84286 - Metabolic Biochemistry

Course Unit Page

  • Teacher Giorgio Lenaz

  • Credits 6

  • SSD BIO/10

  • Teaching Mode Traditional lectures

  • Language English

Academic Year 2017/2018

Learning outcomes

Define the major pathways of intermediary metabolism of biomolecules, and discuss their bioenergetics, physiological adaptation, metabolic and main hormonal regulation, localization and cellular compartmentalization. Correlate the metabolic activity of tissues and organs with their function. Discuss how disruptions in intermediary metabolism may lead to disease, and illustrate with selected examples.

Course contents

Lecture 1. INTRODUCTION TO METABOLISM.

Metabolic pathways. Steady state. Catabolism and anabolism. Coupling catabolic and anabolic pathways through adenyl nucleotides (ATP/ADP/AMP) and pyridine nucleotides (NAD(P)+ / NAD(P)H). Metabolism and cellular structure. Principles of metabolic regulation. ATP synthesis: substrate-level phosphorylation and oxidative phosphorylation. Utilization of ATP: orthophosphoric and pyrophosphoric cleavage.

Lecture 2. OXIDATIVE PHOSPHORYLATION (1).

General principles: converging reducing equivalents from metabolism to oxygen. Structure of the mitochondria. The mitochondrial respiratory chain: respiratory complexes and their cofactors (pyridine nucleotides, flavins, iron-sulfur clusters, Coenzyme Q, cytochromes, copper); respiratory supercomplexes; mechanism of electron transfer and proton translocation.

Lecture 3. OXIDATIVE PHOSPHORYLATION (2)

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 (hints).

Lecture 4. OVERVIEW OF CARBOHYDRATE METABOLISM.

Structure of the main carbohydrates. Digestion and absorption. General scheme of carbohydrate metabolism in liver and extra-hepatic tissues. Blood glucose and its regulation.

Lecture 5. GLYCOGEN METABOLISM

Phosphorylation of glucose. Glycogen synthesis and glycogenolysis and their regulation in liver and muscle

Lecture 6 GLYCOLYSIS (1)

Reactions of glycolysis, substrate-level phosphorylation, regulation.

Lecture 7. GLYCOLYSIS (2)

Re-oxidation of glycolytic NADH: lactate fermentation, aerobic oxidation (malate/aspartate shuttle and glycerol-phosphate shuttle). Energetic balance.

Lecture 8. PYRUVATE OXIDATION AND TCA CYCLE

Pyruvate oxidation: pyruvate dehydrogenase complex and its mechanism.

The tricarboxylic acid (TCA) cycle: reactions, substrate-level phosphorylation, regulation. The TCA cycle as a terminal metabolic pathway. Anaplerotic reactions: pyruvate carboxylase, mechanism and regulation. Biosynthetic role of the TCA cycle.

Lecture 9. GLUCONEOGENESIS

Gluconeogenesis: carbon and hydrogen sources; the reactions of gluconeogenesis. Regulation: hormonal control of glycolysis and gluconeogenesis in liver.

Lecture 10. PENTOSE PHOSPHATE PATHWAY (PPP)

The pentose phosphate pathway or pentose phosphate shunt: reactions and metabolic role: source or disposal of pentoses, reducing power for biosynthesis.

Lecture 11. HORMONAL REGULATION OF BLOOD GLUCOSE.

Hormonal regulation of blood glucose: insulin, glucagon, cortisol. Defects in glycaemia control: diabetes.

Lecture 12. OVERVIEW OF LIPID METABOLISM

Structure of the main lipids. Digestion, absorption and transport of dietary lipids. Role of bile salts. Lipolysis. Hormone-dependent triglyceride lipase. Non-esterified fatty acids (NEFA) in the blood.

Lecture 13. 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. Ketone bodies Fasting and ketogenesis: relation with gluconeogenesis. Steps of ketogenesis. Ketone bodies utilization.

Lecture 14. BIOSYNTHESIS OF FATTY ACIDS

Biosynthesis of fatty acids. De novo synthesis of palmitate, steps, energetics and reducing power. Regulation. Compartmentalization: role of citrate. Elongation and desaturation. Essential fatty acids and derivatives (ω3 and ω6 families).

Lecture 15. BIOSYNTHESIS OF LIPIDS

Biosynthesis of glycerol lipids: synthesis of phosphatidic acid. Synthesis of triacylglycerols and the major glycerophospholipids. Role of cytidine nucleotides. Hints on the synthesis of plasmalogens, sphingomyelin and glycolipids.

Lecture 16. BIOSYNTHESIS OF CHOLESTEROL

Steps of cholesterol biosynthesis: cytosolic acetylCoA, synthesis of mevalonate, formation of active isoprene (isopentenyl pyrophosphate), polymerization to squalene, and cyclization. Synthesis of cholesteryl esters and transport in lipoproteins. Derivatives of cholesterol: bile acids, Vitamin D3, steroid hormones. Other isoprenoid compounds. Regulation of cholesterol synthesis.

Lecture 17. METABOLISM OF PLASMA LIPOPROTEINS

Structure and classification of lipoproteins. Origin, composition and transport of the different lipoprotein classes.

Lecture 18. METABOLISM OF NITROGEN COMPOUNDS.

General scheme of nitrogen metabolism. Digestion of proteins and absorption of aminoacids . Essential aminoacids. Intracellular protein degradation. Deamination of aminoacids: Nonoxidative and oxidative deamination. D-aminoacid oxidase. Glutamate dehydrogenase. Trans-deamination. Mechanism of transaminase reactions. Pyridoxal phosphate.

Lecture 19. FATE OF AMMONIA

Ureotelic animals. Urea cycle: reactions and regulation. Fate of NH3 in extrahepatic tissues: glutamine synthesis and transport. Alanine cycle.

Lecture 20. FATE OF THE CARBON SKELETON OF AMINOACIDS

Gluconeogenesis. Glucogenic and ketogenic aminoacids. Relation with TCA cycle. Formation of acetylCoA: complete oxidation or lipogenesis. Aminoacid decarboxylation: biogenic amines. Polyamines.

Synthesis of non-essential aminoacids. Hints of reactions involved

Lecture 21. METABOLISM OF 1-CARBON UNITS

Metabolism of 1C units: role of FH4. Synthesis and catabolism of purine nucleotides and salvage patrhways. Synthesis of pyrimidine nucleotides. Synthesis of deoxyribonucleotides. Synthesis of thymidylate. Methionine and methyl group transfer. Role of vitamin B12.

Lecture 22. BIOSYNTHESIS AND CATABOLISM OF PORPHYRINS

Biosynthesis of heme. Heme catabolism and bilirubin transport. Jaundice. Concluding remarks on nitrogen metabolism.

Lecture 23. METABOLIC INTEGRATION

Interrelations between metabolic pathways. Interrelations between liver and peripheral tissues. Biochemistry of fasting and feeding conditions.

Lecture 24 . SPECIFIC METABOLISM OF SOME ORGANS AND TISSUES (HINTS)

An overview of specific aspects of metabolism in different organs an d tissues (brain, kidney, liver, skeletal muscle, heart, adipose tissue, blood).

Office hours

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