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Enzymatic Degradation of Bradykinin
Published in Sami I. Said, Proinflammatory and Antiinflammatory Peptides, 2020
Randal A. Skidgel, Ervin G. Erdös
Carboxypeptidases cleave the C-terminal amino acid of peptides and proteins. Carboxypeptidases involved in Bk metabolism can be divided into two groups, the serine carboxypeptidases and the metallocarboxypeptidases. Most investigations have focused on the role of metallocarboxypeptidases, as, historically, carboxypeptidase N was the first human kininase discovered (Erdös and Sloane, 1962).
The Small IntestineSecretions, Digestion and Motility
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Proteins found in the intestines are derived from endogenous sources (secretory proteins and desquamated cells) and exogenous proteins (dietary protein). Although 10%–15% of protein in the gastrointestinal tract is digested by gastric pepsin, protein digestion products in the stomach are important because they stimulate the secretion of proteases by the pancreas. Most protein digestion results from the actions of pancreatic proteolytic enzymes. Trypsinogen and chymotrypsinogen are activated by enterokinase or by autocatalysis with trypsin. Trypsin and chymotrypsin, which are endopeptidases, cleave internal peptide linkages to produce dipeptides, tripeptides and other small peptide chains that can be absorbed by intestinal cells. Carboxypeptidase (exopeptidase) is also produced by the pancreas and intestinal epithelial cells. Carboxypeptidases cleave the ends of a peptide chain, producing free amino acids, which are readily absorbed by the intestine. The last step in the digestion of protein is achieved by enterocytes that line the villi. At the brush border, aminopeptidases split larger polypeptides into tripeptides, dipeptides and some amino acids. These are transported into the enterocytes where multiple peptidases digest the dipeptides and tripeptides to amino acids, which then enter the blood.
The Renin-Angiotensin System
Published in Austin E. Doyle, Frederick A. O. Mendelsohn, Trefor O. Morgan, Pharmacological and Therapeutic Aspects of Hypertension, 2020
However, very high concentrations of angiotensin I may be handled in a different manner.251 Using near-physiological concentrations of angiotensin I injected into the pulmonary arteries of anesthetized rats, only angiotensin II and unaltered angiotensin I were found in the pulmonary venous effluent, indicating the action of converting enzyme. However, when higher doses of angiotensin I were administered, the converting enzyme appeared to become saturated, and a peptide resembling [des-Leu10]-angi-otensin I was found in the venous effluent in large quantities. The appearance of this peptide fragment indicates the action of a carboxypeptidase. The authors suggested that this dual enzyme system might allow protective inactivation of excessive amounts of angiotensin I reaching the lungs.
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
Carboxypeptidases (EC 3.4.16–3.4.18) are peptidases that cleave a peptide bond at the carboxy-terminal (C-terminal) end of a peptide or protein. Carboxypeptidases are named with a combination of one letter and one number following the word carboxypeptidase at the beginning. There are at least 17 carboxypeptidases, belonging to two major groups. One uses serine as an active site residue named as serine carboxypeptidases, and the other uses zinc at the active site, known as metallocarboxypeptidases, which are further separated into two subgroups based on amino acid sequence similarities [66]. Among the carboxypeptidases, some of them have low tissue specificity with expression in many tissues and are secreted into bodily fluids with a low concentration, such as carboxypeptidases D and X2. Some are in specific tissues without leaking into bodily fluids or with a low concentration in bodily fluids, such as carboxypeptidase A4 in the esophagus and skin, carboxypeptidase A6 in the intestine, prostate, and retina, carboxypeptidase E in the brain, carboxypeptidase M in the adipose, carboxypeptidase O in the intestine, X1 in the placenta, and carboxypeptidase Z in the ovary. And others are produced in specific tissues and then secreted into either small intestinal fluid or blood. Carboxypeptidases A1, A2, and B1 are produced in the pancreas and activated in the duodenum. All three proteins are zinc-containing metallopeptidases [67]. Compared to the high abundance of trypsin, chymotrypsin and elastase in the small intestine, carboxypeptidases such as A1, A2, and B1, have a much lower concentration.
Endothelialitis plays a central role in the pathophysiology of severe COVID-19 and its cardiovascular complications
Published in Acta Cardiologica, 2021
Christiaan J. M. Vrints, Konstantin A. Krychtiuk, Emeline M. Van Craenenbroeck, Vincent F. Segers, Susanna Price, Hein Heidbuchel
ACE2, a homolog of the angiotensin-converting enzyme (ACE), was discovered 20 years ago [39,42]. This membrane-bound carboxypeptidase is universally present in the cardiovascular system as well as in the lung, intestine, and kidney. It hydrolyses angiotensin II (Ang II) to angiotensin 1–7 (Ang 1–7), which has vasodilator and cardioprotective effects through activation of the MAS receptor, coded by the MAS1 gene (mitochondrial assembly 1) [43,44] (Figure 3). By hydrolysing Ang II to Ang 1–7, ACE2 counterbalances the vasoconstriction induced by activation of the ACE-Ang II-angiotensin receptor 1 (AT1) axis of the RAS. In various diseases where the ACE-Ang II-AT1 axis is activated, ACE2 may mitigate the detrimental effects of Ang II [44]. As a consequence, impairment of the cardioprotective effects the ACE2-Ang [1-7]-MAS axis will accelerate the disease-promoting actions of an activated ACE-Ang II-AT1 axis. Furthermore, excess of Ang II in disease will further weaken the protective role of ACE2 by activating disintegrin and metalloprotease 17 (ADAM17), an enzyme that leads to shedding of the ectodomain of ACE2 from the cell membrane into the circulation [45,46]. A high concentration of this soluble ACE2 is a known marker of an unfavourable prognosis in patients with cardiovascular disease [47].
Is individual genetic susceptibility a link between silica exposure and development or severity of silicosis? A systematic review
Published in Inhalation Toxicology, 2020
Kaio Cezar Rodrigues Salum, Marcos Cesar Santos Castro, Ângela Santos Ferreira Nani, Fabiana Barzotto Kohlrausch
Carboxypeptidase M (CPM) belongs to the family of the carboxypeptidases, which function is removing C-terminal amino acids from peptides and proteins and exert roles in physiological processes like inflammation. CPM has been suggested to play critical roles in inflammatory diseases (Deiteren et al. 2009), and a higher expression level of CPM may promote the progression of lung fibrosis (Chu et al. 2019). In fact, the relative expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls (Chu et al. 2019). Based on the hypothesis that the rs12812500 polymorphism is located on the promoter of the CPM gene and was associated with higher CPM expression, Chu et al. (2019) evaluated this polymorphism and observed the G allele was associated with an increased risk of silicosis in an additive genetic model controlled for confounders.