1. NS 315 Unit 4: Carbohydrate Metabolism Jeanette Andrade MS,RD,LDN,CDE Kaplan University

2. Objectives We want to learn about: Glycolysis and ATP formation Understand Gluconeogenesis, when, where and how Krebs Cycle and Electron Transport Chain

3. Definitions Glycolysis: central pathway for the catabolism of carbohydrates; occurs in most organs Gluconeogenesis: Biosynthesis of new glucose; occurs mainly in liver Krebs cycle- series of enzymatic reactions in aerobic organisms involving oxidative metabolism of acetyl units and producing high- energy phosphate compounds, which serve as the main source of cellular energy Electron Transport Chain (ETC)- Composed of mitochondrial enzymes that transfers electrons from one transport to another, resulting in the driving force for the formation of ATP Oxidative phosphorylation- Process occurring in the cell, which produce energy and synthesizes ATP

4. Definitions Pyruvate: final 3 carbon molecule of glycolysis, involved in the Krebs cycle which facilitates energy production Adenosine diphosphate/Adenosine triphosphate: energy storing molecule used by an organism on a daily basis NAD/NADPH: Reducing agent in several anabolic reactions such as lipid and nucleic acid FAD/FADH: Reducing agent in several anabolic reactions such as lipid Aerobic: in the presence of oxygen Anaerobic: no presence of oxygen

5. Glycolysis Animation http://highered.mcgraw- hill.com/sites/0072507470/student_view0/chapter2 5/animation__how_glycolysis_works.html

6. Fates of Pyruvate Under aerobic conditions Under anaerobic conditions In most aerobic organisms, pyruvate continues in the formation of Acetyl CoA and NADH that follows into the Krebs cycle and Under anaerobic conditions, such as during exercise or in red blood cells (no mitochondria), pyruvate is reduced to lactate by lactate dehydrogenase producing NAD for glycolysis

7. Pathways during Glycolysis Aerobic- with oxygen The main energy releasing pathway in most human cells Continues in the mitochondrion where oxygen serves as the final electron acceptor 1 glucose + 6 oxygen  6 carbon dioxide +6 water 36 or 38 ATPs are produced (total after all cycles: glycolysis, krebs and ETC) Anaerobic- without oxygen Fermentation pathway and anaerobic electron transport- many bacteria and humans, when oxygen is limited, use this pathway Ends in the cytoplasm where other substances besides oxygen is the final electron receptor Only 2 ATP are produced

8. Gluconeogenesis During starvation (not eating for 16 hours plus), the brain can use ketone bodies for energy by converting to Acetyl CoA, usually gluconeogenesis creates glucose when glycogen stores are depleted Synthesis of glucose from 3-4 carbon precursors is a reversal of glycolysis 2 pyruvate + 2 NADH + 4 ATP + 2 GTP glucose + 2 NAD+ + 4 ADP + 2 GDP + 6 Pi

9. Gluconeogenesis 3 reactions in glycolysis are essentially irreversible, thus they are bypassed in gluconeogenesis: Hexokinase (1) Phosphofructokinase (3) Pyruvate Kinase (10) Share 7 of the 10 steps in glycolysis

10. Fed state Cytoplasm All cells Fasting state Cytoplasm Liver mostly, but also kidney Glycolysis vs Gluconeogenesis

11. Activation of Pyruvate Before the Kreb’s cycle begins, pyruvate must be activated into acetyl CoA Pyruvate dehydrogenase complex (PDHC) is an enzyme that catalyzes the oxidative decarboxylation of pyruvate to acetyl CoA PDHC is a multi-enzyme comprising of 5 coenzymes- which include many vitamins such as thiamin (thiamin pyrophosphate), riboflavin (FAD), and niacin (NAD)

12. Krebs Cycle Also known as the citric acid cycle or tricarboxylic acid (TCA) cycle Under aerobic conditions pyruvate enters the mitochondria MATRIX and is oxidized to Acetyl CoA which enters the Krebs cycle Krebs cycle can occur after glycolysis, after Beta oxidation or protein degradation to provide energy for cellular respiration Equation for Krebs cycle with the beginning products and the ending. 8 steps involved 2 pyruvate + 2 GDP + 2 H3PO4 + 4 H2O + 2 FAD + 8 NAD+ ----> 6 CO2 + 2 GTP + 2 FADH2 + 8 NADH

13. Krebs Cycle http://highered.mcgraw- hill.com/sites/0072507470/student_view0/chapter25/animation__ho w_the_krebs_cycle_works__quiz_1_.html http://highered.mcgraw- hill.com/sites/0072507470/student_view0/chapter25/animation__ho w_the_krebs_cycle_works__quiz_1_.html

14. Summary TCA Occurs in the mitochondrial matrix Uses acetyl CoA to produce: 3 NADH, 1 FADH, 1 GTP, 2CO 2 Produce intermediates for biosynthetic pathways such as aminoacid synthesis, gluconeogenesis, pyrimidine synthesis, phorphyrin synthesis, fatty acid synthesis, isoprenoid synthesis.

15. Electron Transport Chain (ETC) Final pathway by which electrons generated from oxidation of carbs, protein and fatty acids, are ultimately transferred to O 2 to produce H 2 0 Located in the inner mitochondrial membrane Electrons travel down the chain, pumping protons into the intermembrane space creating the driving force to produce ATP in a process called oxidative phosphorylation There are 4 complexes that comprise the ETC

16. Electron Transport Chain http://vcell.ndsu.edu/animations/etc/movie.htm

17. Summary ETC Reduced electron carriers NADH & FADH 2 reduce O 2 to H 2 O via the ETC. The energy released creates a proton gradient across the inner mitochondrial membrane. The protons flow down this concentration gradient back across the inner mitochondrial membrane through the ATP Synthase. The driven force makes this enzyme rotate and this conformation generates enough energy to make ATP. Oxidation of NADH to NAD+ pumps 3 protons which charges the electrochemical gradient with enough potential to generate 3 ATPs. Oxidation of FADH2 to FAD+ pumps 2 protons which charges the electrochemical gradient with enough potential to generate 2 ATPs.