Activation Effects of Carnosine- and Histidine-Containing Dipeptides on Human Carbonic Anhydrases: A Comprehensive Study.

Published on Mar 4, 2020in International Journal of Molecular Sciences5.924
· DOI :10.3390/IJMS21051761
Giulio Vistoli36
Estimated H-index: 36
(University of Milan),
Giancarlo Aldini65
Estimated H-index: 65
(University of Milan)
+ 3 AuthorsClaudiu T. Supuran155
Estimated H-index: 155
(UniFI: University of Florence)
Sources
Abstract
l-Carnosine (β-Ala-l-His) and several other histidine-containing peptides, including two N-methylated forms on the imidazole ring (l-anserine and l-balenine), two derivatives modified on the carboxyl function (carcinine and l-carnosinamide), two analogues differing in the length of the N-terminal residue (l-homocarnosine and Gly-l-His) and the N-acetyl derivatives, were investigated as activators of four isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The four human isoforms hCA I, II, VA and IX were activated in the low to high micromolar range, with a rather complex structure activity relationship. A performed computational study allowed us to rationalize these results and to propose a binding mode of these activators within the enzyme active site. Similarly to other CA activators, the here studied peptides could find relevant pharmacological applications such as in the management of CA deficiencies, for therapy memory and enhancing cognition or for artificial tissues engineering.
📖 Papers frequently viewed together
19991.43Farmaco
References39
Newest
#1Rossana Occhipinti (Case Western Reserve University)H-Index: 10
#2Walter F. Boron (Case Western Reserve University)H-Index: 80
Carbonic anhydrases (CAs) catalyze a reaction fundamental for life: the bidirectional conversion of carbon dioxide (CO2) and water (H2O) into bicarbonate (HCO3−) and protons (H+). These enzymes impact numerous physiological processes that occur within and across the many compartments in the body. Within compartments, CAs promote rapid H+ buffering and thus the stability of pH-sensitive processes. Between compartments, CAs promote movements of H+, CO2, HCO3−, and related species. This traffic is ...
Source
#1Nobutaka Masuoka (UTokyo: University of Tokyo)H-Index: 4
#2Chitose Yoshimine (UTokyo: University of Tokyo)H-Index: 1
Last. Tatsuhiro Hisatsune (UTokyo: University of Tokyo)H-Index: 27
view all 7 authors...
Background: Oral supplementation of anserine/carnosine helps preserve cognitive functions in healthy older adults. Mild cognitive impairment (MCI) is a transition between cognitive-normal and dementia. Therefore, it needs to investigate whether anserine/carnosine supplementation (ACS) has effects on subjects with MCI. Methods: A randomized, double-blind, placebo-controlled 12-week trial was performed. Fifty-four subjects with MCI were randomized to an active group ingesting 750 mg of anserine an...
Source
#1Martin Schön (Comenius University in Bratislava)H-Index: 11
#2Aya MousaH-Index: 17
Last. Barbora de CourtenH-Index: 42
view all 8 authors...
Neurological, neurodegenerative, and psychiatric disorders represent a serious burden because of their increasing prevalence, risk of disability, and the lack of effective causal/disease-modifying treatments. There is a growing body of evidence indicating potentially favourable effects of carnosine, which is an over-the-counter food supplement, in peripheral tissues. Although most studies to date have focused on the role of carnosine in metabolic and cardiovascular disorders, the physiological p...
Source
#1Joseph John Matthews (NTU: Nottingham Trent University)H-Index: 3
#2Guilherme Giannini Artioli (USP: University of São Paulo)H-Index: 41
Last. Craig Sale (NTU: Nottingham Trent University)H-Index: 36
view all 4 authors...
Carnosine (β-alanyl-L-histidine) plays an important role in exercise performance and skeletal muscle homeostasis. Dietary supplementation with the rate-limiting precursor β-alanine leads to an increase in skeletal muscle carnosine content, which further potentiates its effects. There is significant interest in carnosine and β-alanine across athletic and clinical populations. Traditionally, attention has been given to performance outcomes with less focus on the underlying mechanism(s). Putative p...
