Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Esterases in the Circulatory System: Structure, Function, Activity Modulation and Involvement in Pathology

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 19531

Share This Special Issue

Special Issue Editor

Prof. Dr. Marc A. Ilies

E-Mail Website
Guest Editor

Department of Pharmaceutical Sciences and Moulder Center of Drug Discovery Research, Temple University School of Pharmacy, Philadelphia, PA, USA
Interests: medicinal chemistry; chemical biology; drug and nucleic acid delivery systems
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The circulatory system contains a plethora of esterases, which are enzymes specialized in cleaving various esters that are normally and recurrently present in circulation as part of the body homeostasis or that can appear transiently due to diet, various dysfunction or diseases. Due to the large range of lipophilicity of the substrates that can be normally or potentially present in the bloodstream, the circulatory system displays a wide range of esterases, either solubilized in blood/plasma, attached on the blood vessel walls and/or encapsulated into various cells present in the bloodstream (red blood cells, platelets, leukocytes, etc.). The proposed thematic issue aims to detail their structure and mechanism of action as a function of the lipophilicity of the esters processed and their physiologic role(s) in the circulatory system. Special emphasis will be placed on the involvement of different circulatory system esterases in diseases and their activity modulation (inhibition/activation) for therapeutic purposes.

Prof. Dr. Marc A. Ilies
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

esterases and lipases
circulatory system
blood, plasma, blood vessels, figurative elements of blood
physiopathology
structure and catalysis mechanism
substrate selectivity
activity assays
inhibition and activation
drugs in clinical use and under development

Published Papers (5 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

13 pages, 4305 KiB

Open AccessArticle

Rational Design of Lipase ROL to Increase Its Thermostability for Production of Structured Tags

by Jeng Yeong Chow and Giang Kien Truc Nguyen

Int. J. Mol. Sci. 2022, 23(17), 9515; https://doi.org/10.3390/ijms23179515 - 23 Aug 2022

Cited by 10 | Viewed by 1859

Abstract

1,3-regiospecific lipases are important enzymes that are heavily utilized in the food industries to produce structured triacylglycerols (TAGs). The Rhizopus oryzae lipase (ROL) has recently gained interest because this enzyme possesses high selectivity and catalytic efficiency. However, its low thermostability limits its use towards reactions that work at lower temperature. Most importantly, the enzyme cannot be used for the production of 1,3-dioleoyl-2-palmitoylglycerol (OPO) and 1,3-stearoyl-2-oleoyl-glycerol (SOS) due to the high melting points of the substrates used for the reaction. Despite various engineering efforts used to improve the thermostability of ROL, the enzyme is unable to function at temperatures above 60 °C. Here, we describe the rational design of ROL to identify variants that can retain their activity at temperatures higher than 60 °C. After two rounds of mutagenesis and screening, we were able to identify a mutant ROL_10x that can retain most of its activity at 70 °C. We further demonstrated that this mutant is useful for the synthesis of SOS while minimal product formation was observed with ROL_WT. Our engineered enzyme provides a promising solution for the industrial synthesis of structured lipids at high temperature. Full article

(This article belongs to the Special Issue Esterases in the Circulatory System: Structure, Function, Activity Modulation and Involvement in Pathology)

► Show Figures

Figure 1

14 pages, 1610 KiB

Open AccessArticle

Evaluation of the Impact of Esterases and Lipases from the Circulatory System against Substrates of Different Lipophilicity

by Leslie Lam and Marc A. Ilies

Int. J. Mol. Sci. 2022, 23(3), 1262; https://doi.org/10.3390/ijms23031262 - 23 Jan 2022

Cited by 8 | Viewed by 3581

Abstract

Esterases and lipases can process amphiphilic esters used as drugs and prodrugs and impact their pharmacokinetics and biodistribution. These hydrolases can also process ester components of drug delivery systems (DDSs), thus triggering DDSs destabilization with premature cargo release. In this study we tested and optimized assays that allowed us to quantify and compare individual esterase contributions to the degradation of substrates of increased lipophilicity and to establish limitations in terms of substrates that can be processed by a specific esterase/lipase. We have studied the impact of carbonic anhydrase; phospholipases A1, A2, C and D; lipoprotein lipase; and standard lipase on the hydrolysis of 4-nitrophenyl acetate, 4-nitrophenyl palmitate, DGGR and POPC liposomes, drawing structure–property relationships. We found that the enzymatic activity of these proteins was highly dependent on the lipophilicity of the substrate used to assess them, as expected. The activity observed for classical esterases was diminished when lipophilicity of the substrate increased, while activity observed for lipases generally increased, following the interfacial activation model, and was highly dependent on the type of lipase and its structure. The assays developed allowed us to determine the most sensitive methods for quantifying enzymatic activity against substrates of particular types and lipophilicity. Full article

(This article belongs to the Special Issue Esterases in the Circulatory System: Structure, Function, Activity Modulation and Involvement in Pathology)

► Show Figures

Figure 1

22 pages, 11981 KiB

Open AccessArticle

Esterase Activity of Serum Albumin Studied by ¹H NMR Spectroscopy and Molecular Modelling

by Daria A. Belinskaia, Polina A. Voronina, Mikhail A. Vovk, Vladimir I. Shmurak, Anastasia A. Batalova, Richard O. Jenkins and Nikolay V. Goncharov

