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Biochemistry - DA0103446
Title: Biochemistry
Guaranteed by: Department of Medical Chemistry and Clinical Biochemistry (13-352)
Faculty: Second Faculty of Medicine
Actual: from 2022
Semester: winter
Points: 12
E-Credits: 12
Examination process: winter s.:
summer s.:
Hours per week, examination: winter s.:4/4, C [HT]
summer s.:4/4, C+Ex [HT]
Extent per academic year: 14 [weeks]
Capacity: winter:unknown / unknown (unknown)
summer:unknown / unknown (unknown)
Min. number of students: unlimited
4EU+: no
Virtual mobility / capacity: no
Key competences:  
State of the course: taught
Language: English
Teaching methods: full-time
Level:  
Guarantor: prof. MUDr. Richard Průša, CSc.
Classification: Medicine > Basic Sciences
Co-requisite : DA0103337
Pre-requisite : DA01010332
Is co-requisite for: DA0103337
Is pre-requisite for: DA0105340, DA0105439, DA0107363, DA0105341
Course completion requirements

The exam consists of a written test and an oral examination. Passing the test is a prerequisite for the oral examination.

Last update: Kohutiar Matej, MUDr., Ph.D. (29.09.2019)
Literature

M.Lieberman,A.D.Marks: Mark’s Basic Medical Biochemistry 2017

R.K.Murray et al.: Harper's Illustrated Biochemistry :twenty-sixth edition, McGraw-Hill, 2003

J.Koolman K.H.Roehm: Color atlas of biochemistry, 2005

Presentations of the Department in Moodle.

Last update: Kohutiar Matej, MUDr., Ph.D. (10.06.2021)
Requirements to the exam

Winter and summer credit.

Credit conditions:

1. Participation in seminars and practical trainings.

2. Successful completion of 2 interim tests in winter and 1 in summer semester.

Students, who has successfully passed interim/summary tests and met the attendance conditions, will get the credit. The summer semester credit has to be preceded by the winter semester credit. Student cannot enroll for the exam without both credits.

Last update: Kohutiar Matej, MUDr., Ph.D. (29.09.2019)
Syllabus

BASIC BIOCHEMSITRY AND METABOLISM

Basic and physical chemistry

Chemical bond. Disperse systems and osmosis. Chemical equilibrium – acid base balance, precipitation and complex balance. Medical chemistry calculation. The International System of Units (SI). Conversions of multiples and fractions of units. Composition of mixtures: mass and volume ratio. Dilution. Mass concentration. Calculation of pH of solutions of strong acids and bases. Osmolarity and osmolality.

Basic biochemistry

Basic bioorganic chemistry. Structures of organic compounds. Basic types of organic reactions. Organic compounds containing oxygen, nitrogen and sulphur.

Intermediary metabolism.

Anabolic, amphibolic and catabolic reactions, metabolic turnover. Overview of metabolism.

Introduction to membranology

Structure, composition and properties of biological membranes. Membrane transport.

Enzymology

Mechanisms of enzyme catalysis. Structure and function of enzymes. Thermodynamic aspects of enzyme catalysis. Mechanisms of enzyme catalysis and its regulation. Classification of enzymes. Importance of enzymes in medicine. Enzymopathies. Kinetics of enzyme reactions. Chemical kinetics. Kinetic characterisation of enzymes, Michaelis-Menten equation. Types and mechanisms of enzyme inhibition. Cofactors. Coenzymes and prosthetic groups. Importance of the cofactor for the enzyme reaction course.

Bioenergetics

Bioenergetics. Basic terms of thermodynamics. First and second laws of thermodynamics. Enthropy. Gibbs energy. ATP and nother macroergic (high-energy) compounds . Oxidative phosphorylation and mitochondrial transport systems. ATP functions in preservation and transformation of chemical energy, electron transport chain and the Mitchell chemiosmotic theory, synthesis of ATP. Citrate cycle. The central role of citrate cycle in the intermediary metabolism, production of reduced cofactors. Anaplerotic reactions.