Source
#1Eimear Dolan (USP: University of São Paulo)H-Index: 17
#2Bryan Saunders (USP: University of São Paulo)H-Index: 20
Last. Bruno Gualano (USP: University of São Paulo)H-Index: 57
view all 7 authors...
Abstract Histidine containing dipeptides (HCDs: carnosine, anserine and balenine) have numerous therapeutic and ergogenic properties, but there is a lack of consensus on the mechanistic pathways through which they function. Potential roles include intracellular buffering, neutralisation of reactive species, and calcium regulation. Comparative investigations of the HCD content of various species provide unique insight into their most likely mechanisms of action. This review chronologically descri...
Source
#1Marouan Rami (Lille University of Science and Technology)H-Index: 9
#2Jean-Yves Winum (ENSCM: École nationale supérieure de chimie de Montpellier)H-Index: 54
Last. Saïd Yous (Lille University of Science and Technology)H-Index: 18
view all 5 authors...
AbstractUsing histamine as lead molecule, a library of (hetero)aryl substituted thiazol-2,4-yl derivatives incorporating pyridine as proton shuttling moiety were obtained and investigated as activa...
Source
#1Jingjing Zhao (University of Louisville)H-Index: 22
#2Dheeraj Kumar Posa (University of Louisville)H-Index: 2
Last. Shahid P. Baba (University of Louisville)H-Index: 12
view all 10 authors...
Endogenous histidyl dipeptides such as carnosine (β-alanine-l-histidine) form conjugates with lipid peroxidation products such as 4-hydroxy-trans-2-nonenal (HNE and acrolein), chelate metals, and protect against myocardial ischemic injury. Nevertheless, it is unclear whether these peptides protect against cardiac injury by directly reacting with lipid peroxidation products. Hence, to examine whether changes in the structure of carnosine could affect its aldehyde reactivity and metal chelating ab...
Source
#1Murat Bozdag (UniFI: University of Florence)H-Index: 15
#2Abdulmalik Saleh Alfawaz Altamimi (Salman bin Abdulaziz University)H-Index: 5
Last. Fabrizio Carta (UniFI: University of Florence)H-Index: 52
view all 5 authors...
: The current review is intended to highlight recent advances in the search of new and effective modulators of the metalloenzymes Carbonic Anhydrases (CAs, EC 4.2.1.1) expressed in humans (h). CAs reversibly catalyze the CO2 hydration reaction, which is of crucial importance in the regulation of a plethora of fundamental processes at cellular level as well as in complex organisms. The first section of this review will be dedicated to compounds acting as activators of the hCAs (CAAs) and their pr...
Source
#1Ethan J. Anderson (Fraternal Order of Eagles)H-Index: 28
#2Giulio Vistoli (University of Milan)H-Index: 36
Last. Giancarlo AldiniH-Index: 65
view all 15 authors...
: Sugar- and lipid-derived aldehydes are reactive carbonyl species (RCS) frequently used as surrogate markers of oxidative stress in obesity. A pathogenic role for RCS in metabolic diseases of obesity remains controversial, however, partly because of their highly diffuse and broad reactivity and the lack of specific RCS-scavenging therapies. Naturally occurring histidine dipeptides (e.g., anserine and carnosine) show RCS reactivity, but their therapeutic potential in humans is limited by serum c...
Source
#1Andrea Angeli (UniFI: University of Florence)H-Index: 25
#2William A. Donald (UNSW: University of New South Wales)H-Index: 26
Last. Claudiu T. Supuran (UNSW: University of New South Wales)H-Index: 155
view all 4 authors...
Abstract The activation of a β-class carbonic anhydrase (CAs, EC 4.2.1.1) from Leishmania donovani chagasi (LdcCA) was investigated using a panel of natural and non-natural amino acids and amines. The most effective activators belonged to the amine class, with histamine, dopamine, serotonin, 2-pyridyl-methylamine and 4-(2-aminoethyl)-morpholine with activation constants in the range of 0.23–0.94 µM. In addition, 2-(2-aminoethyl)pyridine and 1-(aminoethyl)-piperazine were even more effective acti...
