Syllabus
(1) "Inborn Errors of Metabolism" by Archibald Garrod. Transport defects of amino acids. Hyperoxaluria. Disorders of aromatic amino acids. Molecular mechanism of phenylketonuria (PKU). Pathogenesis, diagnosis and treatment of PKU.(2) Catabolism of purine nucleotides. Metabolic pool of uric acid, excretion of urates. Hyperuricaemia and gout. Feed-back control of purine synthesis and Lesh-Nyhan syndrome. Severe Combined Immunodeficiency Disease (SCID) and the gene therapy. Heme biosynthesis and porphyrias.(3) Composition of connective tissues. Elastin and collagen structure. Types of collagen. Biosynthesis of collagen molecules and their assembly to collagen fibers. Molecular basis of osteogenesis imperfecta and Ehlers-Danlos syndrome. Homocystinuria.(4) Intracellular degradation of proteins and autophagy. Proteolytic systems. Homeostatic role of peptidases and their inhibitors. Alpha-1-protease inhibitor. Molecular basis of the serpin inhibitory effect. Helix-sheet transition in serpins and prions. Conception of prion diseases.(5) Carbohydrate metabolism and its regulation. Lactic acidosis. Inborn errors of carbohydrate metabolism: Galactosemia, fructosuria, hereditary fructose intolerance, glycogenoses, pentosuria, glucose-6-phosphate dehydrogenase deficiency, transketolase mutation.(6) Diabetes mellitus type I and type II. Biochemical characterization of diabetes mellitus. DM etiology, role of immune system. Genetic factors of DM I and DM II. Loci IDDM 1 - IDDM 18, NIDDM 1 - NIDDM 12 and their significance.(7) Lipid metabolism and its regulation. Blood plasma lipoproteins, their characterization. Details in lipoprotein formation and metabolism. Risk factors for atherosclerosis.(8) Cancerogenesis. Physical, chemical and biological background of cancerogenesis. Oncogenes and antioncogenes. Viruses in oncogenesis. Tumor markers and their significance. (9) Metabolism of tumors. Glycolysis in tumors, amino acid metabolism abnormalities (asparagine), nucleotide metabolism abnormalities, membrane abnormalities, glycoproteins as tumor markers, chemotherapy based on metabolic abnormalities. (10) DNA and RNA analysis for diagnostic purposes and for the monitoring of treatment. Detection of mutations. Detection of gene expression, quantification of mRNA production, use of RT PCR, use of micro-arrays. (11) Gene therapy and cell therapy. Possibilities and examples in gene therapy (adenosine deaminase deficiency - SCID). Stem cells - embryonic and tissue stem cells. Ethical problems in gene and stem cells therapy. Examples of applied therapies. (12) Water and mineral metabolism. Distribution of water in the organism. Metabolism of sodium and its regulation. Metabolism of potassium and its regulation. Metabolism of calcium and phosphorus and their regulation. Metabolism of magnesium.(13) Acid-base balance. Conception of acid-base balance. Buffers, function of lungs and kidneys in regulation of acid-base metabolism. Basic terms (acidosis, alkalosis, metabolic and respiratory disorders, compensation). Metabolic acidosis – causes, laboratory changes, ways of compensation. Metabolic alkalosis – causes, laboratory changes, ways of compensation. Respiratory acidosis – causes, laboratory changes, ways of compensation. Respiratory alkalosis – causes, laboratory changes, ways of compensation. Combined disorders of acid-base balance.(14) Oxidative injury of an organism in pathogenesis of common diseases. Free radicals and reactive species of oxygen (nitrogen, chlorine), their creation in vivo. Substantial and enzymatic antioxidants, their role in oxidative damage and in signal transduction.
Annotation
Biochemical background of pathological processes. Pathobiochemistry of carbohydrates, lipids, amino acids, nucleotides and porphyrins. Oncogenesis and metabolism of tumours. Genetic determination of diseases, DNA and
RNA diagnostic examination, gene therapy. Disorders of ions and pH in the internal environment. Disorders of extracellular matrix constituents, the role of proteolytic enzymes and their inhibitors, prion diseases. Reactive oxygen and nitrogen species, free radicals.