1. Biology, 9th ed,Sylvia Mader
Chapter 06
Metabolism
Lecture 2
Enzymes

2. Metabolism Cells break down organic molecules to generate energy (ATP)
Energy is used for: growth, cell division, contraction, secretion, and other functions
Metabolism is all the chemical reactions that occur in an organism
Chemical reactions provide energy and maintain homeostasis:
metabolic turnover
growth and cell division
special processes, such as secretion, contraction, and action potential propagation

3. Metabolism
Metabolic reactions could be either catabolic (catabolism) or anabolic (anabolism)
Anabolism
Anabolism is the formation of new chemical bonds to produce new organic molecules
New Organic molecules are needed for/to:
Performance of structural maintenance and repairs
Support of growth
Production of secretions
Building of nutrient reserves

4. Metabolism Catabolism
Catabolism is the metabolic reactions that breaks down organic substrates in order to release energy
Catabolic reactions occur in series of steps
Catabolic reactions generate energy by breaking down large molecules to small molecule
Small molecules enter Mitochondria to release more energy

5. Cells and Mitochondria
Cells provide small organic molecules for their mitochondria
Mitochondria produce ATP that is used by the cell to perform cellular functions i.e. cells feed mitochondria nutrient and in return mitochondria provide the cells with energy (ATP).
Mitochondria accept only specific organic molecules e.g. Pyruvic Acid, acetyl coenzyme A
Large organic nutrients (e.g. Glucose) are broken down into smaller fragments (e.g. Pyruvic Acid) in the cytoplasm, before they could enter mitochondria

6. Cells and Mitochondria
Mitochondria breaks down the molecules to carbon dioxide, water, and generates more energy (ATP) via two pathways:
1.  TCA cycle
2. Electron transport system (ETS)

7. Carbohydrate Metabolism
Glycolysis is the process of breakdown of glucose into pyruvic acid
Glycolysis occur in the cytoplasm and it requires:
One molecule of glucose + 2 ATP + 4ADP + 2NAD + inorganic phosphate + cytoplasmic enzymes
Glycolysis generates:
Two pryruvic acid + 4ATP +2ADP + 2NADH
The net gain of ATP of glycolysis is 2ATP (it produces 4ATP but two of the ATP are used)

8. Carbohydrate Metabolism
Aerobic metabolism (cellular respiration)
Pyruvic acid will enter mitochondria and generate more ATP via TCA cycle and ETS
Two pyruvates = 34 ATP
The chemical formula for this process is C6H12O6 + 6 O2  6 CO H2O
Anaerobic metabolism (fermentation)
In the absence of oxygen pyruvic acid will not enter mitochondria
Pyruvic acid will go through the process of anaerobic respiration and will be converted into Lactic acid
This process dose not generate any ATP

9. Glycolysis: Steps in Glycolysis
Glucose (a 6 carbon molecule) enters the cell
As soon as glucose is inside the cell, a phosphate is added to carbon number 6, and the new molecule is called glucose 6 phosphate. This reaction is called phosphorylation and it requires one ATP, enzyme called hexokinase.
Glucose 6 phosphate goes through the second phosphorylation reaction and a phosphate is added to carbone number 1. The new molecule produced as a result is called Fructose 1,6 Bisphosphate
The Fructose 1,6 bisphosphate (6 carbon molecule with phosphates attached to carbon 1 and carbon 6) will split into two 3 carbon molecule:
Glyceraldehyde 3 phosphate
Dihydroxyacetone
Each 3 carbon molecule will become a pyruvic acid through number of steps (see the diagram on the left)

10. Mitochondrial ATP Production (cellular respiration)
The two pyruvic acid molecules will enter mitochondria
In the mitochondria pyruvic acid will join Coenzyme A (CoA) to form acetyl CoA before entering the TCA cycle.
TCA cycle will break down pyruvic acid completely
Decarboxylation
Hydrogen atoms passed to coenzymes
Oxidative phosphorylation

