A Mechanistic Kinetic Description of Lactate Dehydrogenase Elucidating Cancer Diagnosis and Inhibitor Evaluation

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2017 Jan 25

PMID 28114833

Citations 4

Authors

Peifeng Tang

Jianlin Xu

Christopher L Oliveira

Zheng Jian Li

Shijie Liu

Affiliations

Soon will be listed here.

Abstract

As a key enzyme for glycolysis, lactate dehydrogenase (LDH) remains as a topic of great interest in cancer study. Though a number of kinetic models have been applied to describe the dynamic behavior of LDH, few can reflect its actual mechanism, making it difficult to explain the observed substrate and competitor inhibitions at wide concentration ranges. A novel mechanistic kinetic model is developed based on the enzymatic processes and the interactive properties of LDH. Better kinetic simulation as well as new enzyme interactivity information and kinetic properties extracted from published articles via the novel model was presented. Case studies were presented to a comprehensive understanding of the effect of temperature, substrate, and inhibitor on LDH kinetic activities for promising application in cancer diagnosis, inhibitor evaluation, and adequate drug dosage prediction.

Citing Articles

Preparation of a Mesoporous Biosensor for Human Lactate Dehydrogenase for Potential Anticancer Inhibitor Screening.

Cocuzza C, Antoniono E, Ottone C, Cauda V, Fino D, Piumetti M ACS Biomater Sci Eng. 2023; 9(11):6045-6057.

PMID: 37856794 PMC: 10646870. DOI: 10.1021/acsbiomaterials.3c00582.

Signal-enhanced real-time magnetic resonance of enzymatic reactions at millitesla fields.

Korchak S, Jagtap A, Gloggler S Chem Sci. 2021; 12(1):314-319.

PMID: 34163599 PMC: 8178804. DOI: 10.1039/d0sc04884d.

Serum and salivary levels of lactate dehydrogenase in oral squamous cell carcinoma, oral lichen planus and oral lichenoid reaction.

Gholizadeh N, Ramandi M, Motiee-Langroudi M, Jafari M, Sharouny H, Sheykhbahaei N BMC Oral Health. 2020; 20(1):314.

PMID: 33167957 PMC: 7653894. DOI: 10.1186/s12903-020-01306-0.

Systematic development of temperature shift strategies for Chinese hamster ovary cells based on short duration cultures and kinetic modeling.

Xu J, Tang P, Yongky A, Drew B, Borys M, Liu S MAbs. 2018; 11(1):191-204.

PMID: 30230966 PMC: 6343780. DOI: 10.1080/19420862.2018.1525262.

References

Levitzki A . The refolding of lactate dehydrogenase subunits and their assembly to the functional tetramer. Biochim Biophys Acta. 1976; 445(2):261-79. DOI: 10.1016/0005-2744(76)90081-4. View

Huang C, Kuo W, Huang Y, Lee T, Yu L . Resistance to hypoxia-induced necroptosis is conferred by glycolytic pyruvate scavenging of mitochondrial superoxide in colorectal cancer cells. Cell Death Dis. 2013; 4:e622. PMC: 3674358. DOI: 10.1038/cddis.2013.149. View

Serganova I, Rizwan A, Ni X, Thakur S, Vider J, Russell J . Metabolic imaging: a link between lactate dehydrogenase A, lactate, and tumor phenotype. Clin Cancer Res. 2011; 17(19):6250-6261. PMC: 4217119. DOI: 10.1158/1078-0432.CCR-11-0397. View

Cornish-Bowden A . Introduction: Enzyme catalysis and allostery: a century of advances in molecular understanding. FEBS J. 2014; 281(2):433-4. DOI: 10.1111/febs.12695. View

Deng H, Brewer S, Vu D, Clinch K, Callender R, Dyer R . On the pathway of forming enzymatically productive ligand-protein complexes in lactate dehydrogenase. Biophys J. 2008; 95(2):804-13. PMC: 2440432. DOI: 10.1529/biophysj.108.128884. View

GUBERNIEVA L, Safronova E, Malakhov V . [Study of some kinetic properties of human lactate dehydrogenase isoenzymes]. Biokhimiia. 1974; 39(6):1241-5. View