Carbohydrate metabolism

Carbohydrates. Structure, function and properties of carbohydrates. Glycolysis. Anaerobic and aerobic mechanisms of glucose degradation, connections with other metabolic pathways, regulation of glycolysis and its crucial enzymes. Gluconeogenesis. Mechanisms of glucose de novo synthesis, substrates of gluconeogenesis, compartmentation and regulation of gluconeogenesis. Cori cycle. Glycogen. Glycogen metabolism, regulation of its biosynthesis and degradation. Liver and muscle glycogen. Glycogen metabolic disorders. Pentose phosphate pathway. Pentose phosphate pathway importance for the metabolism of a cell, NADPH production and its utilisation in reductive syntheses. Mutual conversions of monosaccharides. Metabolism of fructose and galactose, entry points of monosaccharides to the metabolism. Enzymatic disorders of fructose and galactose metabolism. Regulation of the saccharide metabolism. Interconnection of saccharide metabolic pathways, types of regulations, crucial enzymes. Principles of hormonal regulation in saccharide metabolism: insulin and glucagon.

Lipid metabolism

Lipids. Structure, function and properties of fatty acids and other lipids. Biosynthesis and degradation of fatty acids. Biosynthesis of fatty acids, elongases, desaturases. β-Oxidation of fatty acids in mitochondria and peroxisomes. β-Oxidation energy yield. Metabolism of glycerolipids and sphingolipids. Synthesis and degradation of acylglycerols and sphingolipids. Metabolic disorders. Cholesterol and its transport. Biosynthesis and degradation of cholesterol, cholesterol transport, lipoprotein complexes and their metabolism, cholesterol utilisation for other syntheses, cholesterol degradation. Disorders of cholesterol metabolism. Regulation of lipid metabolism. Interconnection of lipid metabolic pathways, types of regulation, crucial enzymes. Principles of hormonal regulation in lipid metabolism.

Metabolism of proteins and nitrogen containing compounds.

Proteins.

Structure, function and properties of amino acids and proteins. Metabolism of amino acids. Synthesis and degradation of amino acids. Inter-tissue transport of nitrogen, role of liver in ammonia detoxication. Glucogenic and ketogenic amino acids. Selected disorders of amino acid metabolism. Urea cycle. Urea cycle and its importance. Intermediates of the urea cycle and their fate in metabolism. Transaminases. Disorders of urea cycle. Conversions of amino acids to special products. Amino acids as substrates for synthesis of hormones and other biologically active substances (neurotransmitters, creatine, S-adenosylmethionine). Biosynthesis and degradation of proteins. Role of the ribosome, initiation, elongation and termination phases of proteosynthesis. Proteases and proteasome. Nucleic acids and nucleotides. Structure, function and properties of nucleic acids and nucleotides.

Metabolism of nucleotides.

Synthesis and degradation of purine and pyrimidine nucleotides, regulation of nucleotide metabolism. Uric acid and hyperuricemia. Porphyrins and bile pigments. Synthesis and degradation of haeme, bile pigments. Porphyrias.

Minerals and a vitamins

Minerals and trace elements. Biologically important minerals and trace elements, their occurence in biological structures and contribution to regulation of metabolic processes. Metabolism of iodine, calcium, phosphate and selenium. Vitamins. Structure and function of vitamins. Water and fat soluble vitamins. Metabolism of selected vitamins (folic acid, cobalamine, vitamin D, vitamin A, vitamin C, vitamin E a vitamin K). Metabolism of iron. Mechanisms of vitamin absorption and recycling, their regulation and relationships to pathologies.

Cell signalling

Mechanisms of signal transduction into the cell. Mechanisms of signal transduction into the cell, G-protein coupled receptors, ion-channel coupled receptors, receptors with enzyme activity, intracellular receptors. Intracellular signalling by calcium. Calcium importance for signal transduction, calcium-binding proteins and calcium signalling pathways.

Special subjects

Glycoproteins and mucins, structure, sugar components, biological functions. Chemical composition and main types of mucins, their role in biological processes. Metabolism of eicosanoids. Metabolism of arachidonic acid. Cyclooxygenase and lipooxygenase pathways. Subcellular compartmentation and metabolism integration. Intracellular organelles as sites of specific metabolic pathways. Interconnections of metabolic pathways. AMP- activated protein kinase.

