{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:08:16Z","timestamp":1791655696364,"version":"4.3.4"},"reference-count":62,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Betanin (Bet), a natural compound, exhibits potent antioxidant and metabolic regulatory properties, yet its effect on cellular glucose utilization remains unclear. This study investigated, for the first time, the impact of Bet on glucose consumption and the activation of key carbohydrate\u2013catabolic pathways in human erythrocytes. Methods: In vitro assays were performed to evaluate enzyme inhibition and activation. Human erythrocytes were incubated with Bet to assess glucose consumption. Enzyme activities were measured spectrophotometrically, and molecular docking was used to analyze binding interactions. Results: Our results demonstrate that Bet inhibits digestive enzymes in a dose-dependent manner, with maximal inhibition at 90 \u00b5g\/mL for pancreatic lipase and 70 \u00b5g\/mL for \u03b1-amylase, showing IC50 values of 48.8 and 31.9 \u00b5g\/mL, respectively, supported by strong binding affinities of \u22129.3 and \u22128.9 Kcal\/mol. These interactions are stronger than those of orlistat (\u22126.9 Kcal\/mol) and acarbose (\u22127.7 Kcal\/mol). Bet also induced the activity of AMPK with an IC50 of 1.83 \u00b5g\/mL and a BE of \u22127.90 Kcal\/mol, compared to the specific AMPK activator A-769662, which had an IC50 of 1.29 \u00b5g\/mL and a binding energy of \u221210.0 Kcal\/mol. Consequently, Bet stimulated key glycolytic enzymes, reaching maximal activation (~62%) at 1.4 \u00b5g\/mL for hexokinase (HK) and glucose-6-phosphate dehydrogenase (G6PD), and at 1.6 \u00b5g\/mL for pyruvate kinase (PK), supported by binding energies of \u22127.2, \u22127.5, and \u22129.0 Kcal\/mol and AC50 values of 0.87, 0.98, and 0.91 \u00b5g\/mL, respectively. Moreover, Bet enhanced key Krebs cycle enzymes (IDH, SDH, MDH, LDH) in a dose-dependent manner, with AC50 values of 0.76, 0.80, 0.72, and 0.52 \u00b5g\/mL and strong binding energies (\u22127.8, \u22127.8, and \u22128.4 Kcal\/mol), reaching maximal activation near 1.4 \u00b5g\/mL. Bet also increased glucose consumption by human erythrocytes. Conclusions: Bet enhances glucose utilization by inhibiting digestive enzymes and activating intracellular metabolic pathways, suggest potential metabolic regulatory effects.<\/jats:p>","DOI":"10.3390\/ph19060947","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:49:42Z","timestamp":1781743782000},"page":"947","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of Betanin on Key Enzymes Related to Obesity, Diabetes, Insulin Signaling Pathway, and Metabolic Disorders: In Vitro, Cellular, and In Silico Study"],"prefix":"10.3390","volume":"19","author":[{"given":"Faiza I. A.","family":"Abdella","sequence":"first","affiliation":[{"name":"Department of Chemistry, College of Science, University of Ha\u2019il, Ha\u2019il 81451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalal","family":"Alardan","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, University of Ha\u2019il, Ha\u2019il 81451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nawal S.","family":"Alshammari","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, University of Ha\u2019il, Ha\u2019il 81451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahlam Abdulrahman","family":"Alrashdi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Science, University of Ha\u2019il, Ha\u2019il 81451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mourad","family":"Jridi","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Physiology and Valorization of Bio-Resources (LR23ES08), Higher Institute of Biotechnology of Beja (ISBB), University of Jendouba, Beja 9000, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4706-5181","authenticated-orcid":false,"given":"Sarra","family":"Boudriga","sequence":"additional","affiliation":[{"name":"Laboratory of Heterocyclic Chemistry Natural Product and Reactivity (LR11ES39), Department of Chemistry, Faculty of Science of Monastir, University of Monastir, Monastir 5019, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4295-1378","authenticated-orcid":false,"given":"Khaled","family":"Hamden","sequence":"additional","affiliation":[{"name":"Laboratory of Bioresources: Integrative Biology and Exploiting, Higher Institute of Biotechnology of Monastir, University of Monastir, Monastir 5000, Tunisia"},{"name":"Higher School of Health Sciences and Technology of Sfax, Sfax University, Sfax 3000, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102882","DOI":"10.1016\/j.pmedr.2024.102882","article-title":"The Global Burden of Overweight-Obesity and Its Association with Economic Status, Benefiting from STEPs Survey of WHO Member States: A Meta-Analysis","volume":"46","author":"Islam","year":"2024","journal-title":"Prev. Med. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lin, X., and Li, H. (2021). Obesity: Epidemiology, Pathophysiology, and Therapeutics. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.706978"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Huang, Q., Li, Y., Yu, M., Lv, Z., Lu, F., Xu, N., Zhang, Q., Shen, J., Zhu, J., and Jiang, H. (2025). Global Burden and Risk Factors of Type 2 Diabetes Mellitus from 1990 to 2021, with Forecasts to 2050. Front. Endocrinol., 16.","DOI":"10.3389\/fendo.2025.1538143"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/1477-7525-12-100","article-title":"Abdominal Obesity and Its Association with Health-Related Quality of Life in Adults: A Population-Based Study in Five Chinese Cities","volume":"12","author":"Wu","year":"2014","journal-title":"Health Qual. Life Outcomes"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"103181","DOI":"10.1016\/j.dsx.2024.103181","article-title":"Decoding the Disproportionate Risk Factor Landscape of Global Type 2 Diabetes Burden in Adults: An Attribution Analysis from 1990 to 2050","volume":"19","author":"Huang","year":"2025","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"155808","DOI":"10.1016\/j.prp.2024.155808","article-title":"Seabuckthorn Polysaccharide Alleviates Renal Fibrosis in a Mouse Model of Diabetic Nephropathy via P311\/TGF\u03b21\/Fstl1 Signaling Pathway","volume":"267","author":"Huang","year":"2025","journal-title":"Pathol. Res. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.sajb.2018.04.001","article-title":"Screening the in Vitro Antioxidant, Antimicrobial, Anticholinesterase, Antidiabetic Activities of Endemic Achillea Cucullata (Asteraceae) Ethanol Extract","volume":"120","author":"Eruygur","year":"2019","journal-title":"S. Afr. J. Bot."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.sajb.2022.10.048","article-title":"Comprehensive Metabolic Profiling of Acantholimon Caryophyllaceum Using LC\u2013HRMS and Evaluation of Antioxidant Activities, Enzyme Inhibition Properties and Molecular Docking Studies","volume":"151","author":"Kiziltas","year":"2022","journal-title":"S. Afr. J. Bot."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/j.tem.2024.12.006","article-title":"The Growing Range of Complications of Diabetes Mellitus","volume":"36","author":"Hamblin","year":"2025","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.diabet.2010.11.002","article-title":"Metformin and Digestive Disorders","volume":"37","author":"Bouchoucha","year":"2011","journal-title":"Diabetes Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"8050374","DOI":"10.1155\/jdr\/8050374","article-title":"Protective Effects of Isolated Curcumin From Curcuma Longa on Key Enzymes Involved in the Insulin Signaling Pathway and Digestive and Metabolic Enzymes Associated with Obesity, Type 2 Diabetes, and Hypertension","volume":"2025","author":"Alhar","year":"2025","journal-title":"J. Diabetes Res."},{"key":"ref_12","first-page":"1","article-title":"Influence of the Extraction Method of Curcuminoids on the Antidiabetic and Antioxidant Properties and Cytotoxicity in Normal and Cancer Cells","volume":"20","author":"Saad","year":"2026","journal-title":"J. Food Meas. Charact."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"110639","DOI":"10.1016\/j.enzmictec.2025.110639","article-title":"Prodigiosin as N-Heterocyclic Compound: Production Optimization, Bioactivity Evaluation, and In-Silico Docking Against Key Enzymes Related to Inflammation, Obesity, Diabetes, and the Insulin Signaling Pathway","volume":"188","author":"Alanezi","year":"2025","journal-title":"Enzym. Microb. Technol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"106569","DOI":"10.1016\/j.fbio.2025.106569","article-title":"Heterocyclic Betanin from Opuntia stricta Var. Dillenii: Purification, Stability, and Effects on Carbohydrate Digestion, Absorption, Metabolism, and Enzyme Inhibition in Obese Rats with Type 2 Diabetes","volume":"68","author":"Alshammari","year":"2025","journal-title":"Food Biosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"118277","DOI":"10.1016\/j.biopha.2025.118277","article-title":"Parietin from Lichen: Extraction, Characterization, and in Silico, in Vitro, and in Vivo Evaluation of Its Protective Effects against Inflammation, Oxidative Stress, and Neutrophil Infiltration in Diabetic Rat Tissues","volume":"189","author":"Abdella","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_16","first-page":"1","article-title":"C-Phycocyanin Protects against Obesity-Associated Type 2 Diabetes-Induced Male Fertility Dysfunction via Key Enzyme Regulation","volume":"28","author":"AlRashidi","year":"2026","journal-title":"Asian J. Androl."