11. The TCA Cycle Steps
Pyruvic acid combine with coenzyme A to form acetyl coenzyme A. This reaction releases NADH and carbon dioxide
Acetyl is a 2 carbon molecule. Acetyl-coenzyme A will give the two carbon molecule (acetyl) to the 4 carbon molecule (oxaloacetic acid)
The 4 carbon molecule will become a 6 carbon molecule (citric acid)
Citric acid will go through number of steps and will become back a 4 carbon molecule .
The TCA cycle will begin with formation of citric acid and end with formation of oxaloacetic acid.
The TCA cycle will run twice for one molecule of glucose, because one molecule of glucose produces two pyruvic acid and each pyruvic acid turns once cycle
7) Each cycle of TCA will generate 3NADH, 1FADH2, and 1GTP
NADH and FADH2 will enter the electron transport system and generate ATP
One NADH = 3ATP and one FADH2 = 2ATP (see ETS)

12. The TCA Cycle
Pyruvic acid (a 3 carbon molecule) requires NAD and Coenzyme to form Acetyl coenzyme A
This reaction will generate NADH, carbon dioxide and acetyl coenzyme A. Notice that pyruvic acid is a 3 carbon molecule , in this reaction one of the carbons was released as carbon dioxide is formed and two carbon is left as a acetyl
Acetyl coenzyme A will transfer the acetyl to oxaloacetic (a 4 carbon molecule) acid and coenzyme A will becomee free. 4 carbon molecule from oxaloacetic acid and two carbon from acetyl will generate a 6 carbon molecule (citric acid)
The free coenzyme A will be reused by another pyruvic acid.
Citric acid will go through number of steps (e.g. it will become isocetric acid then ketoglutaric acid and so on)and eventually will become oxaloacetic acid

13. The TCA Cycle
Citric acid will go through number of steps (e.g. it will become isocetric acid then ketoglutaric acid and so on)and eventually will become oxaloacetic acid

14. Oxidative phosphorylation and the ETS
Requires coenzymes and consumes oxygen
Key reactions take place in the electron transport system (ETS)
Cytochromes of the ETS pass electrons to oxygen, forming water
The basic chemical reaction is: H2 + O2  2 H2O

15. Electron Transport System (ETS)
ETS is sequence of proteins called cytochromes
Each cytochrome has:
A protein - embedded in the inner membrane of a mitochondrion,
A pigment

16. Electron Transport System (ETS)
STEP1: coenzyme strips a pair of hydrogen atoms from a substrate molecule.
STEP2: NADH and FADH2 deliver hydrogen atoms to coenzymes embedded in the inner membrane of a mitochondrion.
STEP3: Coenzyme Q accepts hydrogen atoms from FMNH2 and FADH2 and passes electrons to cytochrome b.
STEP4: Electrons are passed along the electron transport system, losing energy in a series of small steps. The sequence is cytochrome b to c to a to a3.
STEP5: At the end of the ETS, an oxygen atom accepts the electrons, creating an oxygen ion (O–). This ion has a very strong affinity for hydrogen ions (H+); water is produced.

17. Oxidative Phosphorylation

18. Energy yield of glycolysis and cellular respiration
Per molecule of glucose entering these pathways
Glycolysis – has a net yield of 2 ATP
Electron transport system – yields approximately 28 molecules of ATP
TCA cycle – yields 2 molecules of ATP

19. The Energy Yield of Aerobic Metabolism

20. The Energy Yield of Aerobic Metabolism

21. The Energy Yield of Aerobic Metabolism

22. The Energy Yield of Aerobic Metabolism

23. The Energy Yield of Aerobic Metabolism

24. The Energy Yield of Aerobic Metabolism

25. The Energy Yield of Aerobic Metabolism

26. A Summary of the Energy Yield of Aerobic Metabolism

27. Synthesis of glucose and glycogen
Gluconeogenesis
Synthesis of glucose from noncarbohydrate precursors such as lactic acid, glycerol, amino acids
Liver cells synthesis glucose when carbohydrates are depleted
Glycogenesis
Formation of glycogen
Glucose stored in liver and skeletal muscle as glycogen
Important energy reserve