Source
Cited By9
Newest
#1Alessio Nocentini (UniFI: University of Florence)H-Index: 29
#2Doretta Cuffaro (UniPi: University of Pisa)H-Index: 6
Last. Claudiu T. Supuran (UniFI: University of Florence)H-Index: 155
view all 8 authors...
The synthesis and carbonic anhydrase (CA; EC 4.2.1.1) activating effects of a series of oxime ether-based amino alcohols towards four human (h) CA isoforms expressed in human brain, hCA I, II, IV a...
Source
#1Zizhen Zhao (SWU: Southwest University)H-Index: 4
#2Chen FuH-Index: 2
Last. Ailing Fu (SWU: Southwest University)H-Index: 6
view all 4 authors...
Non-alcoholic liver injury (NLI) is a common disease worldwide. Since free radical damage in the liver is a crucial initiator leading to diseases, scavenging excess free radicals has become an essential therapeutic strategy. To enhance the antioxidant capacity of histidine, we synthesized a protonated dimeric histidine, H-bihistidine, and investigated its anti-free radical potential in several free-radical-induced NLI. Results showed that H-bihistidine could strongly scavenge free radicals cause...
Source
#2Rossana IngargiolaH-Index: 4
Last. Giovanna BaronH-Index: 6
view all 13 authors...
Xerostomia, the subjective complaint of dry mouth, is caused by therapeutic interventions or diseases. Nowadays, radiotherapy (RT) in patients with head and neck cancer (HNC) stands out as one of the most important causes of xerostomia. Currently available therapies for the treatment of xerostomia are still less than optimal and xerostomia still represents an unmet clinical need. In this article, we present the results of a prospective clinical study with a new product, AqualiefTM, in patients t...
Source
#1Minna Nortunen (OUH: Oulu University Hospital)H-Index: 1
#2Nina Väkiparta (OUH: Oulu University Hospital)
Last. Tuomo J. Karttunen (OUH: Oulu University Hospital)H-Index: 61
view all 6 authors...
BACKGROUND The pathogenesis of gastroesophageal reflux disease (GERD) has not been resolved in detail. Esophageal epithelial cells provide resistance to acidic reflux via several mechanisms, many of which involve buffering acid with bicarbonate and transporting protons. Carbonic anhydrases (CAs) are enzymes that control the acid-base balance by catalyzing the reversible hydration of carbon dioxide to produce bicarbonate and hydrogen ions. AIMS We aimed to determine the immunohistochemical expres...
Source
#1Giancarlo Aldini (University of Milan)H-Index: 65
#2Barbora de Courten (Monash University)H-Index: 42
Last. Marina Carini (University of Milan)H-Index: 56
view all 10 authors...
Carnosine is an endogenous dipeptide whose oral administration has been found to prevent several oxidative based diseases including lung disease, type 2 diabetes and its micro and macrovascular complications, cardiovascular disorders, neurodegenerative and kidney disease. While it is generally accepted that the beneficial effects of carnosine are due to its antioxidant, anti-advanced glycation end product (AGE) and -advanced lipoxidation end product (ALE) and anti-inflammatory properties, the mo...
Source
#1Claudiu T. Supuran (UniFI: University of Florence)H-Index: 155
Source
Coumarins constitute a relatively new class of inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), possessing a unique inhibition mechanism, acting as “prodrug inhibitors.” They unde...
Source
#1Niccolò Chiaramonte (UniFI: University of Florence)H-Index: 6
#2Soumia Maach (UniFI: University of Florence)H-Index: 1
Last. Maria Novella Romanelli (UniFI: University of Florence)H-Index: 24
view all 10 authors...
The Carbonic Anhydrase (CA, EC 4.2.1.1) activating properties of histamine have been known for a long time. This compound has been extensively modified but only in few instances the imidazole ring ...
Source
#1Claudiu T. Supuran (UniFI: University of Florence)H-Index: 155
ABSTRACTIntroduction: The spacious active site cavity of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) shows a great versatility for a variety of binding modes for modulators of activity, i...
Source
This website uses cookies.
We use cookies to improve your online experience. By continuing to use our website we assume you agree to the placement of these cookies.
To learn more, you can find in our Privacy Policy.