Bioenergetics and Carbohydrate Metabolism PDF

Bioenergetics and Carbohydrate Metabolism Caner Geyik, PhD [email protected] Learning Objectives  Describe bioenergetics  Discuss energetics in metabolic reactions  List the ATP production ways  List the pathways of glucose inside the cell  Describe glyc...

Bioenergetics and Carbohydrate Metabolism Caner Geyik, PhD [email protected] Learning Objectives  Describe bioenergetics  Discuss energetics in metabolic reactions  List the ATP production ways  List the pathways of glucose inside the cell  Describe glycolysis and gluconeogenesis  Explain the pentose phosphate pathway  Describe glycogenolysis and glycogenesis  Explain citrate cycle and electron transport chain Bioenergetics  Bioenergetics : Transfer and utilization of energy in biologic systems  Bioenergetics predicts if a process is possible, whereas kinetics measures the reaction rate Molecule 1 Molecule 2 Bioenergetics ΔG = - 20 kcal/mol Energy difference (ΔG): (Final E) – (Initial E) ΔG negative  Spontaneous  Exergonic Bioenergetics ΔG = 20 kcal/mol Energy difference (ΔG): (Final E) – (Initial E) ΔG positive  Nonspontaneous  Endergonic Bioenergetics Bioenergetics ΔG01 ΔG02 Net ΔG0 = ΔG01 + ΔG02 + ΔG03 Glucose + ATP → Glucose 6-phosphate + ADP ΔG01 = -4000 cal/mol Glucose 6-phosphate → Fructose 6-phosphate ΔG02 = +400 cal/mol --------------------------------------------------------------------------------------------- Glucose + ATP → Fructose 6-phosphate + ADP ΔG0 = -3600 cal/mol Bioenergetics ATP: Adenosine triphosphate ATP + H2O → ADP + Pİ ΔG0 = -7,3 kcal/mol ATP + H2O → AMP + PPİ ΔG0 = -10,9 kcal/mol ATP production 1) Substrate-level phosphorylation ATP production 2) Oxidative phosphorylation NADH, FADH2: Electron carriers in ATP synthesis Carbohydrate Metabolism Glycogen Glucose 6- Glycolysis Glucose Pyruvate Phosphate Gluconeogenesis Pentose Phosphate Pathway Ribose 5- Phosphate Glycolysis  Energy production  ATP (substrate level)  NADH (Electron carrier for oxidative ATP production)  Provides intermediates for other metabolic pathways  Amino acids, lipids, and other carbohydrates can be synthesized from intermediate molecules There are three rate-limiting, regulation steps Single arrows: Regulations  Glycolysis Two Stages Investment: Consumes energy, molecules are prepared Harvest: Yields energy by substrate level phosphorylation (ATP), and electron carrier molecules (NADH) - 2 ATP + 4 ATP = 2ATP Hormonal Regulation of Glycolysis Glycolysis – NAD+ Regeneration Fermentation (Lactate or Ethanol) 2 NAD+ 2 NADH O2 absent NADH NAD+ Glucose Pyruvate TCA and ETC O2 present TCA Cycle and Oxidative Phosphorylation TCA Cycle  Citrate Cycle  Citric Acid Cycle (CAC)  Tricarboxylic acid (TCA) Cycle  Krebs Cycle Common Name: Citric acid IUPAC Name: 2-Hydroxypropane-1,2,3-tricarboxylic acid TCA Cycle Glycolysis in cytoplasm TCA in mitochondria  Pyruvate should be transported to mitochondria (regulation by compartmentalization)  Irreversible synthesis of Acetyl-CoA from pyruvate is a link between glycolysis and TCA cycle TCA Cycle (Acetyl-CoA)  Main function of TCA cycle is to harvest the high energy electrons from carbon (Citrate) fuels  Electrons are captured as NADH and FADH2 for production of ATP  Moreover, precursors needed to synthesize various biomolecules can be obtained from TCA cycle (Biosynthetic role) Oxidative Phosphorylation and ETC  Electron Transport Chain Yellow Part  Electrons carried by NADH and FADH2 are captured by the system  With these electrons, oxygen is reduced to water  During this process, ETC- complexes pump H+ to outer membrane Pink Part  Positive charge out of the membrane starts a flow into the matrix.  