00061 - Biochemistry (C)

Learning outcomes

At the end of the course, the student will know: the essential elements of the intermediary metabolism of major biological molecules (carbohydrates, lipids, and nitrogenous compounds), the associated energy modifications, their interrelationships and metabolic and hormonal regulations, as well as the cellular localization and compartmentalization of the main metabolic pathways; the specialization of various human organs and tissues in metabolic activities as a prerequisite for understanding their specific functions; the molecular mechanisms of cellular activity regulation with particular regard to intracellular signal transduction and the function of hormones, other extracellular messengers, and vitamins at the metabolic and genetic levels; the biochemical principles underlying human nutrition with particular emphasis on the molecular mechanisms of nutrient digestion and absorption and essential nutritive principles with references to nutrigenomics.

Course contents

INTRODUCTION TO METABOLISM

Utilization of ATP: orthophosphoric and pyrophosphoric cleavage. Catabolism and anabolism. Metabolic pathways and their regulation. Modulation of activity and synthesis of enzymes. Protein kinases and phosphatases. Oxido-reductases.

 

CARBOHYDRATE METABOLISM

Structure of the main carbohydrates. Digestion and absorption. Glucose transporters. Blood glucose and its regulation. General scheme of carbohydrate metabolism.

GLYCOGEN METABOLISM. Glycogen synthesis, glycogenolysis and their regulation.

GLYCOLYSIS and GLUCONEOGENESIS. Reactions of glycolysis, regulation and energetic balance. Re-oxidation of glycolytic NADH: lactate fermentation, aerobic oxidation (malate/aspartate shuttle and glycerol-phosphate shuttle). The reactions of gluconeogenesis, carbon and hydrogen sources. Regulation: hormonal control of glycolysis and gluconeogenesis.

PENTOSE PHOSPHATE PATHWAY (or SHUNT). Reactions and metabolic role: source or disposal of pentoses, reducing power for biosynthesis.

Metabolic use of fructose and galactose; formation of glucuronic acid

 

PYRUVATE OXIDATION, TCA CYCLE, OXIDATIVE PHOSPHORYLATION

Pyruvate oxidation: pyruvate dehydrogenase complex and its mechanism. The tricarboxylic acid (TCA) cycle: reactions, regulation and energetic balance. The TCA cycle as a terminal metabolic pathway. Biosynthetic role of the TCA cycle. Anaplerotic reactions.

MITOCHONDRIAL RESPIRATORY CHAIN and OXIDATIVE PHOSPHORYLATION.

Structure of mitochondria. The mitochondrial respiratory chain: respiratory complexes and their cofactors; mechanism of electron transfer and proton translocation. Chemio-osmotic coupling. ATP synthase and mechanism of ATP synthesis. Energy-linked reactions. Respiratory control, uncouplers. Uncoupling proteins. Generation of reactive oxygen species. Mitochondrial DNA.

 

LIPID METABOLISM

Structure of the main lipids. Digestion, absorption and transport of dietary lipids. Role of bile salts. Structure and classification of lipoproteins. Origin, composition and transport of different lipoprotein classes.

LIPOLYSIS and FATTY ACID OXIDATION. Beta-oxidation of fatty acids. Fatty acid activation. Transport to the mitochondrial matrix and role of carnitine. Steps of beta-oxidation. Oxidation of odd-chain and of unsaturated fatty acids. Energetics of fatty acids oxidation. Lipolysis and its regulation. Non-esterified fatty acids (NEFA) in the blood. Ketone bodies: ketogenesis and its relation with gluconeogenesis. Ketone bodies utilization.

BIOSYNTHESIS OF FATTY ACIDS, LIPIDS and CHOLESTEROL. De novo synthesis of palmitate: steps, energetics and reducing power. Regulation. Compartmentalization: role of citrate. Elongation and desaturation of fatty acids. Biosynthesis of glycerol lipids: synthesis of phosphatidic acid, triacylglycerols and major glycerophospholipids. Synthesis of sphingolipids. Steps of cholesterol biosynthesis and its regulation. Synthesis of cholesteryl esters and transport in lipoproteins. Derivatives of cholesterol: bile acids, steroid hormones.

 

METABOLISM OF NITROGEN COMPOUNDS

General scheme of nitrogen metabolism. Digestion of proteins and absorption of aminoacids. Intracellular protein degradation.

FATE OF NITROGEN and CARBON SKELETON OF AMINOACIDS. Deamination of aminoacids: non-oxidative and oxidative deamination. Glutamate dehydrogenase. Trans-deamination. Mechanism of transaminase reactions. Urea cycle: reactions and regulation. Fate of ammonia in extrahepatic tissues: glutamine synthesis and transport. Alanine cycle. Glucogenic and ketogenic aminoacids. Relation with TCA cycle and formation of acetylCoA.

Aminoacid decarboxylation: biogenic amines. Polyamines. Essential aminoacids and synthesis of non-essential aminoacids. Metabolism of 1C units: role of FH4. Methionine and methyl group transfer. Role of B12 coenzymes. Synthesis and catabolism of purine nucleotides and salvage pathways. Synthesis of pyrimidine nucleotides. Synthesis of deoxyribonucleotides and thymidylate. Biosynthesis of heme. Heme catabolism and bilirubin transport.

 

METABOLIC INTEGRATION

Interrelations between metabolic pathways. Role of tissues during fasting and feeding conditions. Brain and muscle energy metabolism.

Readings/Bibliography

Slides will be available to the students on the platform "Virtuale".

• D.L. Nelson, M.M. Cox "I principi di Biochimica di Lehninger". Zanichelli editore.

• M. Lieberman, A.D. Marks "Biochimica Medica: un approccio clinico". Casa Editrice Ambrosiana

• T.M. Devlin "Biochimica con aspetti clinici". EdiSES

• D. Voet, J.G. Voet, C.W. Pratt "Fondamenti di Biochimica". Zanichelli

Teaching methods

Lectures

Assessment methods

Oral exam: The Biochemistry exam consists of an interview conducted by the professors of the course (Prof. F. Flamigni, Prof.ssa S. Cetrullo, Prof. Agnetti, e Prof.ssa D'Adamo).

Partial grades obtained contribute to the final grade of the Biochemistry Course, resulting from an overall assessment that takes into account the credits of the various parts.

Teaching tools

Video projector, PC with possible Internet connection, blackboard.

Office hours

See the website of Flavio Flamigni