MMSL 2023, 92(1):2-13 | DOI: 10.31482/mmsl.2022.013

BIOCHEMICAL STUDY OF SERUM β-HYDROXYBUTYRATE DEHYDROGENASE IN β-THALASSEMIAOriginal article

Hiba N. Sami ORCID...1, Mahmoud A. M. Fakhri ORCID...2*
1 Department of Chemistry, College of Science, University of Mosul, Iraq
2 Department of Biophysics, College of Science, University of Mosul, Iraq

Introduction: Thalassemia is a healthcare challenging disease all over the world. It imparts a great burden on patients’ families and healthcare institutions. Scientists focus on new aspects to overcome these challenges and increase patient tolerance of disease complications. This study aims to quantify β-Hydroxybutyrate Dehydrogenase BHBDH activity in thalassemia patients compared to the control group and their correlation with the patient's demographic characteristics.

Methods: To do so, serum was collected from patients and the control group and analyzed biochemically for targeted laboratory tests. We determined β-Hydroxybutyrate Dehydrogenase from normal human serum using biochemical molecular techniques.

Results: The results showed that BHBDH activity is significantly higher in the patients compared to the control group regardless of age, sex, or marital status. The results confirmed that enzyme activity and the purification folds were (0.0214 U/ml) and (51.7) respectively for the partially purified enzyme. Furthermore, the proportional molecular weight of the incompletely isolated β-Hydroxybutyrate Dehydrogenase was (125.8±0.5 kDa) using gel filtration chromatography. The comparative molecular weight of the subunit of partially isolated β-Hydroxybutyrate Dehydrogenase was (32.1±0.5 kDa) using SDS–PAGE.

Conclusion: we demonstrate that BHBDH enzymatic activity is higher than control and this could be a prognostic or diagnostic tool in thalassemia patients.

Keywords: β-Thalassemia; β-Hydroxybutyrate Dehydrogenase; Myeloperoxidase; isolation; purification