ATP is synthetized by the energy of this flow. Youtube ETC https://www.youtube.com/watch?v=LQmTKxI4Wn4&t=62s ATP Synthesis (Oxidative) https://www.youtube.com/watch?v=kXpzp4RDGJI  ETC – Overall Picture NADH enters from Complex I , FADH2 enters from Complex II  1 NADH pumps 3 protons ~2,5 ATP  1 FADH2 pumps 2 protons ~1,5 ATP Energy Gained from 1 mol Glucose (Oxidative State) 1 mol 2 mol +2 NADH 2 mol Glucose Glycolysis Pyruvate PDH Acetyl-CoA +2 ATP +2 NADH Cytoplasm +2 ATP +6 NADH +2 FADH2 Mitochondria  Transfer of Cytoplasmic NADH to Mitochondria Malate Aspartate Shuttle  NADH can’t enter  After a series of reactions NADH is formed inside the mitochondria 1 NADH → 1 NADH  Transfer of Cytoplasmic NADH to Mitochondria Glycerol 3-phosphate Shuttle  NADH can’t enter  After a series of reactions FADH2 is formed inside the mitochondria 1 NADH → 1 FADH2  Energy Gained from 1 mol Glucose (Oxidative State) 1 mol 2 mol +2 NADH 2 mol Glucose Glycolysis Pyruvate PDH Acetyl-CoA +2 ATP +2 NADH Cytoplasm +2 ATP +6 NADH +2 FADH2 TOTAL : 36 or 38 ATP 4 ATP (2 from glycolysis, 2 from TCA) 2 FADH2 (from TCA) = 4 ATP 8 NADH (2 from PDH, 6 from TCA) = 24 ATP Mitochondria 2NADH (glycolysis) = 4 or 6 ATP (depending on shuttle) Carbohydrate Metabolism Glycogen Glucose 6- Glycolysis Glucose Pyruvate Phosphate Gluconeogenesis Pentose Phosphate Pathway Ribose 5- Phosphate  Gluconeogenesis Hexokinase Glucose 6-phosphate Phosphofructokinase- Fructose 1,6- 1 (PFK-1) bisphosphatase PEP carboxykinase Pyruvate kinase Pyruvate carboxylase Carbohydrate Metabolism Glycogen Glucose 6- Glycolysis Glucose Pyruvate Phosphate Gluconeogenesis Pentose Phosphate Pathway Ribose 5- Phosphate Glycogen  Blood glucose can be obtained from three primary sources:  Diet  Gluconeogenesis  Glycogen degradation  Dietary intake of glucose is sporadic, not always a reliable source of blood glucose  Gluconeogenesis, can provide sustained synthesis of glucose, but it is slow in responding to a falling blood glucose level  Therefore, the body has developed mechanisms for storing a supply of glucose in a rapidly mobilized form, namely, glycogen. Glycogen  Homopolysaccharide (-D-glucose)  Branched-chain  Chain (Linear) part -(1,4)  Branch part -(1,6)  A protein at the center (glycogenin) Glycogen  Skeletal Muscle  For itself  Rapid demand for ATP  2% of total weight  Local and fast resource  Liver  For itself and all body  Regulates blood glucose levels  10% of total weight Glycogen Metabolism Glycogen  Synthesis  Glucose 1-P, needs to be activated by UDP before integration to glycogen UDP- Glucose  Degradation  Glucose 1-P molecules are cleaved Glucose from the end of the chains 1-Phosphate  1 mol free glucose is obtained from the branching site Glucose Glucose 6-Phosphate Carbohydrate Metabolism Glycogen Glucose 6- Glycolysis Glucose Pyruvate Phosphate Gluconeogenesis Pentose Phosphate Pathway Ribose 5- Phosphate Pentose Phosphate Pathway Main Products Oxidative  Ribose 5-phosphate Reactions (Irreversible)  NADPH Non-oxidative Reactions (Reversible) Pentose Phosphate Pathway Oxidative Reactions  Glucose 6-P →Ribulose 5-P + CO2 + 2 NADPH Pentose Phosphate Pathway Non-oxidative Reactions  Ribose 5-P: Nucleotide and Nucleic acid synthesis  Glycolysis intermediates Pentose Phosphate Pathway Nucleic acid synthesis Ribulose 5-P