Energy metabolism - the overview

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1 Energy metabolism - the overview Josef Fontana EC - 40

2 Overview of the lecture Important terms of the energy metabolism The overview of the energy metabolism The main pathways of the energy metabolism Specialization of organs in the energy metabolism (liver, kidney, muscle, adipose tissue and brain) Interorgan metabolic pathways Overview of hormonal regulation of the energy metabolism Effect of insulin and counter-regulatory hormones on the energy metabolism

3 Important terms of the energy metabolism

4 Important terms of the EM Metabolism is the set of catabolic and anabolic reactions Components of metabolic pathways are intermediates - metabolites Catabolic reactions: fission reactions (reactions of degradation) Anabolic reactions: synthetic reactions Some pathways have catabolic as well as anabolic character - amphibolic

5 The overview of the energy metabolism The main pathways of the energy metabolism

6 Picture adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley- Liss, Inc., New York, ISBN

7 Picture adopted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley- Liss, Inc., New York, ISBN

8 The main pathways of the EM Catabolic reactions glycolysis glycogenolysis (degradation of glycogen) lipolysis beta-oxidation ketone bodies degradation degradation of AA, proteolysis

9 The main pathways of the EM Anabolic reactions: glycogenesis gluconeogenesis lipogenesis (synthesis of TAG), synthesis of FA ketogenesis proteosynthesis synthesis of AA urea synthesis

10 The main pathways of the EM Main reactions: pyruvate dehydrogenase reaction Krebs cycle respiratory chain

11 Major intermediates are acetyl-coa pyruvate NADH

The figure is found at http://www.elmhurst.

12 The figure is found at (December 2006)

14 pyruvate (PDH) i.e. from glucose amino acids (degrad.) from proteins fatty acids (β-oxidation) from TAG ketone bodies (degrad.) from FA acetyl-coa citrate cycle, RCH CO 2, H 2 O, ATP synthesis of FA synthesis of ketone bodies synthesis of cholesterol synthesis of glucose!!!

15 aerobic glycolysis oxidation of lactate (LD) degradation of some amino acids pyruvate acetyl-coa (PDH) lactate (lactate dehydrogenase) alanine (alanine aminotransferase) oxaloacetate (pyruvate carboxylase) glucose (gluconeogenesis)

16 aerobic glycolysis PDH reaction β-oxidation citrate cycle oxidation of ethanol NADH pyruvate lactate respiratory chain reoxidation to NAD + energy storage in ATP! OXYGEN SUPPLY IS NECESSARY!

17 The most important is to answer these questions What? Where? When? How? Why?

18 The overview of the energy metabolism Specialization of organs in the energy metabolism (liver, kidney, muscle, adipose tissue and brain)

19 Liver Unique position in the intermediary metabolism Role in the maintenance of homeostasis, synthesis of molecules, mutual transformation of nutrients and in the regulation of storage and release of energy Affect metabolism of saccharides, lipids, proteins and amino acids

20 Liver Short-term and long glycemic control High glucose levels in portal blood (after a meal) - glycogen synthesis in liver Decrease of blood glucose (during fasting) glycogen is degraded (glycogenolysis) glucose release into the blood Depletion of glycogen stores production of glucose from non-saccharide substrates (gluconeogenesis)

21 Liver Deamination or transamination of AAs subsequent conversion of the carbon skeleton to glucose or lipids Removal of ammonia from the body - synthesis of urea (ammonia is toxic) Synthesis of nonessential amino acids Production of almost all plasma proteins

22 Kidney Transport of various substances requires large amounts of energy ATP is obtained from the oxidative metabolism of Glc, lactate, fatty acids and amino acids Gluconeogenesis Enzymes involved in amino acid metabolism

23 Muscle Muscle contraction requires lot of ATP Sources of ATP: phosphocreatine anaerobic glycolysis aerobic glycolysis + oxidative phosphorylation muscle glycogen nutrients from the circulation: glucose and fatty acids

24 Muscle Degradation of branched amino acids (Val, Leu, Ile) Carbon skeletons of AAs are used in energy metabolism (Krebs cycle) -NH2 groups are used for synthesis of Ala, Glu and Gln Glucose alanine cycle

25 Adipose tissue TAG storage (postprandial) Lipoprotein lipase LPL (endothelial) De novo lipogenesis: from glucose Lipolysis = FA + glycerol release (fasting) Hormone-sensitive lipase (IC)

26 Brain 2% of body weight, 20% of energy expenditure Glucose is the main fuel: daily consumption 120g Adopted starvation (3 weeks): oxidation of ketone bodies in the brain covers up to 50% of energy

27 The overview of the energy metabolism Interorgan metabolic pathways

28 Interorgan metabolic pathways There are many interorgan metabolic pathways in the energy metabolism Two of them: 1) Cori cycle 2) Glucose alanine cycle

29 Cori cycle and muscle The figure was accepted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley Liss, Inc., New York, ISBN

30 Figure is found on

31 Glucose-alanine cycle The figure was accepted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley Liss, Inc.,

32 Figure is found on

33 Overview of hormonal regulation of the energy metabolism Effect of insulin and counterregulatory hormones on the energy metabolism

34 Remebrer forever!

35 The actions of insulin Anabolic effects Storage of glucose (mainly in liver) Activates glycolysis and glycogen formation, and conversely blocks gluconeogenesis Increases the number of GLUT-4 channels All these steps reduce blood glucose

36 The actions of insulin Excessive carbohydrate intake conversion of glucose to fatty acids Transport of TAG to the adipose tissue Inhibits lipolysis and ketogenesis Formation of proteins - proteoanabolic hormone Tissue growth

37 The actions of glucagon Antagonize the effects of insulin (via camp) Maintains glycemia between meals and during increased glucose consumption: 1) stimulates glycogenolysis (liver) 2) stimulates gluconeogenesis from lactate, AAs (protein catabolism) and glycerol (lipolysis)

Integrative Metabolism: Significance

Integrative Metabolism: Significance Energy Containing Nutrients Carbohydrates Fats Proteins Catabolism Energy Depleted End Products H 2 O NH 3 ADP + Pi NAD + NADP + FAD + Pi NADH+H + NADPH+H + FADH2 Cell