Received: January 20, 2022; Revised: March 9, 2022; Accepted: March 10, 2022; Prepublished online: March 31, 2022; Published: March 3, 2023  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Sami, H.N., & Fakhri, M.A.M. (2023). BIOCHEMICAL STUDY OF SERUM β-HYDROXYBUTYRATE DEHYDROGENASE IN β-THALASSEMIA. MMSL, 92(1), 2-13. doi: 10.31482/mmsl.2022.013
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Galanello R, Origa R. Beta-thalassemia. Orphanet journal of rare diseases. 2010 Dec;5(1):1-5. https://doi.org/10.1186/1750-1172-5-11 Go to original source... Go to PubMed...
    2. Olivieri NF. The β-thalassemias. New England journal of medicine. 1999 Jul 8;341(2):99-109. https://doi.org/10.1056/NEJM199907083410207 Go to original source... Go to PubMed...
    3. Authored by Dr Colin Tidy, Reviewed by Dr Adrian Bonsall | Last edited 22 Jan 2018 | Meets Patient's editorial guidelines
    4. Angastiniotis M, Lobitz S. Thalassemias: an overview. International Journal of Neonatal Screening. 2019 Mar;5(1):16. https://doi.org/10.3390/ijns5010016 Go to original source... Go to PubMed...
    5. Żoŀnierowicz S, Świerczyński J, Żelewski L. β-Hydroxybutyrate dehydrogenase activity in human placenta. Placenta. 1984 Mar 1;5(2):183-7. https://doi.org/10.1016/S0143-4004(84)80061-2 Go to original source... Go to PubMed...
    6. Ali BA, Mahmoud AM. Frequency of glomerular dysfunction in children with beta thalassaemia major. Sultan Qaboos University Medical Journal. 2014 Feb;14(1):e88. https://doi.org/10.12816/0003341 Go to original source... Go to PubMed...
    7. Kohgo Y, Ikuta K, Ohtake T, et al. Body iron metabolism and pathophysiology of iron overload. International journal of hematology. 2008 Jul;88(1):7-15. https://doi.org/10.1007/s12185-008-0120-5 Go to original source... Go to PubMed...
    8. Sharma DC, Arya A, Kishor P, et al. Overview on thalassemias: a review article. Medico Research Chronicles. 2017 Jun 30;4(03):325-37.
    9. Rasool M, Malik A, Jabbar U, et al. Effect of iron overload on renal functions and oxidative stress in beta thalassemia patients. Saudi medical journal. 2016 Nov;37(11):1239. https://doi.org/10.15537/smj.2016.11.16242 Go to original source... Go to PubMed...
    10. Papanikolaou G, Tzilianos M, Christakis JI, et al. Hepcidin in iron overload disorders. Blood. 2005 May 15;105(10):4103-5. https://doi.org/10.1182/blood-2004-12-4844 Go to original source... Go to PubMed...
    11. Stillwell, William (2016). An Introduction to Biological Membranes || Lipid Membrane Properties. , 181-220. doi:10.1016/B978-0-444-63772-7.00010-5 Go to original source...
    12. Żoŀnierowicz S, Świerczyński J, Żelewski L. β-Hydroxybutyrate dehydrogenase activity in human placenta. Placenta. 1984 Mar 1;5(2):183-7. https://doi.org/10.1016/S0143-4004(84)80061-2 Go to original source... Go to PubMed...
    13. Akil O, El Kebbaj Z, Latruffe N, et al. D-3-hydroxybutyrate oxidation in mitochondria by D-3-Hydroxybutyrate dehydrogenase in Tetrahymena pyriformis. African Journal of Biochemistry Research. 2009 Mar 31;3(3):029-36. https://doi.org/10.5897/AJBR.9000069 Go to original source...
    14. Otsuka H, Kimura T, Ago Y, et al. Deficiency of 3-hydroxybutyrate dehydrogenase (BHBDH1) in mice causes low ketone body levels and fatty liver during fasting. Journal of inherited metabolic disease. 2020 Sep;43(5):960-8. https://doi.org/10.1002/jimd.12243 Go to original source... Go to PubMed...
    15. Lawlor DA, Day IN, Gaunt TR, et al. The association of the PON1 Q192R polymorphism with coronary heart disease: findings from the British Women's Heart and Health cohort study and a meta-analysis. BMC genetics. 2004 Dec;5(1):1-2.https://doi.org/10.1186/1471-2156-5-17 Go to original source... Go to PubMed...
    16. Romani A, Trentini A, van der Flier WM, et al. Arylesterase activity of paraoxonase-1 in serum and cerebrospinal fluid of patients with Alzheimer's disease and vascular dementia. Antioxidants. 2020 May;9(5):456. https://doi.org/10.3390/antiox9050456 Go to original source... Go to PubMed...
    17. Hussein GM. Evaluation of Paraoxonase1 Activities and Lipid Profiles Concentration in Sera of β-Thalassemia Major Patients. Evaluation. 2017;4(1):14-22.
    18. Kabaroglu C, Mutaf II, Boydak B, et al. Association between serum paraoxonase activity and oxidative stress in acute coronary syndromes. Acta cardiologica. 2004 Dec 1;59(6):606-11. Go to original source... Go to PubMed...
    19. Panachan J, Chokchaichamnankit D, Weeraphan C, et al. Differentially expressed plasma proteins of β-thalassemia/hemoglobin E patients in response to curcuminoids/vitamin E antioxidant cocktails. Hematology. 2019 Jan 1;24(1):300-7. https://doi.org/10.1080/16078454.2019.1568354 Go to original source... Go to PubMed...
    20. Khan AA, Alsahli MA, Rahmani AH. Myeloperoxidase as an active disease biomarker: recent biochemical and pathological perspectives. Medical sciences. 2018 Jun;6(2):33. https://doi.org/10.3390/medsci6020033 Go to original source... Go to PubMed...
    21. Arnhold J. Properties, functions, and secretion of human myeloperoxidase. Biochemistry (Moscow). 2004 Jan;69(1):4-9. https://doi.org/10.1023/B:BIRY.0000016344.59411.ee Go to original source... Go to PubMed...
    22. Liu WQ, Zhang YZ, Wu Y, et al. Myeloperoxidase-derived hypochlorous acid promotes ox-LDL-induced senescence of endothelial cells through a mechanism involving β-catenin signaling in hyperlipidemia. Biochemical and biophysical research communications. 2015 Nov 27;467(4):859-65. https://doi.org/10.1016/j.bbrc.2015.10.053 Go to original source... Go to PubMed...
    23. Klebanoff SJ. Myeloperoxidase: friend and foe. Journal of leukocyte biology. 2005 May;77(5):598-625. https://doi.org/10.1189/jlb.1204697 Go to original source... Go to PubMed...
    24. Le, Tao (2021). First Aid for the USMLE Step 1 (2021 ed.). New York: McGraw Hill. p. 109. ISBN 9781260467529.
    25. Heinecke JW, Li W, Francis GA, et al. Tyrosyl radical generated by myeloperoxidase catalyzes the oxidative cross-linking of proteins. The Journal of clinical investigation. 1993 Jun 1;91(6):2866-72. https://doi.org/10.1172/JCI116531 Go to original source... Go to PubMed...
    26. Davies, Michael Davies; Hawkins, Clare L. (2020). The role of myeloperoxidase (MPO) in biomolecule modification, chronic inflammation and disease.. Antioxidants & Redox Signaling, (), ars.2020.8030-. doi:10.1089/ars.2020.8030. Go to original source... Go to PubMed...
    27. Tal S, Smirnoff P, Okon Y. Purification and characterization of D (-)-β-hydroxybutyrate dehydrogenase from Azospirillum brasilense Cd. Microbiology. 1990 Apr 1;136(4):645-9. https://doi.org/10.1099/00221287-136-4-645 Go to original source...
    28. Kumar P, Pai K, Pandey HP, et al. NADH-oxidase, NADPH-oxidase and myeloperoxidase activity of visceral leishmaniasis patients. Journal of medical microbiology. 2002 Oct 1;51(10):832-6. https://doi.org/10.1099/0022-1317-51-10-832 Go to original source... Go to PubMed...
    29. Tomás M, Sentí M, Garcîa-Faria F, et al. Effect of simvastatin therapy on paraoxonase activity and related lipoproteins in familial hypercholesterolemic patients. Arteriosclerosis, thrombosis, and vascular biology. 2000 Sep;20(9):2113-9. https://doi.org/10.1161/01.ATV.20.9.2113 Go to original source... Go to PubMed...
    30. Fischbach F. (2000) ."A Manual of Laboratory and Diagnostic Test"." 6th ed. Lippincott Williams and Wilkins, U.S.A. ,p: 472
    31. Richterich R.(1969)." Clinical Chemistry Theory and Practice " .S. Karger A.G. Basel, Switzerland, pp: 245-249
    32. Scimone J. and Rothstein R (1978)." Laboratory Manual of Clinical Chemistry" . AVI Puplishing company . Inc., U.S.A., pp: 60,63.
    33. D'haese PC, Lamberts LV, Vanheule AO, et al. Direct determination of zinc in serum by Zeeman atomic absorption spectrometry with a graphite furnace. Clinical chemistry. 1992 Dec 1;38(12):2439-43. https://doi.org/10.1093/clinchem/38.12.2439 Go to original source... Go to PubMed...
    34. Plummer, T.D.( 1978) "An Introduction of Practical Biochemistry". 2nd ed. McGraw-Hill Book Co.U.K.: pp: 48,53,174,270,274.
    35. Khawaji MM, Hazzazi AA, Ageeli MH, et al. Clinical and hematological features among β-thalassemia major patients in Jazan region: A hospital-based study. Journal of family medicine and primary care. 2020 Jan;9(1):412. https://doi.org/10.4103/jfmpc.jfmpc_1007_19 Go to original source... Go to PubMed...
    36. Kadhem Abeid A. Physiological study for some blood parameters in children with major B-Thalassemia in Al-Najaf governorate/Iraq. journal of kerbala university. 2014 Apr 1;10(1):170-8.
    37. Asif M, Manzoor Z, Farooq MS, et al. Status of oxidant, antioxidantand serum enzymes in thalassaemic children receiving multiple blood transfusions. J Pak Med Assoc. 2015 Aug 1;65(8):838-43. Go to PubMed...
    38. Tripathi P, Agarwal S, Tewari S, et al. Status of Catalase, Glutathione Peroxidase, Glutathione S-Transferase, and Myeloperoxidase Gene Polymorphisms in Beta-Thalassemia Major Patients to Assess Oxidative Injury and Its Association with Enzyme Activities. Journal of Pediatric Genetics. 2021 Apr 12. https://doi.org/10.1055/s-0041-1723961 Go to original source... Go to PubMed...
    39. Abd IK, Zainal IG. Assessment of biochemical parameters and study its correlation in ß-Thalassemia major patients and healthy controls in Kirkuk City, Iraq. Medical Journal of Babylon. 2020 Apr 1;17(2):172. https://doi.org/10.4103/MJBL.MJBL_77_19 Go to original source...
    40. Ghone RA, Kumbar KM, Suryakar AN, et al. Oxidative stress and disturbance in antioxidant balance in beta thalassemia major. Indian Journal of Clinical Biochemistry. 2008 Oct;23(4):337-40. https://doi.org/10.1007/s12291-008-0074-7 Go to original source... Go to PubMed...
    41. El-Kaream SA, Ebied SA, Sadek NA. Serum tartrate resistant acid phosphatase 5b in beta Thalassemia Egyptian patients: promising biomarker of iron overload oxidative stress and bone disease. Ann Clin Lab Res. 2019;7(2):303. https://doi.org/10.21767/2386-5180.100303 Go to original source...
    42. Smesam Hasan NK, Albuthabhak Hasan AQ, Arjmand Sareh, et al (2020). Evaluation of Erythroferrone, Hepcidin, and Iron Overload Status in Iraqi Transfusion-Dependent Î<sup>2</sup>-Thalassemia Major Patients. Hemoglobin, (), 1-6. https://doi.org/10.1080/03630269.2020.1794888 Go to original source... Go to PubMed...
    43. Ghorban K, Shanaki M, Mobarra N, et al. Apolipoproteins A1, B, and other prognostic biochemical cardiovascular risk factors in patients with beta-thalassemia major. Hematology. 2016 Feb 7;21(2):113-20. https://doi.org/10.1179/1607845415Y.0000000016 Go to original source... Go to PubMed...
    44. Bordbar M, Haghpanah S, Afrasiabi A, et al. Genotype-phenotype correlation related to lipid profile in beta-thalassemia major and intermedia in southern Iran. Journal of clinical lipidology. 2012 Mar 1;6(2):108-13. https://doi.org/10.1016/j.jacl.2011.12.005 Go to original source... Go to PubMed...
    45. Karim MF, Ismail M, Hasan AM, et al. Hematological and biochemical status of Beta-thalassemia major patients in Bangladesh: A comparative analysis. International journal of hematology-oncology and stem cell research. 2016 Jan 1;10(1):7. Go to PubMed...
    46. Mehdizadeh M, Zamani G, Tabatabaee S. Zinc status in patients with major β-thalassemia. Pediatric hematology and oncology. 2008 Jan 1;25(1):49-54. https://doi.org/10.1080/08880010701773738 Go to original source... Go to PubMed...
    47. Alsharnoubi J, Nassef Y, Fahmy RF, et al. Using LIBS as a diagnostic tool in pediatrics beta-thalassemia. Lasers in Medical Science. 2021 Jul;36(5):957-63. https://doi.org/10.1007/s10103-020-03117-9 Go to original source... Go to PubMed...
    48. Abdulla AA. Evaluation of serum antioxidant enzymes in β-thalassemia major patients. International Journal of ChemTech Research. 2018;11(7):323-8.http://dx.doi.org/10.20902/IJCTR.2018.110738 Go to original source...
    49. Kargapolova Y, Geißen S, Zheng R, et al. The Enzymatic and Non-Enzymatic Function of Myeloperoxidase (MPO) in Inflammatory Communication. Antioxidants. 2021 Apr;10(4):562. https://doi.org/10.3390/antiox10040562 Go to original source... Go to PubMed...
    50. Balci YI, Ünak Ş, Gümrük F. Serum Lipids in Turkish Patients with β-Thalassemia Major and β-Thalassemia Minor. https://doi.org/10.4274/tjh.2015.0168 Go to original source... Go to PubMed...
    51. Kumar Tarun, Basu Surupa, Kundu Ritabrata, et al (2020). Lipid Profile in Children With Thalassemia: A Prospective Observational Study From Eastern India. Indian Pediatrics, 57(11), 1072-1073. https://doi.org/10.1007/s13312-020-2040-2 Go to original source...
    52. Marks AR, McIntyre JO, Duncan TM, et al. Molecular cloning and characterization of (R)-3-hydroxybutyrate dehydrogenase from human heart. Journal of Biological Chemistry. 1992 Aug 5;267(22):15459-63. https://doi.org/10.1016/S0021-9258(19)49556-2 Go to original source...

    Return to the content