MEDICAL CHEMISTRY

COURSE CODE:	ΒΕ0200
COURSE INSTRUCTOR:	Ilias Mylonis, Associate Professor of Biochemistry
CO-INSTRUCTORS:	G. Simos, P. Liakos, G. Chachami, T. Sideri,  A. Karagiota
ECTS:	5.00

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Type|Type of Course::YP | Background & Scientific Area

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Teaching Semester:1st Semester

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WEEKLY TEACHING HOURS:6 Hours

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Total Time (Teaching Hours + Student Workload)    149 Hours

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PREREQUIRED COURSES:  Νο

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LANGUAGE OF TEACHING AND EXAMS:  Greek

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AVAILABLE TO ERASMUS STUDENTS : Yes

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Semester Lectures:Details/Lectures

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Teaching Method:

Face to Face:

Teaching of Medical Chemistry consists of lectures, seminars/tutorials and laboratory practical.  Attendance of Laboratory Practical and Seminars/Tutorials is obligatory.

The lectures content is described above.

Seminars/Tutorials (in 4 student groups with 1 instructor per group) review and extend the theoretical background of laboratory exercises also by using examples of diagnostic methods that highlight the application of Medical Chemistry in the diagnosis and treatment of serious diseases.

Laboratory exercises (in 40 student groups of students, 3 instructors per group of 3 students) composing the students’ practical are complementary to the lectures and they aim to familiarize the student with the application of Medical Chemistry, the operation of simple laboratory instruments and the experimental procedures that are often used in biomedical research and laboratory medicine as well as to help the students comprehend concepts that are not easily presented theoretically (learning based on practical experience).

Attendance of Laboratory Practical and Seminars/Tutorials is obligatory.

Information and Communication Technologies are used for the preparation of the lecture material, the online information and provision of supplementary learning material to students.

Specifically:

• Common software (e.g. MS powerpoint) is used to prepare lecture material and display slides and videos.
• The study guide (detailed supplementary material & additional bibliography), the tutorial material (clinical cases), the theory and protocols of the laboratory exercises, the slides of each lecture as well as relevant videos and scientific articles made available electronically and online to students through the e-class system of our university.
• Information about the course, instructors and their research interests and in general the Laboratory of Biochemistry of the Faculty of Medicine are available online on the Laboratory website.
• Common software (e.g. MS excel) is used to statistically process student assessment.
• Laboratory examinations via the e-class platform.
• Announcements, information etc are available online via e-class. Communication is also done via e-mail.

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STUDENT EVALUATION

The language of assessment is English.

Evaluation methods.

A. For the laboratory practical: Laboratory Assignment Reports, Examination at the end of the semester with Online examination of the Laboratory Practical’s (Multiple choice test) via e-class & MS Teams platforms.

The participation of students in the laboratory exercises as well as the written report of the results of the exercises is mandatory. The report includes the results (presented in tables and diagrams, and the conclusions (e.g. if the results were expected, if not why, sources of possible errors in the experiments) as requested by each exercise. At the end of each exercise, the written report is checked by the instructors and signed when correctly completed. Successful participation in the practical is certified by the instructors’ signatures on the written reports. At the end of the semester the students are examined in the content of the Laboratory practical. The examined material consists of the theory, the methodology and the ways results are processed as included in the Guide of the Laboratory Practical or presented by the instructors during the exercises and seminars/tutorials. Only the students that have successfully completed the laboratory exercises can participate in the written laboratory examination. Success in the laboratory examination is a prerequisite for participation in the course exams.

B. For the lecture material: Written Exams with Multiple Choice, Short and Essay Development questions.

The course exams are written, last 2 hours and consist of Multiple Choice, Short and Essay Development questions (examples are available in the Course Guide). The material to be examined is lectures’ material as described above. Only those students who have successfully passed the Laboratory exams have the right to participate in the course exams.

Final Grade:

The final grade of the course is calculated as the sum of 80% of the grade of the written course exams and 20% of the grade of the Laboratory written exams. (Prerequisite: grade in final exam cannot be lower than 5/10).