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"El-Sofany, W.I., Alshammari, A.F., Alshammari, M.Z., Alshammari, H.K., Alshammari, N.S., Masood, N., and Hamden, K. (2026). Extraction, Characterization, and Biological Evaluation of Atranorin Against Diabetes-Induced Reproductive Dysfunction Through Modulation of Oxidative Stress, Inflammatory Pathways and Key Reproductive Enzymes. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27052416"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.sajb.2023.03.013","article-title":"The Ethyl Acetate Extract from Abutilon Fruticosum Guill and Perr. as a Potential Diabetes\u2013Cancer Prophylactic: A Cytotoxic, \u03b1-Glucosidase, and in-Silico Study","volume":"156","author":"Gouda","year":"2023","journal-title":"S. Afr. J. Bot."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.sajb.2025.06.037","article-title":"HPLC-DAD Profiling, Antioxidant, Anticholinesterase, and Antidiabetic Activities of Four Algerian Edible Plant Extracts: An in Vitro and in Silico Study","volume":"184","author":"Siga","year":"2025","journal-title":"S. Afr. J. Bot."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.sajb.2025.09.051","article-title":"The Hypoglycemic and Antioxidant Potential of the Methanolic Extract from Eucomis autumnalis (Mill.) Chitt Leaves: An in Vitro and in Silico Investigation","volume":"187","author":"Oyedemi","year":"2025","journal-title":"S. Afr. J. Bot."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.sajb.2025.10.048","article-title":"Preparation of Cannabinoid Extracts from Hemp and Their Hypoglycemic Effects","volume":"187","author":"Sun","year":"2025","journal-title":"S. Afr. J. Bot."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.sajb.2025.01.040","article-title":"Hesperetin-Supplemented Soybean and Ginger Hydroalcoholic Extracts Alleviate Diabetic Cardiomyopathy in Streptozotocin Induced Diabetic Rats by Modulating NF-\u039aB\/MMP-9\/TIMPs Pathway","volume":"179","author":"Ritu","year":"2025","journal-title":"S. Afr. J. Bot."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.sajb.2015.02.016","article-title":"Analyses and Profiling of Extract and Fractions of Neglected Weed Mimosa Pudica Linn. Traditionally Used in Southeast Asia to Treat Diabetes","volume":"99","author":"Tunna","year":"2015","journal-title":"S. Afr. J. Bot."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.sajb.2024.09.062","article-title":"Investigating the Hepatoprotective and Antidiabetic Properties of Cryogenically Pulverized Turkish Propolis Water Extracts in Streptozotocin-Induced Diabetic Rats","volume":"174","author":"Omer","year":"2024","journal-title":"S. Afr. J. Bot."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9522830","DOI":"10.1155\/2023\/9522830","article-title":"Betalain-Enriched Beetroots Exhibit Antiulcer and Anti-Inflammatory Potentials","volume":"2023","author":"Saad","year":"2023","journal-title":"J. Food Process. Preserv."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"28313","DOI":"10.1039\/D5RA03339J","article-title":"Maturation-Stage Effects of Ziziphus Spina-Christi Fruits and Leaves on Digestive, Inflammatory, Antioxidant, and Glucose Metabolism Enzymes in Obese Rats with Type 2 Diabetes","volume":"15","author":"Alshammari","year":"2025","journal-title":"RSC Adv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"102644","DOI":"10.1016\/j.rechem.2025.102644","article-title":"Isolation, Characterization, and Gastroprotective Effects of Lycopene against Key Enzymes Involved in Acidity Activation, Inflammation, and Oxidative Stress in Ethanol-Induced Gastric Ulcer in Rats","volume":"17","author":"Bahrini","year":"2025","journal-title":"Results Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2751","DOI":"10.1021\/bi00009a003","article-title":"The 2.46 .ANG. Resolution Structure of the Pancreatic Lipase-Colipase Complex Inhibited by a C11 Alkyl Phosphonate","volume":"34","author":"Egloff","year":"1995","journal-title":"Biochemistry"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Pino, R., Badalamenti, N., Dall\u2019Acqua, S., Tundis, R., Bruno, M., Sottile, F., Sut, S., and Loizzo, M.R. (2025). Opuntia stricta (Haw.) Fruit Pulp and Seeds as Source of Bioactive Phytochemicals with Promising Functional Properties. Molecules, 30.","DOI":"10.3390\/molecules30071580"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1042\/bj3460201","article-title":"Crystal Structures of Human Pancreatic Alpha-Amylase in Complex with Carbohydrate and Proteinaceous Inhibitors","volume":"346","author":"Nahoum","year":"2000","journal-title":"Biochem. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"154740","DOI":"10.1016\/j.phymed.2023.154740","article-title":"Ameliorative Effects of Mangiferin Derivative TPX on Insulin Resistance via PI3K\/AKT and AMPK Signaling Pathways in Human HepG2 and HL-7702 Hepatocytes","volume":"114","author":"Fan","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Moon, D.O. (2024). Plant-Derived Flavonoids as AMPK Activators: Unveiling Their Potential in Type 2 Diabetes Management through Mechanistic Insights, Docking Studies, and Pharmacokinetics. Appl. Sci., 14.","DOI":"10.3390\/app14198607"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"120960","DOI":"10.1016\/j.jep.2025.120960","article-title":"Gegen Qinlian Decoction Ameliorates Insulin Resistance in Type 2 Diabetes: A Systematic Review and Meta-Analysis of RCTs with Mechanistic Insights into SIRT1\/AMPK Pathway Activation","volume":"358","author":"Liao","year":"2026","journal-title":"J. Ethnopharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s12986-021-00621-9","article-title":"The Anti-Diabetic Effects of Betanin in Streptozotocin-Induced Diabetic Rats through Modulating AMPK\/SIRT1\/NF-\u039aB Signaling Pathway","volume":"18","author":"Abedimanesh","year":"2021","journal-title":"Nutr. Metab."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Lee, H.S., Choi, S.M., Lim, S.H., and Choi, C.-I. (2023). Betanin from Beetroot (Beta vulgaris L.) Regulates Lipid Metabolism and Promotes Fat Browning in 3T3-L1 Adipocytes. Pharmaceuticals, 16.","DOI":"10.3390\/ph16121727"},{"key":"ref_36","first-page":"539","article-title":"Betanin as a Multipath Oxidative Stress and Inflammation Modulator: A Beetroot Pigment with Protective Effects on Cardiovascular Disease Pathogenesis","volume":"62","author":"Baiao","year":"2021","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nrd2850","article-title":"Assessing the Potential of Glucokinase Activators in Diabetes Therapy","volume":"8","author":"Matschinsky","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s00395-023-01018-w","article-title":"The Role of Glycolytic Metabolic Pathways in Cardiovascular Disease and Potential Therapeutic Approaches","volume":"118","author":"Chen","year":"2023","journal-title":"Basic Res. Cardiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/j.str.2004.02.005","article-title":"Structural Basis for Allosteric Regulation of the Monomeric Allosteric Enzyme Human Glucokinase","volume":"12","author":"Kamata","year":"2004","journal-title":"Structure"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Faloye, K.O., Bekono, B.D., Fakola, E.G., Ayoola, M.D., Bello, O.I., Olajubutu, O.G., Owoseeni, O.D., Mahmud, S., Alqarni, M., and Al Awadh, A.A. (2021). Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach. Molecules, 26.","DOI":"10.3390\/molecules26237211"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Saddala, M.S., Lennikov, A., and Huang, H. (2020). Discovery of Small-Molecule Activators for Glucose-6-Phosphate Dehydrogenase (G6PD) Using Machine Learning Approaches. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041523"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0022-2836(79)90416-9","article-title":"Crystal Structure of Cat Muscle Pyruvate Kinase at a Resolution of 2.6 A","volume":"134","author":"Stuart","year":"1979","journal-title":"J. Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1016\/j.biopha.2017.01.146","article-title":"Ameliorating Effect of Betanin, a Natural Chromoalkaloid by Modulating Hepatic Carbohydrate Metabolic Enzyme Activities and Glycogen Content in Streptozotocin\u2013Nicotinamide Induced Experimental Rats","volume":"88","author":"Dhananjayan","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"130303","DOI":"10.1016\/j.bbagen.2023.130303","article-title":"Sulfathiazole Treats Type 2 Diabetes by Restoring Metabolism through Activating CYP19A1","volume":"1867","author":"Hu","year":"2023","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"121314","DOI":"10.1016\/j.lfs.2022.121314","article-title":"Krebs Cycle Enzymes for Targeted Therapeutics and Immunotherapy for Anti-Leishmanial Drug Development Using: Pathways, Potential Targets, and Future Perspectives","volume":"322","author":"Ranjan","year":"2023","journal-title":"Life Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"155557","DOI":"10.1016\/j.phymed.2024.155557","article-title":"Protective Effect of Alizarin on Vascular Endothelial Dysfunction via Inhibiting the Type 2 Diabetes-Induced Synthesis of THBS1 and Activating the AMPK Signaling Pathway","volume":"128","author":"Zhu","year":"2024","journal-title":"Phytomedicine"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/prot.10639","article-title":"A Method Using Active-site Sequence Conservation to Find Functional Shifts in Protein Families: Application to the Enzymes of Central Metabolism, Leading to the Identification of an Anomalous Isocitrate Dehydrogenase in Pathogens","volume":"55","author":"Das","year":"2004","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_48","first-page":"96","article-title":"Molecular Evolution of the Vertebrate Hexokinase Gene Family: Identification of a Conserved Fifth Vertebrate Hexokinase Gene","volume":"3","author":"Irwin","year":"2008","journal-title":"Comp. Biochem. Physiol. Part D Genom. Proteom."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/0079-6107(93)90001-Z","article-title":"Evolution of Glycolysis","volume":"59","author":"Michels","year":"1993","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"27879","DOI":"10.1074\/jbc.271.44.27879","article-title":"Characterization of the AMP-Activated Protein Kinase Kinase from Rat Liver and Identification of Threonine 172 as the Major Site at Which It Phosphorylates AMP-Activated Protein Kinase","volume":"271","author":"Hawley","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/S0003-2697(02)00379-2","article-title":"Simplified Para-Nitrophenyl Palmitate Assay for Lipases and Esterases","volume":"311","author":"Gupta","year":"2002","journal-title":"Anal. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1515\/CCLM.1999.154","article-title":"Evaluation of a Direct Alpha-Amylase Assay Using 2-Chloro-4-Nitrophenyl-Alpha-D-Maltotrioside","volume":"37","author":"Lorentz","year":"1999","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_53","first-page":"79","article-title":"Biochemical and Molecular Characterization of Variant Pyruvate Kinase Enzymes and Genes from Three Patients with Red Blood Cell Pyruvate Kinase Deficiency","volume":"86","author":"Johnson","year":"1991","journal-title":"Acta Haematol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Hu, C., Zeng, Z., Ma, D., Yin, Z., Zhao, S., Chen, T., Tang, L., and Zuo, S. (2022). Discovery of Novel IDH1-R132C Inhibitors through Structure-Based Virtual Screening. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.982375"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.mito.2010.03.001","article-title":"Succinate Dehydrogenase\u2014Assembly, Regulation and Role in Human Disease","volume":"10","author":"Rutter","year":"2010","journal-title":"Mitochondrion"},{"key":"ref_56","first-page":"257","article-title":"Malate Dehydrogenases\u2014Structure and Function","volume":"21","year":"2002","journal-title":"Gen. Physiol. Biophys."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1006\/jmbi.1993.1122","article-title":"Molecular Basis of Allosteric Activation of Bacterial L-Lactate Dehydrogenase","volume":"230","author":"Iwata","year":"1993","journal-title":"J. Mol. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1002\/pro.5560040908","article-title":"The Structure of Human Pancreatic Alpha-Amylase at 1.8 A Resolution and Comparisons with Related Enzymes","volume":"4","author":"Brayer","year":"1995","journal-title":"Protein Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"32539","DOI":"10.1074\/jbc.M706543200","article-title":"Defining the Mechanism of Activation of AMP-Activated Protein Kinase by the Small Molecule A-769662, a Member of the Thienopyridone Family","volume":"282","author":"Sanders","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, Efficient Optimization, and Multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/0047-6374(83)90084-2","article-title":"The Age-Dependent Metabolic Decline of the Red Blood Cell","volume":"22","author":"Magnani","year":"1983","journal-title":"Mech. Ageing Dev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1016\/S0041-1345(02)03463-2","article-title":"Production of Oxygen Free Radicals and of Hemolysis by Cyclosporine","volume":"Volume 34","author":"Kwak","year":"2002","journal-title":"Transplantation Proceedings"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/6\/947\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T01:00:34Z","timestamp":1781744434000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/6\/947"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,16]]},"references-count":62,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ph19060947"],"URL":"https:\/\/doi.org\/10.3390\/ph19060947","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,16]]}}}