The course of Biochemistry aims to provide to the students the basis to understanding the physical, chemical and biological contexts in which molecules, reactions and metabolic pathways play their role. Particular attention will be given to the structure and function relationship of the major classes of macromolecules as also to the metabolic regulation at the molecular and cellular level.
In order to stimulate student interest the topics will be explained emphasizing the logical and consequential interconnections enphasizing the clinical aspects and introducing experimental methods.
At the end of the present course the student will understand the structure-function relationships of the main biological molecules, essential biochemical mechanisms that underlie a proper metabolic function and the consequences of their alterations.
Beta-oxidation of fatty acids (role of carnitine, chemical reactions, energy yield, oxidation of fatty acids with odd number of carbon atoms and vitamin B12, oxidation of unsaturated fatty acids, peroxisomal beta-oxidation, alpha-oxidation). Lipolysis, hormone-sensitive lipase and its regulation.
Biosynthesis of ketone bodies; utilization of ketone bodies; diabetic ketoacidosis.
Fatty acid biosynthesis: transport of acetyl-CoA from the mitochondria to the cytoplasm (the role of citrate and carnitine), acetyl- carboxylase and biotin, fatty acid synthase, and acyl carrier protein, regulation of the synthesis of fatty acids, chain elongation reactions (microsomal and mitochondrial); mechanism of the desaturation; essential fatty acids; arachidonic acid derivatives (eicosanoids): prostaglandins, prostacyclin, thromboxanes, leukotrienes.
Biosynthesis of triglycerides. Metabolic pathways of conversion of sugar into fat.
Biosynthesis and degradation of phospholipids, sphingolipids, and glycolipids.
Digestion of lipids; pancreatic lipase, biliary salts; micelles and intestinal absorption of lipid; pancreatic juice, bile composition, cholecystokinin-pancreozymin, secretin, steatorrhea (pancreatic insufficiency and biliary insufficiency), biosynthesis of triglycerides in the intestine (monoglycerides pathway); chylomicrons; biosynthesis of triglycerides (liver and adipose tissue); methods of separation of lipoproteins (electrophoretic separation on agarose gel; separation by ultracentrifugation at increasing density); classification and chemical composition of lipoproteins (chylomicron, VLDL, LDL, HDL ); role of lipoproteins in the transport of exogenous and endogenous fat; lipoprotein lipase; blood transport of non-esterified fatty acids (NEFA) in the form of complexes with albumin; receptor-mediated endocytosis of LDL; regulation of the synthesis of cholesterol and LDL receptors by intracellular cholesterol. Cholesterol biosynthesis and its regulation; bile acid biosynthesis; enterohepatic circulation; biosynthesis of biliary acids; biosynthesis of vit. D; biosynthesis of steroid hormones.
Classification and molecular pathogenesis of hyperlipidemia.
Amino acid metabolism.
Digestion of proteins: mechanism of HCl secretion in the stomach; gastric protease (pepsin); pancreatic proteases (trypsin, chymotrypsin, elastase, carboxypeptidase); intestinal peptidases (aminopeptidase, tripeptidase, dipeptidase); intestinal absorption of amino acids
Essential and non-essential amino acids. Nitrogen balance, daily protein requirement, biological value of protein.
Catabolism of amino acids: oxidative deamination and transamination of amino acids, glutamine synthetase, glutaminase and functions of glutamine, "muscle-liver"alanine cycle; urea cycle; correlation between the urea cycle and tricarboxylic acid cycle, glucogenic and ketogenic amino acids.
Biosynthesis of nonessential amino acids.
Synthesis of serine from 3-phosphoglycerate; serine transhydroxymethylase and tetrahydrofolate; non-oxidative deamination of serine and threonine (serine threonine dehydratase)
Glycine: serine-glycine conversion, glycine synthase. Heme biosynthesis (see hemoglobin metabolism); role in the biosynthesis of creatine, glutathione and purine nucleotides.
Metabolism of phenylalanine and tyrosine: catabolism to fumarate and acetoacetate, biosynthesis of melanin, biosynthesis catecholamines (dopamine, noradrenaline and adrenaline). Degradation of catecholamines. Phenylketonuria, alkaptonuria, albinism.
Tryptophan metabolism; biogenesis of nicotinic acid. Biosynthesis and degradation of serotonin
Metabolism of methionine and S-adenosyl-methionine. Methyl cycle and role of folic acid and vitamin B12.
Decarboxylation of amino acids: biosynthesis of polyamines, catecholamines, serotonin, histamine and GABA.
Metabolism of cysteine (with taurine and glutathione synthesis)
Arginine metabolism and synthesis of NO.
Metabolism of branched chain amino acids (valine, isoleucine, leucine).
Biosynthesis, transport and degradation of proteins.
Integration and hormonal control of glucidic, lipid and protein metabolism during the fasting-feeding cycle.
Metabolism of hemoglobin.
Iron metabolism. Biosynthesis and catabolism of heme. Hyperbilirubinemia.
Biosynthesis "de novo" of pyrimidine nucleotides and its regulation. De novo biosynthesis of purine nucleotides and interconversion. Conversion of ribonucleotides into deoxyribonucleotides. Salvage pathways. Purine catabolism and uric acid; hyperuricemia (primary and secondary gout).
Cell and tissue biochemistry.
Mechanisms of DNA repair and correlations with the phenomena of cellular aging and with human diseases (in particular with cancer).
Pathways of signal transduction.
Receptors with seven transmembrane domains, G proteins, enzyme effectors (adenylyl cyclase, phospholipase C), second messengers (cAMP, IP3, DAG, Ca+ +). Phosphoinositide cycle. PKA and PKC. Cyclic GMP and NO. Receptors with tyrosin kinase activity. Kinase cascades. Transduction pathways through PI3K/PKB. The MAP kinase pathway. JAK-STAT pathway.
Biochemical aspects of the cell cycle and apoptosis.
Biochemistry of metals
Iron and copper: cellular homeostasis and human diseases.
Biosynthesis and degradation, release, metabolic and other physiological effects, receptors, signal transduction pathways of the following hormones: glucagon, insulin, adrenaline and noradrenaline, hypothalamic and pituitary hormones, thyroid hormones, steroid hormones (glucocorticoids, mineralocorticoids, sex hormones), parathyroid hormone, calcitonin and vit D. Hormonal regulation of salt and water balance.
Plasma and serum. Plasma proteins. Blood clotting.
Biochemistry of the liver.
Metabolic roles. Detoxification processes. Reactions of phase 1: the cytochrome P450 CYP enzymes. Reactions of stage 2. Hepatic metabolism of ethanol.
Muscle tissue and biochemistry of physical exercise.
Classification of muscle fibers. Muscle bioenergetics: exoergonic mechanisms in muscle contraction: anaerobic (alactacid and lactacid) and aerobic metabolism. ATP, phosphocreatine and creatine kinase, adenylate kinase or miokinase, anaerobic threshold, anaerobic glycolysis and glycogen, beta-oxidation and carnitine; anaerobic and aerobic exercise, oxygen debt.
Principles of Neurochemistry
Neurotransmission: neurotransmitter, the synapse (presynaptic terminal, synaptic vesicles, mitochondria, pre-and post-synaptic membrane, synaptic cleft). Postsynaptic receptors: ionotropic receptors and receptors coupled to second messengers (metabotropic receptors).
Biosynthesis and functional aspects of noradrenaline, dopamine, serotonin, acetylcholine, glutamate, GABA.