All of the above are presented in detail in the Course Guide which is distributed in print to all students and is posted electronically in e-class.

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LEARNING OUTCOMES:

Aims of the course The course examines a selection of topics of general, physical, organic and biological chemistry that are important for living organisms, in general, and humans in particular. The course aims for the students to obtain the necessary background knowledge required for understanding the physiological and pathological functions of the human body at the molecular level and introducing the principles and techniques of laboratory methods commonly used for diagnosis. It also presents the application of Medical Chemistry knowledge in clinical settings such as the diagnosis and treatment of diseases. The course also provides the essential background for courses introduced at later semesters such as: Biochemistry, Physiology, Pharmacology and Clinical Biochemistry. Finally, another aim of the course is to help students appreciate the importance of correct execution and evaluation of laboratory methods and acquire the corresponding skills which are required for the specialty of Clinical Biochemistry as well as many other clinical medical specialties. After the successful completion of this course, the students will be able to: understand the chemical basis of biomedical phenomena. apply main aspects of laboratory analyses and evaluation of results. know the structure, properties and biological role of chemical elements and compounds found in the human body as well as the toxicity of xenobiotics. know the structure, properties, and role of fundamental biomolecules such as carbohydrates, lipids, amino acids, and proteins. use basic equipment of a Medical Chemistry lab and perform simple routine chemical analyses. analyze and process basic medical chemistry analysis results. cooperate with their colleagues in the context of a lab environment for the execution of simple medical chemistry analyses and processing of their results.

General Abilities

Research, analysis and synthesis of data and information, using the necessary technologies. Adaptation to new situations Decision making Autonomous work Teamwork Exercise criticism and self-criticism Promoting free, creative and inductive thinking

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URL Μαθήματος :https://eclass.uth.gr/courses/MED_U_169/

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Course Description:

The content of the course includes the following major items:

A. The content of the lectures together with the relevant clinical insights the students need to learn/acquire per chapter.

B. The content of the tutorials/seminars together with the relevant clinical insights the students need to learn/acquire per seminar.

C.The content of the laboratory practical together with the relevant practical & clinical skills the students need to learn/acquire per exercise.

A. Lecture content and relevant clinical insights

1: Periodic Table and Bioinorganic chemistry

• Periodic properties of elements and their relationship with atomic properties such as: ionization energy, electron affinity, electronegativity, size of atoms, size of ions, redox properties.
• Oxidation-reduction reactions, oxidation state, Oxidation-reduction in biological systems, membrane potential.
• Periodic table from a medical point of view: basic and trace elements of the human body. Toxic trace elements and examples of their effect on human health
• Vital elements and their selection by nature. Relevance of the biological role and chemical properties of the vital elements.
• Examples of the involvement of trace elements in pathological conditions.

2: Chemical bonding and non-covalent interactions

• Chemical bonds – Molecular orbitals. Sigma- and Pi- bonds.
• Hybridization of atomic orbitals and stereochemical structure of molecules.
• Types of dipoles and molecule polarity.
• Non-covalent interactions: Van der Waals forces, London, Hydrogen bonding. The role of non-covalent interactions in biomolecules.

3: Complex compounds and chelation therapy

• Complex or coordination compounds (Definition).
• Ligands and chelation complexes.
• Stability of chelation complexes (hard / soft acids and bases).
• Examples of complexes with biological significance.
• Chelation therapy applications. Complexing agents that find use in complex therapy and corresponding pharmaceutical preparations.

 4: Acid-Base equilibrium and buffers

• Properties of electrolytic solutions.
• Electrolytes of the extracellular and intracellular fluid.
• Lewis acid-bases.
• Blood pH and pH balance.
• Buffers, buffer capacity.
• Henderson-Hasselbalch equation and preparation of buffer solutions.
• Blood regulatory systems.
• Effects of CO₂, HCO^–₃ and H₂CO₃ on blood pH.

5: Dispersion systems

• Dispersion systems: mixtures, colloidal systems, solutions.
• Solution concentration and solubility, unsaturated, saturated and supersaturated solutions.
• Hydrophilic / hydrophobic / lipophilic chemical compounds and their relation to chemical structure. Hydrophilic functional groups.
• Additive properties of solutions: osmosis. Hypotonic, isotonic and hypertonic solutions. Plasmolysis and hemolysis.
• Colloid systems: aerosol, emulsion, suspension.
• Colloid systems in water: hydrophobic and hydrophilic colloids. Colloid thrombosis and its mechanisms.
• Increasing the water solubility of xenobiotics as means to detoxification.

 6: Introduction to organic chemistry

• Distribution of electron cloud in molecules: Inductive (I) and conjugate (delocalization) (R) effect. Resonance.
• Classification of reactions and reagents in organic chemistry. Nucleophilic and electrophilic reagents, free radicals.
• Reactive oxygen compounds, oxidative stress and human health.
• Functional groups of organic compounds and their role in the design of new drugs.

7: Stereochemistry of organic compounds

• Stereochemistry and stereoisomerism.
• Mirror image isomers / enantiomers
• Chiral/achiral compounds
• Asymmetric (chiral) center
• Optical activity, (+) – right-handed and (-) – left-handed enantiomer.
• Racemic mixture, racemization.
• Fischer projection
• Absolute stereochemical structure D,L symbolism.
• Stereoisomerism of chiral centers according to the CHAN-INGOLD-PRELOG rules and R-S symbolism.
• Diastereomerism, meso-isoform.
• Geometric isomerism: CIS – TRANS, Z-E, priority of ligands.
• Nucleophilic substitution reactions SN1, SN2.

 8: Hydrocarbons and Aromatic Compounds

• General properties and reactions of hydrocarbons. Electrophilic addition reactions, hydrogenation, hydration of unsaturated hydrocarbons.
• Aromatic hydrocarbons: aromatic character, HUCKEL’s rule. Electrophilic substitution – characteristic reaction of aromatic hydrocarbons.
• Resonance energy, aromatic stabilization.
• Examples of hydrocarbons in biological systems.

9: Oxygen, Sulfur, and Nitrogen containing compounds

• Alcohols: properties (water solubility, acidity), production (by reduction of aldehydes, ketones, by hydration of alkenes), reactions (oxidation, dehydration, esterification, nucleophilic substitution).
• Phenols: Properties: water solubility, acidity
• Thiols: properties (water solubility, acidity), reactions, disulfide bond and its biological importance.
• Sulfonic acids and derivatives of 4-aminobenzenesulfonic acid – the sulfonamide drugs.
• Aliphatic amines: primary, secondary, tertiary. General properties. Characteristic reactions.
• Aromatic amines: general properties and their comparison with aliphatic amines.
• Aliphatic quaternary ammonium salts.
• Amides, Imines, Amino-alcohols.

10: Carbonyl- and Carboxyl- compounds

• Carbonyl compounds: properties, polarity, electrophilic and nucleophilic attack, Enol-ketone tautomerization, tautomers.
• Nucleophilic addition reactions. Hemiacetals, hemiketals, acetals, ketals. Condensation with amines (R-NH₂). Imines – Schiff’s bases.
• Aldol condensation.
• Ketoacids, urinary ketones, ketoacidosis. Causes of ketoacidosis and ketonuria.
• General properties of carboxyl group: ionization, coordination.
• Acyl derivatives of acids.
• Formation and hydrolysis of carboxylic acid esters.
• Dicarboxylic acids, hydroxy acids, ketone acids and unsaturated acids: Special properties and members of biological interest.

