|
Lecturer(s)
|
-
De Clercq Erik, prof. Dr. Ph.D.
-
Grubhoffer Libor, prof. RNDr. CSc.
|
|
Course content
|
Content of lectures: 1. Capping of viral mRNA - Methyltransferase - S-adenosylmethioine (SAM)/ S-adenosylhomocysteine (SAH) - SAH hydrolase (inhibitors) - Antiviral activity. Restriction endonucleases - sickle cell anemia - prenatal diagnostics of sickle cell anemia. 2. De novo biosynthesis of purine mononucleotides - IMP dehydrogenase - Inhibitors of IMP dehydrogenase (i.e. ribavirin). De novo biosynthesis of pyrimidine mononucleotides - orotic acid aciduria. Thymidylate synthase - Folic acid (Folate) - Folate metabolites (N5,N10-methylene-FH4 , N5,N10-methenyl-FH4, N10-formyl-FH4) - Folate (folid acid) antagonists [Aminopterine, Amethopterine (Methotrexate)] - Creation of a carbon-carbon bond. 3. Catabolism of purine monucleotides - Uric acid - Gout - Alcohol metabolism - Lesch-Nyhan syndrome - Allopurinol (treatment of gout). Catabolism of pyrimidine monucleotides - Dihydropyrimidine dehydrogenase (DPD) - 5-Fluorouracil - Antitumor activity. 4. Biosynthesis of heme - Porphyrias (hepatic, erythropoietic and hepato-erythropoietic porphyrias) - Lead poisoning. Degradation of heme - Indirect and direct bilirubin - Bilirubin and bilirubin diglucuronate - Jaundice (prehepatic, hepatic, posthepatic). 5. Glycolysis - Pyruvate kinase - Pentose phosphate shunt pathway - Inherited hemolytic anemias - Role of NADPH-glucose-6-phosphate dehydrogenase. 6. Biosynthesis of cholesterol - HMGA reductase - Hypocholesterolemic agents. Biosynthesis of bile acids from cholesterol - ?-oxidation - peroxisomes - cholestanic acid aciduria - Role of bile acids in the digestion of nutritional lipids. Biosynthesis of steroid hormones from cholesterol (congenital adrenal hyperplasia) - Desmolase, 3-?-ol dehydrogenase, 21-hydroxylase, ?aromatase. 7. Aminotransferases [alanyltransaminase (ALT), aspartyltransaminase (AST)] - Role in intermediary metabolism (citric acid cycle) - Role in diagnostics of hepatitis A, B, C and myocard infarct. Urea cycle - ?-Glutamyl cycle - ?-aminobutyric acid cycle - Hyperammonemia - Chinese restaurant syndrome - Liver coma. 8. CO and NO - Biosynthesis - Mechanism of action - cGMP - Phosphodiesterase - Penile erection function - Sildenafil (ViagraTM). Creatine and creatinine - Biosynthesis - Biological role - Creatine phosphokinase (CPK) - Muscle activity - Myocard infarct - Creatinine clearance. 9. Acetylcholine esterase - Acetylcholinesterase inhibitors - Acetylcholine as neurotransmittor - Therapeutic applications of acetylcholinesterase inhibitors. Dopamine, Noradrenaline, Serotonine, Melatonine - Parkinson's disease (dopamine) - Carcinoid tumor [5-hydroxy-indole acetic acid (HIAA)]. Catecholamine (dopamine, noradrenaline, adrenaline) catabolism Pheochromocytoma [VMA (vanilmandelic acid)] - Neuroblastoma (Homovanillinic acid). 10. Biosynthesis of polypeptide hormones (i.e. parathyroid hormone) - Hypo- and hyperparathyroidea - Biosynthesis of thyroid hormones (T3, T4) - Thyrotoxicosis. Biochemical background of diabetes mellitus - Hyperglycemia - Neoglucogenesis - Ketoacidosis. 11. Vit. A: provitamin A, vitamin A, active metabolite of vitamin A - Mode of action - Pathology. Vit. D: provitamin D, vitamin D, active metabolite of vitamin D - Mode of action - Pathology. Vit. B12 : structure : Formation of N5-methyl FH4 - Conversion of methylmalonyl-CoA to succinyl CoA - Citric acid cycle - Pernicious anemia - Megaloblastic anemia. 12. Antibiotics: mechamismss of action, development and transmission of resistance. 13. Antivirals active against DNA viruses/retroviruses (overview). 14. Antivirals active against RNA viruses (overview).
|
|
Learning activities and teaching methods
|
Monologic (reading, lecture, briefing), Work with text (with textbook, with book), Work with multi-media resources (texts, internet, IT technologies)
- Class attendance
- 26 hours per semester
- Preparation for exam
- 25 hours per semester
- Semestral paper
- 25 hours per semester
|
|
Learning outcomes
|
The course that is composed of individual lessens has covered currently topic subjects of modern medicinal biochemistry including development of antibiotics and antivirals as powerfull (tools against infectious agents, and mechanisms of acquired and inherited human illnesses at the molecular and biochemical level). The course provides a broad array of advanced knowledge of medicinal chemistry and biochemistry.
Students will understand the possibilities of biochemistry in the development of novel drugs.
|
|
Prerequisites
|
Knowledge of biochemistry, molecular and cellular biology.
|
|
Assessment methods and criteria
|
Seminar work, Interim evaluation
Students must correctly answer at least 50 % of test questions, presentation of a selected topic.
|
|
Recommended literature
|
-
Doporučená učebnice Biochemie: L. Stryer, J.M. Berg & J.L. Tymoczko (Eds.) Biochemistry. Freeman & Co., 5th ed., 1100 pp., 2002..
-
E. De Clercq & A. Holý: Acyclic nucleoside phosphonates: a key class of antiviral drugs. Nature Rev. Drug Discovery 4: 928-940, 2005..
-
E. De Clercq: Antiviral agents active against influenza A viruses. Nature Rev. Drug Discovery 5: 1015-1025, 2006..
-
E. De Clercq: Antiviral drugs in current clinical use. J. Clin. Virol. 30: 115-133, 2004..
-
E. De Clercq: Antivirals and antiviral strategies. Nature Rev. Microbiol. 2: 704-720, 2004..
-
E. De Clercq: Status presens of antiviral drugs and strategies: part I, DNA viruses and retroviruses; part II, RNA viruses (except retroviruses). Adv. Antiviral Drug Design, vol. 5, in press (2007)..
-
E. De Clercq: Strategies in the design of antiviral drugs. Nature Reviews Drug Discovery 1: 13-25, 2002..
-
E. De Clercq: The bicyclam AMD3100 story. Nature Rev. Drug Discovery 2: 581-587, 2003..
|