28. Key Concepts Process Location Molecules produced ATP NADH FADH CO2
Glycolysis
cytoplasm 4 2
Fermentation/anaerobic respiration
Transition/Intermediate steps (Pyruvate to Acetyl CoA)
Mitochondria 1
TCA 3
ETS
Mitochondria (inner Mitochondrial Membrane
NADH = 3ATP
FADH2 = 2ATP

29. Carbohydrate Breakdown and Synthesis

30. Lipid catabolism Lipolysis
Lipids broken down into pieces that can be converted into pyruvate
For example triglycerides are split into glycerol and fatty acids
Glycerol enters glycolytic pathways
Fatty acids enter the mitochondrion

31. Lipid catabolism Beta-oxidation Lipids and energy production
Breakdown of fatty acid molecules into 2-carbon fragments
Lipids and energy production
Used when glucose reserves are limited

32. Beta Oxidation
In beta oxidation long chain of fatty acids are broken down into fragments of two carbons.
Say we have a fatty acid chain that is 18 carbon long. During beta oxidation fragments of two carbon will be removed from the chain of fatty acid. So after the first round of reaction (as shown in the figure) a fatty acid chain that is 16 carbon long will remain, after the second round of reactions a fatty acid chain that 14 carbon long will remain
For each round of reaction two carbon will be removed from the chain. As two carbons are removed from the chain, NADH, FADH2 and Acetyl CoA will be generated.
The steps in beta oxidation:
Coenzyme A bind to fatty acid. This step requires one ATP
2) This reaction will prepare fatty acid for beta oxidation and generate a fatty acid attached to CoA

33. Beta Oxidation
3) The first round of beta oxidation will generate one NADH, one FADH2 and one Acetyl CoA
4) Acetyl CoA will enter TCA cycle and generate 3NADH, 1FADH and 1GTP. 3NADH = 9ATP, 1FADH2 = 2ATP, and GTP = 1ATP.

34. Beta Oxidation NADH and FADH2 will enter the ETS and generate ATP
1NADH = 3ATP
1FADH2 = 2ATP
Summary :
one round of beta oxidation will generate :
NADH = 3ATP
FADH2 = 2ATP
Acetyl CoA = 12ATP
So if each round of beta oxidation produces 17ATP, then one molecule of fat will produce a lot more ATP (energy) than one molecule of glucose. Remember that glucose produced 2ATP in glycolysis and 34/36ATP via TCA and ETS

35. Protein Metabolism Amino acid catabolism
If other sources inadequate, mitochondria can break down amino acids
TCA cycle
The first step in amino acid catabolism is the removal of the amino group (-NH2)
The amino group is removed by transamination or deamination
Transamination – attaches removed amino group to a keto acid
Deamination – removes amino group generating NH4+
Proteins are an impractical source of ATP production

36. Oxidation, Reduction, and Energy Transfe
Enzymatic steps of oxidative phosphorylation involve oxidation and reduction
The loss of electrons is oxidation; the acceptance of electrons is reduction
Electron donor is oxidized (loss energy) and electron recipient reduced (gain energy)
Reduced molecule does not acquire all the energy released by oxidized molecule – thus some energy is released as heat, and formation of ATP
Coenzyme acts as intermediary that accepts electrons from one molecule and transfer it to another
In Kreb Cycle NAD and FAD remove hydrogen atoms from organic substrates
NADH and FADH2, the reduced forms of NAD and FAD, transfer their hydrogen to other coenzymes
Protons are released, and the electrons, which carry the chemical energy, enter a sequence of oxidation–reduction reactions