FUNCTIONAL AND ORGAN-LEVEL BIOCHEMISTRY

Blood

Proteins of the blood plasma. Sorting of blood plasma proteins. Biological importance of selected proteins, electrophoresis of blood plasma proteins. Acute phase reactants (CRP and others), sedimentation. Metabolism of erythrocytes. Metabolism of erythrocytes, types of haemoglobin: phoetal haemoglobin, pathological forms. Erythrocyte membrane. Cooperative kinetics and oxygen saturation of haemoglobin. Transport of blood gasses and the Bohr effect. Haemoglobinopathies and methemoglobinemia.

Biochemistry of immune system and of inflammation.

Chemical structure of antigens. MHC glycoproteins of the classes I. and II. The complement. Metabolism of granulocytes and thrombocytes. NADPH oxidase and respiratory burst. Composition of the lymph. Immunoglobulins and immunochemical reactions. Types of immunoglobulins and structure of antibodies, the antigen-antibody binding, monoclonal and polyclonal antibodies. Employing the antigen-antibody interaction for analytical purposes. Immunochemical methods.

Biochemistry of the muscle.

Contractile apparatus and muscle contraction. Energy substrates (fuels) for the muscle function. Rigor mortis. Basic biochemical markers of muscle injury.

Biochemistry of the heart and blood vessels.

Energy metabolism of myocardium. Energy metabolism of dysfunctional myocardium. Ischemic injury and its diagnostics, cardial markers (ANP, BNP, troponins). Metabolism of nitric oxide.

Biochemistry of the lungs and heart.

Lung biochemistry, chemical composition of the surfactant and its functions, effects of oxygen concentration changes on the tissues. Lungs as an organ of special metabolic pathways.Atherosclerosis. Pathobiochemical mechanisms of atherosclerosis development.

Endocrinology

Biochemistry of peptidic and amino-acid based hormones. Principles of hormonal signalling. Biosynthesis and degradation of peptidic and amino-acid based hormones. Selected hormones and their effects. Biochemistry of steroid hormones. Basic mechanisms of steroid hormone biosynthesis, individual types of steroid hormones, main metabolic pathways regulated by steroid hormones. Biochemical aspects of gravidity and lactation. Maternal milk composition. Biochemistry of thyroid hormones. Thyroid hormone biosynthesis and its regulation, metabolic conversions of thyroid hormones, biological processes regulated by thyroid hormones. Pathobiochemistry of diabetes. Effects of insulin, glucagon, glucocorticoids, catecholamines and growth hormone on the blood sugar level. Overview of metabolic changes and pathological processes elicited by diabetes at the molecular level – protein glycation. Glycated haemoglobin. OGTT.

Biochemistry of adipose tissue.

Adipose tissue as an endocrine organ. Metabolic processes taking place in the adipose tissue. Role of the brown adipose tissue, mechanism of heat production at the mitochondrial level, function of uncoupling proteins. Hormones of the adipose tissue. PPAR.

Connective tissue.

Proteins of the extracellular matrix.

Role of collagen, elastin and other proteins in the extracellular matrix function, their synthesis and degradation, protease inhibitors, matrix metalloproteinases. Biochemistry of the bone and tooth. Chemical composition of the bone and tooth, role of osteoblasts and osteoclasts in the bone metabolism, hormonal regulation of calcium metabolism. Markers of bone formation and degradation.

Biochemistry of the skin.

Composition and function of skin, formation and composition of sweat, biosynthesis of melanins.

Kidneys and the internal environment.

Kidney biochemistry. Kidneys as a site of special metabolic processes, renin-angiotensin-aldosterone system. Basic biochemical indicators of renasl function (clearance). Urine and urinary sediment. Physiological and pathological urine components. Organic and non-organic components of the urinary sedimentu. Urinary stones. Acid-base balance and the internal environment. Biological buffers (definition, composition, buffering capacity, titration curve), Henderson-Hasselbalch equation. Alkalosis and acidosis. Roles of the lungs, kidneys and the liver in maintaining the acid-base balance of the body. Examination according to Astrup.

Digestive tract.

