دورية أكاديمية
أعرض في EDS

Modeling the distribution of enzymes on lipid vesicles: A novel framework for surface-mediated reactions in coagulation.

التفاصيل البيبلوغرافية
العنوان: Modeling the distribution of enzymes on lipid vesicles: A novel framework for surface-mediated reactions in coagulation.
المؤلفون: Madrigal J; Mathematics Department, University of North Carolina at Chapel Hill, Chapel Hill, 27599-3250, NC, USA., Monroe DM; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Sindi SS; Mathematics Department, University of California Merced, Merced, CA, USA., Leiderman K; Mathematics Department, University of North Carolina at Chapel Hill, Chapel Hill, 27599-3250, NC, USA; UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Computational Medicine Program, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: karin.leiderman@unc.edu.
المصدر: Mathematical biosciences [Math Biosci] 2024 Aug; Vol. 374, pp. 109229. Date of Electronic Publication: 2024 Jun 06.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Elsevier Country of Publication: United States NLM ID: 0103146 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3134 (Electronic) Linking ISSN: 00255564 NLM ISO Abbreviation: Math Biosci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, American Elsevier.
مواضيع طبية MeSH: Blood Coagulation*/physiology , Factor VIIa*/metabolism, Models, Biological ; Humans ; Kinetics ; Lipids ; Thromboplastin/metabolism
مستخلص: Blood coagulation is a network of biochemical reactions wherein dozens of proteins act collectively to initiate a rapid clotting response. Coagulation reactions are lipid-surface dependent, and this dependence is thought to help localize coagulation to the site of injury and enhance the association between reactants. Current mathematical models of coagulation either do not consider lipid as a variable or do not agree with experiments where lipid concentrations were varied. Since there is no analytic rate law that depends on lipid, only apparent rate constants can be derived from enzyme kinetic experiments. We developed a new mathematical framework for modeling enzymes reactions in the presence of lipid vesicles. Here the concentrations are such that only a fraction of the vesicles harbor bound enzymes and the rest remain empty. We call the lipid vesicles with and without enzyme TF:VIIa + and TF:VIIa - lipid, respectively. Since substrate binds to both TF:VIIa + and TF:VIIa - lipid, our model shows that excess empty lipid acts as a strong sink for substrate. We used our framework to derive an analytic rate equation and performed constrained optimization to estimate a single, global set of intrinsic rates for the enzyme-substrate pair. Results agree with experiments and reveal a critical lipid concentration where the conversion rate of the substrate is maximized, a phenomenon known as the template effect. Next, we included product inhibition of the enzyme and derived the corresponding rate equations, which enables kinetic studies of more complex reactions. Our combined experimental and mathematical study provides a general framework for uncovering the mechanisms by which lipid mediated reactions impact coagulation processes.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
References: Biochim Biophys Acta. 1998 Nov 10;1376(3):433-53. (PMID: 9805008)
J Biol Chem. 1992 Dec 25;267(36):26110-20. (PMID: 1464622)
Acc Chem Res. 2017 Dec 19;50(12):2949-2957. (PMID: 29131941)
J Biol Chem. 1984 Feb 10;259(3):1447-53. (PMID: 6693415)
Anal Biochem. 2019 Sep 1;580:62-71. (PMID: 31091429)
Biochem J. 1990 Jan 15;265(2):327-36. (PMID: 2302175)
Biochemistry. 1989 Sep 5;28(18):7453-61. (PMID: 2819080)
J Biol Chem. 1988 Mar 15;263(8):3823-34. (PMID: 3346225)
J Biol Chem. 1977 Dec 10;252(23):8481-8. (PMID: 925006)
Biochemistry. 2005 Jun 7;44(22):8187-97. (PMID: 15924438)
Biochemistry. 2007 May 22;46(20):6134-40. (PMID: 17469850)
Eur J Biochem. 1982 Feb;122(2):429-36. (PMID: 7060583)
Int J Numer Method Biomed Eng. 2023 Nov;39(11):e3689. (PMID: 36802118)
Biochim Biophys Acta. 1986 Jun 13;858(1):161-8. (PMID: 3707960)
Blood Cells Mol Dis. 2006 Mar-Apr;36(2):194-8. (PMID: 16529959)
J Biol Chem. 1982 Jul 10;257(13):7360-5. (PMID: 7085630)
Proc Natl Acad Sci U S A. 2021 Nov 23;118(47):. (PMID: 34789575)
J Biol Chem. 1980 Jan 10;255(1):274-83. (PMID: 7350159)
J Thromb Thrombolysis. 2003 Aug-Oct;16(1-2):17-20. (PMID: 14760207)
J Biol Chem. 2004 Apr 23;279(17):17241-9. (PMID: 14963035)
Phys Biol. 2015 Mar 06;12(2):026003. (PMID: 25743228)
Adv Exp Med Biol. 1985;192:359-71. (PMID: 3914834)
Chem Phys Lipids. 1994 Sep 6;73(1-2):209-22. (PMID: 8001182)
Biochemistry. 1983 May 10;22(10):2427-32. (PMID: 6860639)
J Biol Chem. 1995 Aug 11;270(32):18711-4. (PMID: 7642515)
J Biol Chem. 1992 Nov 25;267(33):23696-706. (PMID: 1429710)
Angew Chem Int Ed Engl. 2017 Mar 20;56(13):3718-3722. (PMID: 28199769)
Biochemistry. 1986 Jul 15;25(14):4020-33. (PMID: 3091068)
معلومات مُعتمدة: R01 HL120728 United States HL NHLBI NIH HHS; R01 HL151984 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: Blood coagulation; Enzyme kinetics; Lipid vesicles; Mathematical modeling; Product inhibition
المشرفين على المادة: EC 3.4.21.21 (Factor VIIa)
0 (Lipids)
9035-58-9 (Thromboplastin)
تواريخ الأحداث: Date Created: 20240608 Date Completed: 20240714 Latest Revision: 20240718
رمز التحديث: 20240718
مُعرف محوري في PubMed: PMC11250983
DOI: 10.1016/j.mbs.2024.109229
PMID: 38851530
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-3134
DOI:10.1016/j.mbs.2024.109229