Syllabus
1. Introduction to biochemistry Biochemistry within the system of biological, chemical and medical sciences. The role of biochemistry in contemporary medicine and its perspectives.
2. Properties of peptides and proteins Amino acids, their properties, and their classification according to the polarity of their side chains and according to the acid-base properties. Essential and non-essential amino acids. Structure of peptides and proteins, their primary structure. Structures of higher order and their meaning for the function of peptides and proteins.
3. Enzymes Basic characteristics of enzymes and basic enzyme properties. Substrate and reaction specificity of enzymes. Enzymes as proteins. Apoenzymes and coenzymes. Active sites of enzymes. Mechanisms of catalytic activity, examples. Thermodynamic and catalytic aspects of enzymatic catalysis. Velocity of enzymatic reaction, Michaelis´ constant and its practical meaning. Inhibition of enzymatic reactions. Competitive and non-competitive inhibitors. Allosteric enzymes and allosteric inhibiton and activation and their importance in metabolism. Isoenzymes - relationship to the organization of genes, their importance for the metabolic regulations and for the diagnosis in medicine. Classification and nomenclature of enzymes.
4. Bioenergetics and the role of high energy compounds Chemical reactions as thermodynamic processes. First and second low of thermodynamics. Enthalpy, free energy, entropy. Endothermic and exothermic reactions. Entropy and living systems. Conservation and transfer of energy in living systems, high energy compounds, ATP.
5. Redox reactions as a source of energy Oxidation and reduction. Redox potential and standard redox potential. Thermodynamics of electron transfer. Redox reactions as a main source of energy in aerobic organisms.
6. The respiratory chain and oxidative phosphorylation Mitochondria and its structure. Dehydrogenases and their function. Coenzymes NAD, NADP, FMN, and FAD. NADH dehydrogenase, coenzyme Q, cytochrome system. Cytochrome c reductase and cytochrome c oxidase. Organisation of the respiratory chain, transfer of electrons and transfer of protons. Formation of proton gradient and its usage. ATP synthesis as a function of proton gradient. Stoichiometry of dehydrogenation and formation of ATP. Proton gradient and formation of heat. Inhibitors of the respiratory chain, their experimental and medical importance.
7. The citrate cycle Structure of CoA, its formation and function. Acetyl-CoA. Description of individual reactions of the citrate cycle. Dehydrogenation steps in citrate cycle and their connection with the respiratory chain. Energy output of the citrate cycle. Regulation of the citrate cycle at the individual enzyme level. Amphibolic character of the citrate cycle - the need for the supplementing (anaplerotic) reactions - pyruvate carboxylase. Mechanism of carboxylation, the role of biotin.
8. Glycolysis Description of individual glycolytic reactions and glycolytic enzymes. Glycolysis in aerobic and in anaerobic conditions. Formation of lactate. Relationship between glyceraldehydephosphate dehydrogenase and lactate dehydrogenase and its importance. Energy production in glycolysis under aerobic and anaerobic conditions. Regulation of glycolysis - importance of phosphofructokinase and fructose-2,6-bisphosphate. Activation of feed-forward type.
9. Metabolism of pyruvate Anaerobic conversion into lactate and its importance. Alcoholic fermentation. Carboxylation of pyruvate into oxaloacetate. Oxidative decarboxylation of pyruvate into acetyl-CoA. Total energy production of glucose metabolism under different conditions. Compartmentation of individual processes in the cell, connection of extra- and intramitochondrial redox processes, malate shunt and glycerolphosphate shunt.
10. Gluconeogenesis Description of individual steps in gluconeogenesis, relation to the glycolysis. Non-reversible reactions of glycolysis and their specific solution in gluconeogenesis. Cycling of some reactions and its meaning. Regulation of gluconeogenesis in connection with regulation of glycolysis.
11. Synthesis and degradation of glycogen Structure of glycogen, reducing end non-reducing ends of the molecule. The role of glycogen in the energy producing metabolism. Degradation of glycogen. Phosphorylase, mechanism of activity, its regulation. cAMP cascade. Debranching enzyme, its transferase and glucosidase activity. UDP-glucose. Gycogen synthase and branching enzyme. The overall regulation of glycogen metabolism. Control of blood glucose.
12. The pentose phosphate pathway Description of individual steps of pentose cycle. Importance of glucose-6-phoshpate dehydrogenase for production of NADPH, reduced glutathion and degradation of peroxides. Formation of pentoses and their significance. Transaldolase and transketolase. Relationship between the pentose cycle and glycolysis. The role of pentose cycle in photosynthesis. Brief description of photosynthesis as a basic process in autotrophic organisms.
13. Metabolism of other saccharides Carbohydrates as nutrients. Digestion of starch and glucose resorption. Digestion of sucrose, utilisation of fructose and its problems. Conversion of glucose to galactose, biosynthesis of lactose. Digestion of lactose, utilisation of galactose and its disorders.