 11: Heterocyclic compounds

• Definition of heterocyclic compounds.
• Five-membered ring heterocyclic compounds with one heteroatom and their derivatives: pyrrole (proline, porphyrin), imidazole (histidine), thiophene (biotin). Chemical properties: aromaticity, participation in nucleophilic or electrophilic substitution reactions, acid-base properties.
• Five-membered heterocyclic compounds with two heteroatoms: imidazole and its derivatives histidine and histamine, thiazole (thiamine – vitamin B1).
• Six-membered ring heterocyclic compounds with one heteroatom and their derivatives: pyridine (NAD+ , NADP+ , pyridoxal). Chemical properties of pyridine: aromaticity, participation in nucleophilic or electrophilic substitution reactions, acid-base properties.
• Six-membered ring heterocyclic compounds with two heteroatoms and their pyrimidine derivatives (uracil, thymine, cytosine).
• Condensed heterocyclic rings and their derivatives: indole (tryptophan), purine (adenine, guanine), isoalloxazine (riboflavin, FAD, FMN), pteridine (folic acid).
• Structure and properties of nucleosides and nucleotides.

12: Structure and biological role of amino acids

• Biological functions of amino acids.
• Common chemical structure, stereochemistry, common chemical properties, and ionization of amino acids.
• Chemical structure of the 20 proteinogenic amino acids: Hydrophobic, Polar, Charged.
• Essential Amino Acids, Amino Acid Modifications & Derivatives.
• Spectroscopic properties and biologically important reactions.
• Detection & analysis.
• Peptides & peptide bond, important peptides.

 13: Structure and biological role of proteins.

• General properties of proteins
• Molecular interactions determining protein structure and function
• Levels of molecular organization
• Primary structure
• Physicochemical properties – Solubility
• 3D Structure – Limitations
• Secondary structure: α-helix, β-fold, turns & loops
• Tertiary structure

The role of hydrophobic interactions

The example of myoglobin

The role of disulfide bonds

• Quaternary structure
• Protein structure representation
• Experimental determination of protein structure
• Protein folding

Anfinsen’s experiment

The role of amino acids, Cumulative selection, Molecular chaperones

Models and computational methods

Intrinsically disordered and metamorphic proteins

Fatal errors: Amyloidosis, encephalopathies, prion diseases

 14: Structure and biological role of carbohydrates and lipids

• Basic chemical structure, functions, classes and stereo-isomerism of carbohydrates
• Common monosaccharides:

Circular structures & mutarotation

Reducing sugars, Glycated hemoglobin

Hexose derivatives

• Glycosidic bond
• Common disaccharides
• Polysaccharides: Starch/Glycogen, Cellulose, Chitin
• Glycoproteins, Proteoglycans, Glycosaminoglycans, Glycolipids
• Biological role & Classes of lipids
• Fatty acids: Chemical structure, properties, Nomenclature
• Triacylglycerols: Chemical structure, properties
• Phospholipids: Chemical structure, properties of Phosphoglycerates & Sphingolipids
• Glycolipids and ether lipids
• Steroids: Cholesterol & derivatives, Vitamin D
• Separation and analysis of lipids

15: Thermodynamics and Chemical Equilibrium

• Chemical thermodynamics principles
• Enthalpy, entropy, and free energy of chemical & biochemical reactions. Work and free energy. Standard free energy. Exothermic / endothermic reaction. Exergonic / endergonic reactions
• Equilibrium constant of a reaction. Factors affecting the equilibrium constant – VAN’T HOFF equation.
• Free energy and equilibrium constant ΔG^o = – RT ln Keq
• HESS’s law, LE CHATELIER’s principle.
• Coupling of chemical and biochemical reactions, the role of chemical intermediates.
• Experimental determination of enthalpy, entropy and free energy

16: Chemical kinetics and reaction mechanisms

• Rate of chemical reactions, rate law, order of reaction.
• Zero, first and second order reactions and their mathematical description with differential or integral equations. Half-life time and dependence on concentration.
• Molecularity of chemical reactions.
• Theory of molecular collisions. Activation energy of a reaction. Arrhenius equation. Examples of nucleophilic – electrophilic reactions.