Biochemistry of the digestive tract. Biochemical processes participating in nutrient digestion. Absorption and metabolism of saccharides, proteins, fats, vitamins and trace elements. Enterohepatic circulation. Incretins. Liver biochemistry. Overview of metabolic pathways taking place in the liver, liver as a regulatory site of biological processes of the body. Hyperbilirubinaemia and icterus. Bile concrements. Basic biochemical markers of hepatic functions. Biotransformation reactions. Detoxication of metabolic end-products, biotransformation of xenobiotics. Genotypes of biotransformation enzymes.

Biochemistry of nutrition.

Biochemistry of nutrition. Macronutrients and micronutrients. Usage and interorgan exchange of energy substrates.

Nervous system.

Biochemistry of CNS and neurotransmitters. Metabolism of nervous tissue. Synthesis and inactivation of catecholamines and serotonine. Glutamic acid, aspartic acid and glycine – their roles as mediators. Acetylcholine, effect on post-synaptic receptors and its inactivation. Inhibitors of acetylcholine esterase. The liquor composition. Biochemistry of the senses. Biochemistry of vision – mechanism of photon capture and conversion to a chemical signal. Role of vitamin A and its metabolites in the process of vision. Biochemical nature of the olfactory and gustatory perception.

Cellular damage.

Basics of medical toxicology. Dose dependence of the effect. Toxicity scale. General mechanisms of toxicity. Organic toxicity. Toxic effects of selected substances. Biochemistry of oxidative stress. Reactive oxygen species and free radicals, cellular damage and antioxidative defence. Importance in medicine. Damage and death of the cell. Pathobiochemical aspects of cellular damage and death. Influence of reactive oxygen species, disorders of calcium homeostasis, lack of ATP, cell membrane deffect. Aging.

Laboratory medicine.

Basic principles of the laboratory medicine. Selected panels of biochemical tests. Sporadically examinated materials (BAL, transudate, exudate, stools, pleural effusion, aspirate, synovial fluid). Pre-analytical, analytical and post-analytical phase. Reference intervals, intra- and inter-individual variability. Reference intervals of selected analytes. Screening of genetically linked metabolic disorders.

PRACTICAL EXERCISES

Basic laboratory techniques.

Sampling and processing of biological material. Weighing and measuring liquids. Solution preparing. Elemental equipment of chemical laboratory. Laboratory safety rules.

First aid instructions.

Analytical methods.

Methods of qualitative analysis- calibration curve. Volumetric analysis, spectroscopy, chromatography, electrophoresis, potentiometry, mass spectroscopy.

Volumetric analysis.

Acid-base titration, determination of equivalence point, result calculation.

Enzymatic kinetics.

Lactate dehydrogenase isolation from biological material and determination of Michaelis constant of lactate.

Analysis of the selected parameters of lipid metabolism.

Total, HDL and LDL cholesterol determination of sample by spectroscopy. Lipoprotein electrophoresis.

Identification and determination of amino acids.

Potenciometric titration of amino acids, analysis of titration curve. Thin-layer chromatography of amino acids.

Basic principles of immunochemical methods.

Blood group determination and C-reactive protein analysis. ELISA (demonstration).

Electrophoresis of blood plasma proteins.

Quantitative analysis of proteins by selected methods. Electrophoresis of blood plasma proteins. Electropherogram interpretation.

Biochemical examination of liver functions and ethanol metabolism.

Determinative principles of selected analytes (AST, ALT, GMT, ALP). Confirmation the presence of ethanol in breath.

Analysis of urine and urine sediment.

Measurement of endogenous creatinine clearance. Physical analysis of urine. Fyzikální vyšetření moči. Chemical analysis of urine using diagnostic strips. Chemical analysis of urine in solutions (proteins, reducing sugars, ketone bodies, blood, urobilinogen). Urine sediment analysis. Demonstration of urinary concrements (collection and polarization microscopy).

Buffer capacity and examination of acid-base balance.

Determination of buffer capacity of phosphate buffer by potenciometric titration. Assessment of acid-base balance according to Astrup.

Oral glucose tolerance test (OGTT).

Performing and interpretation of OGTT. Result comparison of results with determinate plasmatic glucose by photometrical estimation and with determination of glucose by glucometer.

Last update: Kohutiar Matej, MUDr., Ph.D. (29.09.2019)
 
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