14. Metabolism of fatty acids Fatty acids in energy-producing metabolism. Activation of fatty acids - acyladenylates and acyl-CoA. Transport of activated fatty acids into mitochondrial matrix, acyl-carnitine. Beta-oxidation of fatty acids, production of acetyl-CoA. Energy output of fatty acid oxidation. Comparison with carbohydrates with respect to the oxygen consumption and energy production. Degradation of fatty acids in mitochondria and in peroxisomes. Biosynthesis of fatty acids. Transfer of substance and reducing potential for this synthesis from mitochondria into cytosol. Formation of malonyl-CoA and its regulation. Importance of ACP (acyl-carrying protein) and its role in fatty acid synthesis. The regulation of fatty acid synthesis and degradation.
15. Ketone bodies. Relations between the carbohydrate and fatty acid metabolism Conversion of acetyl-CoA into 3-hydroxy-3-methyl-glutaryl-CoA (HMG). Formation of acetoacetate and other ketone bodies. Ketone bodies as water-soluble equivalent of fatty acids. Utilisation of ketone bodies in different tissues. Ketone bodies in starvation. Equilibrium of ketone bodies formation and utilisation. Conversion of carbohydrates into fatty acids and triacylglycerols, impossibility to convert fatty acids into carbohydrates. Explanation of this phenomenon. Metabolic disorders related to the preferential utilization of fatty acids, starvation, diabetes mellitus. Ketone bodies as indicators of metabolic disorder, ketoacidosis.
16. Triacylglycerols in metabolism Triacylglycerols (TAG) as energy storage molecules. Their biosynthesis and degradation. TAG in nutrition. Digestion and resorption of TAG. Resynthesis of TAG in enterocytes and formation of chylomicrons. (VLDL). Lipoprotein lipase. Utilisation pf fatty acids in different tissues, utilisation in adipocytes. The dynamic equilibrium (steady state) of stored TAG in adipocytes. The absence of glycerol kinase in adipose tissue and its significance. Blood glucose level and TAG in adipocytes. Hormone-sensitive lipase and its regulation. Mobilisation of fat in adipose tissue. Free fatty acids (FFA) in blood and their transport on albumin.
17. Metabolism of cholesterol Biosynthesis of cholesterol. HMG reductase as the checkpoint of cholesterol synthesis and target of therapeutic action. The role of cholesterol in organism and the role of the liver in cholesterol metabolism. Degradation and excretion of cholesterol. Primary and secondary bile acids and their importance, their enterohepatic circulation. The excretion of bile acids, the influence of dietary fiber and therapeutic agents.
18. Lipoproteins of blood plasma Digestion and resorption of lipids. Formation of chylomicrons, their circulation and degradation with lipoprotein lipase. Fianl degradation of chylomicrons remnant in the liver. Formation of VLDL in the liver, circulation, degradation and conversion to LDL. The role of LDL and LDL receptors. Reverse transport of cholesterol, HDL. The role of individual apoproteins, their biological significance. The risk factors of atherosclerosis. The examination of lipoproteins, hyperlipoproteinemias.
19. Steroid hormones and vitamins D Vitamin D and its conversion to calcitriol. Biosynthesis of individual groups of steroid hormones, their significance in organism. Degradation of steroid hormones and the estimation of degradation products in body fluids.
20. Metabolism of acylglycerols and sphingolipids Biosynthesis of diacylglycerol phosphate (phosphatidate), activation to CDP-derivative, formation of phosphatidylserine, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol-4,5-bisphosphate. Cardiolipins, ether phospholipids, plasmalogens, PAF. Phospholipases, their role in degradation and in production of regulatory molecules - diacylglycerol and inositol trisphosphate. Biosynthesis of sphingosine, ceramide and sphingolipids - sphingomyelins, cerebrosides, sulfatides, and gangliosides. Degradation of sphingolipid
Annotation
Amino acids and proteins. Enzymes. Thermodynamics of bichemical events. Respiratory chain and energy formation. Citrate cycle. Glycolysis. Conversions of pyruvate. Pentose phosphate pathway. Gluconeogenesis. UDP derivatives of carbohydrates, metabolism of glycogen. Metabolism of galactose and fructose. Metabolism of lipids, oxidation ans biosynthesis of fatty acids. Laboratory methods in biochemistry.
Metabolism of membrane lipids, lipoproteins, steroids. Metabolism of amino acids. Nucleotides, chemistry and biology of nucleic acids. Molecular diseases, DNA diagnostics. Porphyrins, hemoglobin, plasmatic proteins. Biochemistry of connective tissue, bone and teeth. Biochemistry of liver, kidney, muscles and brain. Xenobiochemistry. Foundations of laboratory enzymology, clinical biochemistry and examination of body fluids.