Int. J. Mol. Sci. 2021, 22(19), 10593; https://doi.org/10.3390/ijms221910593 - 30 Sep 2021

Cited by 8 | Viewed by 2409

Abstract

Serum albumin possesses esterase and pseudo-esterase activities towards a number of endogenous and exogenous substrates, but the mechanism of interaction of various esters and other compounds with albumin is still unclear. In the present study, proton nuclear magnetic resonance (¹H NMR) has been applied to the study of true esterase activity of albumin, using the example of bovine serum albumin (BSA) and p-nitrophenyl acetate (NPA). The site of BSA esterase activity was then determined using molecular modelling methods. According to the data obtained, the accumulation of acetate in the presence of BSA in the reaction mixture is much more intense as compared with the spontaneous hydrolysis of NPA, which indicates true esterase activity of albumin towards NPA. Similar results were obtained for p-nitophenyl propionate (NPP) as substrate. The rate of acetate and propionate release confirms the assumption that there is a site of true esterase activity in the albumin molecule, which is different from the site of the pseudo-esterase activity Sudlow II. The results of molecular modelling of BSA and NPA interaction make it possible to postulate that Sudlow site I is the site of true esterase activity of albumin. Full article

(This article belongs to the Special Issue Esterases in the Circulatory System: Structure, Function, Activity Modulation and Involvement in Pathology)

► Show Figures

Figure 1

15 pages, 2841 KiB

Open AccessArticle

A Novel Lipase from Lasiodiplodia theobromae Efficiently Hydrolyses C8-C10 Methyl Esters for the Preparation of Medium-Chain Triglycerides’ Precursors

by Andre Mong Jie Ng, Renliang Yang, Hongfang Zhang, Bo Xue, Wen Shan Yew and Giang Kien Truc Nguyen

Int. J. Mol. Sci. 2021, 22(19), 10339; https://doi.org/10.3390/ijms221910339 - 25 Sep 2021

Cited by 3 | Viewed by 3254

Abstract

Medium-chain triglycerides (MCTs) are an emerging choice to treat neurodegenerative disorders such as Alzheimer’s disease. They are triesters of glycerol and three medium-chain fatty acids, such as capric (C8) and caprylic (C10) acids. The availability of C8–C10 methyl esters (C8–C10 ME) from vegetable oil processes has presented an opportunity to use methyl esters as raw materials for the synthesis of MCTs. However, there are few reports on enzymes that can efficiently hydrolyse C8–C10 ME to industrial specifications. Here, we report the discovery and identification of a novel lipase from Lasiodiplodia theobromae fungus (LTL1), which hydrolyses C8–C10 ME efficiently. LTL1 can perform hydrolysis over pH ranges from 3.0 to 9.0 and maintain thermotolerance up to 70 °C. It has high selectivity for monoesters over triesters and displays higher activity over commercially available lipases for C8–C10 ME to achieve 96.17% hydrolysis within 31 h. Structural analysis by protein X-ray crystallography revealed LTL1’s well-conserved lipase core domain, together with a partially resolved N-terminal subdomain and an inserted loop, which may suggest its hydrolytic preference for monoesters. In conclusion, our results suggest that LTL1 provides a tractable route towards to production of C8–C10 fatty acids from methyl esters for the synthesis of MCTs. Full article

(This article belongs to the Special Issue Esterases in the Circulatory System: Structure, Function, Activity Modulation and Involvement in Pathology)

► Show Figures

Graphical abstract

Review

Jump to: Research

37 pages, 3103 KiB

Open AccessReview

Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties

by Daria A. Belinskaia, Polina A. Voronina, Vladimir I. Shmurak, Richard O. Jenkins and Nikolay V. Goncharov

Int. J. Mol. Sci. 2021, 22(19), 10318; https://doi.org/10.3390/ijms221910318 - 25 Sep 2021

Cited by 110 | Viewed by 7256

Abstract

Being one of the main proteins in the human body and many animal species, albumin plays a decisive role in the transport of various ions—electrically neutral and charged molecules—and in maintaining the colloidal osmotic pressure of the blood. Albumin is able to bind to almost all known drugs, as well as many nutraceuticals and toxic substances, largely determining their pharmaco- and toxicokinetics. Albumin of humans and respective representatives in cattle and rodents have their own structural features that determine species differences in functional properties. However, albumin is not only passive, but also an active participant of pharmacokinetic and toxicokinetic processes, possessing a number of enzymatic activities. Numerous experiments have shown esterase or pseudoesterase activity of albumin towards a number of endogeneous and exogeneous esters. Due to the free thiol group of Cys34, albumin can serve as a trap for reactive oxygen and nitrogen species, thus participating in redox processes. Glycated albumin makes a significant contribution to the pathogenesis of diabetes and other diseases. The interaction of albumin with blood cells, blood vessels and tissue cells outside the vascular bed is of great importance. Interactions with endothelial glycocalyx and vascular endothelial cells largely determine the integrative role of albumin. This review considers the esterase, antioxidant, transporting and signaling properties of albumin, as well as its structural and functional modifications and their significance in the pathogenesis of certain diseases. Full article

(This article belongs to the Special Issue Esterases in the Circulatory System: Structure, Function, Activity Modulation and Involvement in Pathology)

► Show Figures

Journal Menu

Journal Browser

Esterases in the Circulatory System: Structure, Function, Activity Modulation and Involvement in Pathology

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (5 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI