Discipline - Biochemistry

Professor Margina Denisa Marilena, PhD tenured
Professor Gradinaru Daniela, PhD tenured
Associate Professor Dragoi Cristina-Manuela, PhD tenured
Associate Professor Nicolae Alina-Crenguta, PhD tenured
Head of works Ungurianu Anca, PhD tenured

From the very beginning of pharmaceutical education in our country (1857), Biochemistry, although only recently established as a science worldwide, has developed conommitently in the domain of education as well as that of research, with two major aspects: General Biochemistry and Applied Biochemistry, respectively Medical Biochemistry and Alimentary Biochemistry.

Notions about biochemistry have evolved, being taught to students in various forms – Biological Chemistry Laboratory, Food and Drink Analysis, Biological and Alimentary Chemistry – allowing the individualization of the Biochemistry Discipline. All of these transformations have occured under the guidance of famous romanian science professors, such as: Alexandru lonescu-Matiu, I. Vintilescu, Constantin N. Lonescu, Dumitru Isăcescu, Aurora Popescu, Simion Căpâlnă, Ştefan Tămăşdan, and Matilda Rosetti-Colţoiu.

Biochemistry and the Chemistry of Sanitation were combined into one discipline until 1972, when they were separated. Senior lecturer Matilda Rosetti-Colţoiu, became the head of the discipline of Biochemistry, working together with a group consisting of: lecturer dr. Pharmacist Gh. Nuţă, teaching assistant pharmacist I. Feraru and modular assistents Niculina Mitrea and Olguţa Macovschi. During the period 1990-2011, prof. dr. pharmacist Niculina Mitrea coordinated the organizational, didactic and scientific activities within the discipline, constantly aiming to further develop the discipline, with a high level of devotion to her profession, collaborators and the students.

Didactic activities consist of lectures and practical lessons in Biochemistry; these are described in the analytical program for year III, semesters V and VI.

A firm understanding of the basic theoretical and practical notions, taught by the Biochemistry Discipline, is indispensible for understanding fundamental physiological and pathological mechanisms, as well as understanding the mechanism of action of different medications.

Likewise, the concepts taught during Biochemistry lectures create a theoretical basis for understanding topics taught by other pharmaceutical desciplines: pharmacology, toxicology, clinical laboratory and alimentary hygiene.

General objectives of Biochemistry lectures:

  • to teach various fundamental concepts of structural and dynammic biochemistry with respect to human intermediary metabolism (carbohydrate, lipid proteic and mineral);
  • processes which consume and provide energy;
  • homeostatic regulatory mechanisms; mechanisms of action of biochemical effectors – hormones, vitamins, enzymes, as regulating factors of metabolism in general;
  • biochemical mechanisms involved in different diseases and the mechanism of action of different medications.

Specific objectives of biochemistry lectures:

  • to teach theoretical concepts regarding the constituents of the human body;
  • human cellular biomolecules, physiological and metabolic processes occuring at the cellular and molecular level, the functioning of the human body as an anti-entropic, open biological system – the molecular logic of life;
  • to teach theoretical notions about the enzymatic systems present in human cells; enzymes as catalysts, influencing carbohydrate, lipid and protein metabolism; enzymatic inhibition as a mechanism of action in pharmacy.
  • to teach theoretical concepts regarding the structure and function of nucleic acids, protein biosynthesis, in order to understand the mechanism of action of medications at the genomic level, as well as notions of biotechnology;
  • to teach theoretical notions regarding the regulatory mechanisms of physiological and metabolic processes by signalling molecules – hormones and vitamins; concepts regarding vitamins, which constitute natural exogenous catalysts, and their involvement in intermediary metabolism.

Practical lessons in biochemistry aim to offer students theoretical and practical notions regarding the principles and techniques used to qualitatively and quantitatively explre the fundamental constituents of living matter.

The main objectives of the practical lessons are:

  • to understand the physical and chemical properties of the fundamental constituents of living matter – carbohydrates, lipids, proteins, nucleic acids;
  • identification and dosage methods of various biomolecules at the tissular, cellular and subcellular levels;
  • dosage of various components in biological fluids; in vitro exploration of some metabolic pathways and their interaction with medications;
  • the correct use and manipulation methods of biological material and biological probes, instruments and biochemical devices;
  • to teach modern techniques used in biochemical analysis and evaluation of the actions of medications: spectrophotometry, spectrofluorometry, electrophoresis, chromatography, and immunohistochemistry techniques.

Over the last few years research activities of the teaching personnel within the Discipline have been based on optimizing the methodology used to investigate the biochemical mechanisms implicated in pathophysiological processes and in the actions of medications.

Main areas of research conducted within the discipline include:

  • biochemistry of oxidative stress in aging and in pathologies associated with senescence;
  • the effect of natural and synthetic compounds on cellular membranes and artificial membranes;
  • biochemical modulation of endogenous neuroendocrine systems;
  • biochemical mechanisms implicated in multi-drug resistance;
  • modulation of the blood-brain-barrier in the pharmacotherapy of chronic disease;
  • biochemical mechanisms of action of biological medications.

Biochemistry course content, year III, semester V

  1. INTRODUCTION TO DYNAMIC BIOCHEMISTRY (2 hours)
  • 1.1. Biochemistry content, importance and relationship with other pharmaceutical disciplines.
  • 1.2. Chemical composition and organization of living matter. Molecular logic of life.
  • 1.3. Dynamic characteristics of biological processes. The living organism – biological systems and subsystems. Biochemical thermodynamics.

2. ENZYMES (12 hours)

  • 2.1 General notions about enzymes. Catalytic characteristics of enzymes. Factors influencing the speed of an enzymatic reaction. Tissular and intracellular repartition of enzymes.
  • 2.2. Enzymatic structure. Enzyme cofactors. Coenzymes. Prosthetic groups.
  • 2.3. Enzyme classification. Nomenclature. Description of individual enzymes in the following classes: oxidases/reducatases, transferases, hydrolases, lyases, isomerases, ligases. Their biological role. Biochemical mechanisms regarding coenzymes for each class of enzymes.
  • 2.4. Enzymatic inhibition. Pharmaceutical enzymatic inhibitors.
  • 2.5. Enzymes in the context of medicine and pharmacy. Biochemical mechanisms of enzymopathies.
  1. INTRODUCTION TO INTERMEDIARY METABOLISM (4 hours)
  • 3.1 General mechanisms of transformation of the fundamental organic constituents of living matter. Notions of bioenergy in living cells.
  • 3.2. The citric acid cycle
  • 3.3. Biological mitochondrial oxidation
  • 3.4. Biological microsomal oxidation
  1. CARBOHYDRATE METABOLISM (12 hours)
  • 4.1. Main pathways of glucose degradation (aerobic, anaerobic, pentoso-phosphate and uronic acids pathways). Bioenergetics aspects in carbohydrate metabolism.
  • 4.2. Carbohydrate anabolism
  • 4.3. Mucopolysaccharide metabolism
  • 4.4. Pathological carbohydrate metabolism
  1. LIPID METABOLISM (12 hours)
  • 5.1  Degradation and biosynthesis of fatty acids. Triglyceride metabolism. Bioenergetic aspects of lipid metabolism.
  • 5.2. Glycerophosphatide metabolism
  • 5.3. Sphingolipid metabolism
  • 5.4. Steroid metabolism
  • 5.5. Biologically active lipids. Prostacyclins. Prostaglandins. Tromboxanes. Leucotrienes.
  • 5.6. Pathological lipid metabolism

Biochemistry course content, year III, semester VI

  1. PROTEIC METABOLISM (12 hours)
  • 1.1. General mechanisms of degradation and transformation of amino acids. Energetic metabolism of proteins.
  • 1.2. Metabolism of urea, glutamine, creatinine and creatine.
  • 1.3. Metabolism of individual amino acids. Pathological aspects.
  • 1.4. Metabolism of chromoproteins. Hemoglobinopathies.
  • 1.5. Metabolism of purine and oyrimidine nucleic acids.
  1. NUCLEIC ACIDS AND PROTEIN BIOSYNTHESIS (3 hours)
  • 2.1. Types of DNA and RNA. Their biological roles. DNA replication and transcription. The genetic code.
  • 2.2. Protein biosynthesis. Regulation and control mechanisms.
  1. BIOLOGICAL MECHANISMS OF REGULATION AND CONTROL IN LIVING ORGANISMS (3 hours)
  • 3.1. Aspects of intracellular and intercellular communication mechanisms.
  • 3.2. Regulation at the molecular and cellular level.
  • 3.3. Membrane and intracellular receptors, G proteins and secondary messengers.
  1. HORMONES AND HORMONAL REGULATION (15 hours)
  • 4.1. General concepts about endocrine glands and hormones. Classification of hormones. Hormonal mechanisms of action at the cellular level.
  • 4.2. Polypeptide hormones (hypothalamic hormones, hypophyseal hormones, parathyroid hormones, pancreatic hormones and adipocyte hormones).
  • 4.3. Amino acid derived hormones (adrenal and thyroid hormones).
  • 4.4. Steroid hormones
  • 4.5. Local tissular hormones. The autocrine system. Eicosanoids.
  1. REGULATION OF INTERMEDIARY METABOLISM THROUGH VITAMINS (6 hours)
  • 5.1. Hydrosoluble vitamins (thiamine, riboflavin, pyridoxine, folic acid, pantothenic acid, cobalamin, ascorbic acid).
  • 5.2. Liposoluble vitamins (retonoids, tocopherols, calciferols, naphthoquinones)
  1. CHEMICAL MEDIATORS AND MODULATORS OF THE NERVE IMPULSE (3 hours)
  • 6.1. Active biological amines.
  • 6.2. Active biological polypeptides.

Bibliography – Lecture

  1. Niculina Mitrea, Andreea Arsene, Denisa Margina, Daniela Gradinaru - Biochimie. Enzimele in procesele metabolice, Editura Universitara „Carol Davila", Bucuresti, 2010, 258 pagini, ISBN 978 – 973-708-495-8
  1. Niculina Mitrea, Denisa Margina, Daniela Gradinaru, Andreea Arsene, Calin Burta - Biochimie. Vitaminele in procese metabolice, Editura Didactica si Pedagogica, Bucuresti, 2008, 551 pagini, ISBN 978-973-30-2037-0
  1. Dinu Veronica, E. Trutia, Elena Cristea Popa, Aurora Popescu – Biochimie medicala. Mic tratat, Ed. Medicala Bucuresti, 2001
  1. Nelson David L, Cox M. Michael – Lehninger’s Principles of Biochemistry, W. H. Freeman and Company, New York, 2013
  1. Lubert Stryer – Biochemistry, W. H. Freeman and Company, New York, 2010
  1. Voet D., Voet J. G. – Biochemistry, John Wiley and Sons, 2013
  1. Lippincott’s Illustrated Reviews – Biochemistry, Lippincott Williams & Wilkins, 2014
  1. Devlin M.T. - Textbook of Biochemistry with Clinical Correlations, Sixth Edition, Wiley-Liss., Hoboken, NY, 2010

Bibliography – Practical Lessons

  1. Investigatii biochimice – Enzime - Niculina Mitrea-Vasilescu, Adrian Andries, Denisa Margina, Daniela Gradinaru, Ion Feraru, Andreea Letitia Arsene, Editura Universitara „Carol Davila", 2009
  1. Investigatii biochimice –Partea a-II-a - Metabolismul glucidelor si al lipidelor - Niculina Mitrea-Vasilescu, Denisa Margina, Daniela Gradinaru, Ion Feraru, Adrian Andries, Andreea Nitulescu-Arsene, Editura Universitara „Carol Davila", 2009
  1. Investigatii biochimice –Partea a-III-a - Metabolismul aminoacizilor si al proteinelor- Niculina Mitrea-Vasilescu, Daniela Gradinaru, Adrian Andries, Ion Feraru, Denisa Margina, Andreea Nitulescu-Arsene, Editura Universitara „Carol Davila", Bucuresti, 2009
  1. Investigatii biochimice, Partea IV. Hormoni si vitamine - Niculina Mitrea-Vasilescu, Andreea Nitulescu-Arsene, Denisa Margina, Daniela Gradinaru, Adrian Andries, Ion Feraru, Editura Universitara „Carol Davila", Bucuresti, 2009

At the level of the Discipline, there is a Biochemistry Module available for pharmacy residents, specializing in Clinical Pharmacy and Pharmaceutical Laboratory.

The lecture topics included in the Biochemistry Module for residents consist in:

  • biochemical mechanisms associated with oxidative stress
  • biochemical and immunological markers of acid-base balance
  • biochemistry of inflammation
  • biochemical and immunological markers of inflammation
  • biochemical disturbances associated with obesity
  • adipose tissue hormones
  • biochemical mechanisms implicated in the body’s resistence to certain medications
  • theories of aging and anti-aging therapies
  • biomarkers of cellular senescence.

Bibliography

  1. Daniela Gradinaru - Biochimia stresului oxidativ in patologia asociata imbatranirii, Editura Ars Academica, Bucuresti (2013) ISBN 978-606-8017-87-7
  2. Denisa Margina - Biochimia tesutului adipos. Volumul I -  Biomolecule cu rol orexigen; Volumul II - Biomolecule cu rol anorexigen si protector, Editura Printech, Bucuresti (2015) ISBN 978-606-23-0507-9, ISBN 978-606-23-0507-6
  3. Cristina Manuela Dragoi - Tryptophan, serotonin, melatonin - the spectacular triad: physiological, pathological and therapeutic implications of some bio-compounds with indolic structure, LAP LAMBERT Academic Publishing (2013), ISBN-10:3659404934, ISBN-13: 978-3659404931
  4. Alina Crenguta Nicolae - P-glycoprotein and the development of multidrug resistance, LAP LAMBERT Academic Publishing (2014), ISBN 978-3-659-63449-9
  • Oxidative stress
  • Senescence
  • Bioflavanoids
  • Adipobiology
  • Melatonin
  • Multi-drug resistance
  • Blood brain barrier
  • Biological medications

International Projects

  1. Daniela Grădinaru – Director de proiect din partea Institulului Naţional de Gerontologie şi Geriatrie „Ana Aslan”, la proiectul finanţat de Comisia Europeană pentru Cercetare, în cadrul Programului 7th European Framework Research Project – FP7 Health MARK-AGE: “European study to establish biomarkers of human ageing” (durata de desfășurare- 5 ani; 2008 – 2013)
  2. Denisa Margină – Director al proiectului internațional „Studies regarding certain biological effects of encapsulated vegetal extracts from plants with known cardio-vascular positive outcome”, câștigat prin competiție internațională, finanțat de compania farmaceutică BIONORICA (Germania), în cadrul acțiunii Global Research Initiative – 2014 (durata de desfășurare-12 luni, 2014-2015).

National Projects

  1. Denisa Margină – Director de proiect, Programul PNII–Capacităţi, proiectul PD 132/30.07.2010: „Studii privind efectul unor polifenoli asupra mecanismelor celulare implicate în dezvoltarea complicatiilor cardio-vasculare ale hiperglicemiei cronice”, coordonat şi finanţat de CNCSIS (durata de desfăşurare- 24 luni, 2010-2012).
  2. Denisa Margină – Responsabil de proiect din partea UMF „Carol Davila” în cadrul proiectului de cercetare PNII de tip Parteneriate (PC direcţia 4), nr 41-067/2007, „Studiul mecanismelor celulare, moleculare si genice prin care dislipidemia induce rezistenta la insulina; identificarea de compusi probiotici activi si metode de tratament”, desfăşurat sub coordonarea Institutului de Biologie şi Patologie Celulară N. Siminonescu, Director de proiect: cercetător ştiinţific gr I Anca V. Sima (durata de desfăşurare- 3 ani, 2007-2010).
  3. Cristina Manuela Drăgoi – director de proiect de cercetare câștigat prin competiție internă UMF Carol Davila „Cercetări privind proiectarea și evaluarea fizico-chimică și biologică a unor sisteme multiparticulate cu potențial efect antiaterogen”- (durata de desfășurare-24 luni, 2014-2016).
  4. Alina Crenguța Nicolae – membru în colectivul de cercetare în proiectul: “Produse terapeutice inovative cu acțiune profilactică și curativă destinate sectorului zoo-veterinar” (SANOVET). Instituția coordonatoare: Universitatea de Stiinte Agronomice si Medicina Veterinara (USAMV), Bucuresti.
  1. Gradinaru D., Borsa C., Ionescu C., Prada G.I. – Oxidized LDL and NO synthesis -Biomarkers of endothelial dysfunction and ageing – Mechanisms of Ageing and Development, 2015, 151:101-13. doi: 10.1016/j.mad.2015.03.003.
  2. Gradinaru D., Margina D., Ilie M., Borsa C., Ionescu C., Prada G.I. – Correlation between erythropoietin serum levels and erythrocyte susceptibility to lipid peroxidation in elderly with type 2 diabetes – Acta Physiologica Hungarica, 2015, 102(4):400-408. doi: 10.1556/036.102.2015.4.7.
  3. Gradinaru D., Borsa C., Ionescu C., Margina D. – Advanced oxidative and glycoxidative protein damage markers in elderly with type 2 diabetes, Journal of Proteomics, 2013, 92:313-322. doi: 10.1016/j.jprot.2013.03.034.
  4. Margina D., Olaru O.T., Ilie M., Gradinaru D., Gutu C., Voicu S., Dinischiotu A., Spandidos D.A., Tsatsakis A.M. – Assessment of the potential health benefits of certain total extracts from Vitis vinifera, Aesculus hyppocastanum and Curcuma longa, Experimental and Therapeutic Medicine, 2015, 10:1681-1688. doi:10.3892/etm.2015.2724
  5. Margina D., Ilie M., Gradinaru D., Androutsopoulos VP., Kouretas D., Tsatsakis AM. – Natural products –friends or foes? Toxicology Letters, 2015, 236:154–167. doi: 10.1016/j.toxlet.2015.05.009.
  6. Margina D., Ilie M., Manda G., Neagoe I., Danciulescu-Miulescu R., Purdel C.N., Gradinaru D. – Long term in vitro effects of quercetin and epigallocatechin gallate on cell membrane parameters, Cellular and Molecular Biology Letters, 2014, 19:542-560, DOI: 10.2478/s11658-014- 0211-7.
  7. Nicolae A.C., Drăgoi C.M., Ceaușu I., Poalelungi C., Iliescu D., Arsene A.L. – Clinical implications of the indolergic system and oxidative stress in physiological gestational homeostasis, FARMACIA, 2015, Vol 63 (1), 46-51, ISSN 0014-8237, IF 1,251/2013
  8. Nicolae A.C., Mitrea N., Drăgoi C.M., Constantinescu M.Z., Ciofrângeanu C., Bărboi G., Arsene A.L. – Murine studies regarding the variation of oxidative status in serum, hepatic and brain samples, after administration of some CNS active drugs, FARMACIA, 2013, Vol 61 (4), 658-669, ISSN 0014-8237, IF 1,251/2013 Nicolae A.C., Mitrea N., Arsene A.L., Constantinescu M.Z., Vuță V., Drăgoi C.M. – In vitro P-glycoprotein inhibition assay on N2a murine cell line, FARMACIA, 2013, Vol 61 (3), 481-491, ISSN 0014-8237, IF 0,578/2012
  9. Drăgoi C.M., Mitrea N., Arsene A.L., Nicolae A.C., Ilie M. – In vitro effects of some bio-indoles on the transmembrane potential of Jurkat E6.1 limphoblasts, FARMACIA, 2012, Vol.60(2), 240-248, ISSN 0014-8237, IF 0,578/2012

University of Medicine and Pharmacy "Carol Davila" Bucharest

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Fiscal code: 4192910
bank account: RO57TREZ70220F330500XXXX
Bank: Sector 2 Treasury

Phone:
+4021 3180719
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+4021 3180722
rectorat@umfcd.ro

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