17: Introduction to enzymes

• General characteristics, clinical applications, function and enzyme cofactors
• Classification & Nomenclature of Enzymes
• Thermodynamics & Transition state of enzyme reactions
• Enzyme Active Site: Characteristics, Models, Binding Energy

18. Εnzyme kinetics

• The steady state model in enzyme kinetics
• The Michaelis-Menten equation
• The significance of V_max, K_M and the Michaelis-Menten curve
• Vmax and K_M values, turnover number, specificity constant
• Experimental determination of V_max and K_M
• Double inverse chart
• Physiological Significance of V_max and K_M:

Alcohol Sensitivity, Glucose Fate, Laboratory Diagnosis, Drugs and poisons

19: Enzyme regulation

• Basic principles of enzyme activity regulation
• Allosteric regulation:

Characteristics of allosteric enzymes

V vs [S] sigmoid curve, Two configurations (R and T), Models

Allosteric modifiers

Synergistic properties

Feedback inhibition

Catalytic/Regulatory subunits

• Isoenzymes
• Regulation by covalent modifications
• Proteolytic cleavage – Zymogens

20: Catalytic mechanisms of enzymes and enzyme inhibitors

• Basic principles of catalysis

Covalent, General acid-base, metal ion, by approximation and orientation

pH and temperature effects

• Enzyme inhibitors

Types of inhibition and kinetic differences

Inhibitors as tools to study enzymes

Inhibitors as drugs

• Catalytic strategies of serine proteases

Chymotrypsin, Trypsin, Elastase

Specificity, Role of active center serine, Catalytic triad

Tetrahedral transition state

• Catalysis strategies of other proteases
• High speed enzymes: Carbonic anhydrases
• Enzymes with high specificity: Restriction endonucleases

 

B. Seminar/Τutorial content and relevant clinical insights

Tutorial 1: Chemical Analysis

• Theoretical background of UV-Vis spectrometry (Lambert-Beer Law, UV-Vis quantitative analysis), standard solutions, equipment calibration and calibration curves.
• Theoretical background of chromatography, methodology, examples
• Analysis and interpretation of experimental data, troubleshooting.

Tutorial 2: Methods of Protein analysis

• Theoretical background of protein isolation, purification, and analysis: centrifugation, fractionation, dialysis, chromatography, methods of electrophoresis, mass spectrometry
• Electrophoresis: Background and examples of diagnostic value
• Protein analysis (sequencing, immunodetection, microscopy)

Seminars:

• Revision of Theoretical / Practical Courses

 

C. Laboratory Practical content

Hands-on learning: Acquisition of general and specific practical & clinical skills:

General Skills

Observing chemical or biochemical phenomena, obtaining, and analyzing experimental data

Interpretation of experimental data

Resolving practical problems

Producing and understanding graphical displays of data

Operating basic Chemistry & Biochemistry equipment

Working as a team

Following instructions

Following safety regulations

Troubleshooting in laboratory results

Clinical significance of lab results

Specific Skills

Practical 1. Spectrophotometry UV-Vis

Spectrophotometric detection and analyte quantitation

Practical 2. Buffer systems and titration

Measuring the concentration of analytes via titration and preparation and pH measurement of a buffer system

Practical 3. Chromatographic analysis of amino acids and proteins

Separation and analysis of protein and amino acid samples by chromatography

Practical 4. Electrophoresis and analysis of protein samples

Analysis of a protein sample by SDS-PAGE electrophoresis, effect of pH and temperature on protein solubility

 

Recommended Bibliography :

Α. Lecture Material

Main suggested textbooks:

– Slides from Lectures (e-class)

– Biochemistry, A Short Course (Tymoczko, Berg, Stryer, 3^rd edition)

– Chemistry: An Introduction to General, Organic, and Biological Chemistry (Karen Timberlake, 13^th edition)

– Physical Chemistry for the Chemical and Biological Sciences (Raymond Chang, by University Science Books)

– Organic Chemistry for Students of Biology and Medicine (G. A. Taylor, by Giles Aldred)

Β. Laboratory Practical supplementary Material

Course Guide for Medical Chemistry