of individual aminopeptidases may be hampered by their broad and sometimes overlapping substrate specificities and sensitivity to inhibitors. They are metalloenzymes, generally Zn2+-dependent, although aminopeptidase A is activated by Ca2+. They occur widely in mammalian systems and may be cytosolic or membrane bound (for a review of their occurrence in humans see ref. 124). The activity of aminopeptidases A and N have been measured in microvessels isolated from brain (see below) and aminopeptidase W, which shows a preference for Trp at position 2 of peptide substrates, has been detected in porcine brain microvessels by immunostaining.125 It is of interest that aminopeptidases A and N may be associated with pericytes of the BBB (see below). An enzyme described as leucine aminopeptidase has been detected in brain capillaries.126
Proteomic response in Streptococcus gordonii DL1 biofilm cells during attachment to salivary MUC5B
Published in Journal of Oral Microbiology, 2021
Carolina Robertsson, Gunnel Svensäter, Zoltan Blum, Magnus E Jakobsson, Claes Wickström
Another protein identified only in the biofilm cultures was the membrane dipeptidase AbpB. This proteolytic protein is a hydrolase that acts as an aminopeptidase by cleaving single amino acids off the substrate protein N-terminal [27]. The AbpB polypeptide contains a signal peptide that is cleaved off before the protein is exported [34]. In S. gordonii, AbpB interacts with salivary amylase together with the amylase-binding protein AbpA. Based on sequence analysis, AbpA seems to be unique to S. gordonii, while AbpB shares sequence homology with other bacterial dipeptidases [34]. Both AbpA and AbpB seem to be involved in attachment during S. gordonii biofilm formation [35], however, related to its proteolytic activity, it has been suggested that AbpB also has a role in the acquisition of amino acids from environmental proteins [34].
Recent advances in proteolytic stability for peptide, protein, and antibody drug discovery
Published in Expert Opinion on Drug Discovery, 2021
Xianyin Lai, Jason Tang, Mohamed E.H. ElSayed
In contrast to carboxypeptidases, aminopeptidases cleave peptide bonds at the N-terminus of proteins. They are widely distributed in many organs and found in many subcellular organelles, cytoplasms, and as membrane components. Aminopeptidases are classified by multiple criteria. Depending on the number of amino acids cleaved from the N-terminus, enzymes that remove one NH2-terminal amino acid are called aminopeptidases, enzymes that remove two NH2-terminal amino acids are called dipeptidyl peptidases, and enzymes that remove three NH2-terminal amino acids are called tripeptidyl peptidases. Based on which residues are removed, aminopeptidases are classified as alanyl, arginyl, aspartyl, cystinyl, leucyl, glutamyl, and methionyl aminopeptidase. Other factors, such as location, pH, susceptibility to inhibition, metal ion content, etc. are applied to category aminopeptidases [69].
Lack of Associations between Endoplasmic Reticulum Aminopeptidase 2 Gene Polymorphisms and Ankylosing Spondylitis: A Meta-analysis with Trial Sequential Analysis
Published in Immunological Investigations, 2022
Shutao Gao, Tao Xu, Chao Mao, Jie Cheng, Chuanhui Xun, Weidong Liang, Weibin Sheng
The ERAP1 and ERAP2 aminopeptidases are intracellular enzymes encoded by ERAP1 and ERAP2, which are neighboring genes structured in an opposite orientation on chromosome 5q15. The protein sequences of ERAP2 and ERAP1 are 49% identical (Brown et al. 2016). Despite substantial work that has been done, the precise mechanism by which aminopeptidases influence AS is still largely undefined. Both of the two aminopeptidases serve as molecular rulers in trimming peptides to suitable lengths before presentation by HLA-I molecules. ERAP2 may act in concert with ERAP1, and dimerization of ERAP1-ERAP2 considerably increases peptide-trimming efficiency (Evnouchidou et al. 2014; Lorente et al. 2013). Chen et al. reported that the ERAP1/ERAP2 heterodimer could work as a peptide editor by trimming substrates into optimal sizes, thus allowing the MHC-I groove to reach a closed conformation (Chen et al. 2016). Besides, ERAP2 can mediate the expression and activity of ERAP1, as well as modify the peptidome (Paladini et al. 2019a).