Dragowska W, Ginj M, Kozlowski P, Yung A, Ruth T, Adam M . Overexpression of HER-2 in MDA-MB-435/LCC6 Tumours is Associated with Higher Metabolic Activity and Lower Energy Stress. Sci Rep. 2016; 6:18537. PMC: 4698760. DOI: 10.1038/srep18537. View

Koppenol W, Bounds P, Dang C . Otto Warburg's contributions to current concepts of cancer metabolism. Nat Rev Cancer. 2011; 11(5):325-37. DOI: 10.1038/nrc3038. View

Talaiezadeh A, Shahriari A, Tabandeh M, Fathizadeh P, Mansouri S . Kinetic characterization of lactate dehydrogenase in normal and malignant human breast tissues. Cancer Cell Int. 2015; 15:19. PMC: 4334850. DOI: 10.1186/s12935-015-0171-7. View

10.

Cook W, Senkovich O, Hernandez A, Speed H, Chattopadhyay D . Biochemical and structural characterization of Cryptosporidium parvum Lactate dehydrogenase. Int J Biol Macromol. 2014; 74:608-19. DOI: 10.1016/j.ijbiomac.2014.12.019. View

11.

Rodriguez-Paez L, Chena-Taboada M, Cabrera-Hernandez A, Cordero-Martinez J, Wong C . Oxamic acid analogues as LDH-C4-specific competitive inhibitors. J Enzyme Inhib Med Chem. 2011; 26(4):579-86. DOI: 10.3109/14756366.2011.566221. View

12.

Schmid G, Blanch H . Extra- and intracellular metabolite concentrations for murine hybridoma cells. Appl Microbiol Biotechnol. 1992; 36(5):621-5. DOI: 10.1007/BF00183239. View

13.

Shi Y, Pinto B . Human lactate dehydrogenase a inhibitors: a molecular dynamics investigation. PLoS One. 2014; 9(1):e86365. PMC: 3895040. DOI: 10.1371/journal.pone.0086365. View

14.

Fiume L, Manerba M, Vettraino M, Di Stefano G . Inhibition of lactate dehydrogenase activity as an approach to cancer therapy. Future Med Chem. 2014; 6(4):429-45. DOI: 10.4155/fmc.13.206. View

15.

MONOD J, Changeux J, Jacob F . Allosteric proteins and cellular control systems. J Mol Biol. 1963; 6:306-29. DOI: 10.1016/s0022-2836(63)80091-1. View

16.

Rani R, Kumar V . Recent Update on Human Lactate Dehydrogenase Enzyme 5 (hLDH5) Inhibitors: A Promising Approach for Cancer Chemotherapy. J Med Chem. 2015; 59(2):487-96. DOI: 10.1021/acs.jmedchem.5b00168. View

17.

Nicholls D, Wood I, Nobbs T, Clarke A, HOLBROOK J, Atkinson T . Dissecting the contributions of a specific side-chain interaction to folding and catalysis of Bacillus stearothermophilus lactate dehydrogenase. Eur J Biochem. 1993; 212(2):447-55. DOI: 10.1111/j.1432-1033.1993.tb17681.x. View

18.

Eggert M, Byrne M, Chambers R . Impact of high pyruvate concentration on kinetics of rabbit muscle lactate dehydrogenase. Appl Biochem Biotechnol. 2011; 165(2):676-86. DOI: 10.1007/s12010-011-9287-y. View

19.

Matoba Y, Miyasako M, Matsuo K, Oda K, Noda M, Higashikawa F . An alternative allosteric regulation mechanism of an acidophilic l-lactate dehydrogenase from Enterococcus mundtii 15-1A. FEBS Open Bio. 2014; 4:834-47. PMC: 4219987. DOI: 10.1016/j.fob.2014.08.006. View

20.

Najdi T, Yang C, Shapiro B, Hatfield G, Mjolsness E . Application of a generalized MWC model for the mathematical simulation of metabolic pathways regulated by allosteric enzymes. J Bioinform Comput Biol. 2006; 4(2):335-55. DOI: 10.1142/s0219720006001862. View