1. NS 315 Unit 4: Carbohydrate Metabolism
Penni Davila Hicks, PhD, RD,LD
Kaplan University

2. Objectives We want to learn about:
Review carbohydrate digestion/absorption
Glycolysis
Gluconeogenesis
Krebs Cycle
Electron Transport Chain 2 2

3. Definitions
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 3

4. Definitions
Pyruvate: final 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 4 4

6. Importance of Glucose Carbohydrates are broken down to simplest form
Polysaccharides to monosaccharides or glucose
Glucose is essential for our survival
Especially for:
Brain
Central Nervous System
Red Blood Cells

7. Glycogenesis
Synthesis of glycogen from excess glucose that takes place in liver and muscle.
Liver is the major site of glycogen synthesis and storage
Liver plays an important role in maintaining blood glucose
Muscle stores most of the glycogen in the body and used at time of physical exertion (no synthesis here)
When blood glucose is high insulin stimulates glycogenesis
Glycogen if vitally important in ensuring a reserve of instant energy
Synthesis of a linear and branched glucose polymer (glycogen) from excess glucose in liver and muscle.

8. Glycogenolysis Breakdown of glycogen into glucose
At times of energy demands
Takes place in liver and muscle
Regulated by glucagon
Glucose from liver can be used to maintain blood glucose levels and to produce energy or ATP

9. Glycolysis
The breakdown or oxidation of glucose to two pyruvate molecules that occurs in the cytosol.
The metabolic fate of pyruvate is different under aerobic conditions and anaerobic conditions.
Aerobic conditions – pyruvate enter the Krebs cycle to produce ATC
Anaerobic conditions – pyruvate is converted to lactate

10. 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
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 10

11. Pathways during Glycolysis
Anaerobic- without oxygen
Aerobic -
with oxygen available to the cells
Pyruvate → mitochondria
The main energy releasing pathway in most human cells
36 or 38 ATPs are produced (total after all cycles: glycolysis, krebs and ETC)
Fermentation pathway and anaerobic electron transport- many bacteria and humans, when oxygen is limited, use this pathway
Only 2 ATP are produced
Pyruvate enters mitochondria for complete oxidation 11 11

12. Gluconeogenesis Synthesis of glucose from non-carbohydrate precursors,
amino acids, lactate & glycerol,
occurs in both the mitochondria and cytosol of the liver (and to some extent the kidney during starvation)
Gluconeogenesis is a reversal of glycolysis
2 pyruvate + 2 NADH + 4 ATP + 2 GTP glucose + 2 NAD+ + 4 ADP + 2 GDP + 6 Pi 12 12

13. Gluconeogenesis
During starvation (not eating for 16 hours or more), the brain can use ketone bodies from glycerol for energy by converting to Acetyl CoA
Usually gluconeogenesis creates glucose when glycogen stores are depleted
2 pyruvate + 2 NADH + 4 ATP + 2 GTP glucose + 2 NAD+ + 4 ADP + 2 GDP + 6 Pi 13 13 13

14. 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 14 14

15. Glycolysis vs Gluconeogenesis
Fed state
Glucose→Pyruvate
Cytoplasm
All cells
Fasting state
Cytoplasm
Liver mostly, but also kidney
Non-carb source → Glucose 15 15

16. Krebs Cycle Acetly Co A begins the 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
Acetly Co A begins the Krebs cycle

17. * *

18. Activation of Pyruvate
First step activates pyruvate to acetyl CoA.
Pyruvate Dehydrogenase Complex (PDHC) catalyzes the oxidative decarboxylation of pyruvate to acetyl CoA
PDHC is a multienzyme comprising of 5 coenzymes (some vitamins): thiamin pyrphosphate (thiamin), CoA, lipoic acid, FAD (riboflavine) and NAD (niacin)

19. PDHC

20. Summary TCA Occurs in the mitochondrial matrix
Uses acetyl CoA to produce ATP
NADH, FADH2, 2Co2
Produce intermediates for biosynthetic pathways such as amino acid synthesis, gluconeogenesis, pyrimidine synthesis, phorphyrin synthesis, fatty acid synthesis

21. Electron Transport Chain (ETC)
Final pathway by which electrons generated from oxidation of carbs, protein and fatty acids, are ultimately transferred to O2 to produce H20
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
We can make ATP from ATP

22. Summary ETC
Reduced electron carriers NADH & FADH2 reduce O2 to H2O 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.