1. Lecture 25: Metabolism and Energetics
Lecturer: Dr. Barjis
Room: P313
Phone: (718)

2. Learning Objectives
Explain why cells need to synthesis new organic components
Describe the basic steps in glycolysis, the TCA cycle, and the electron transport chain
Summarize the energy yield of glycolysis and cellular respiration
Describe the pathways involved in lipid, protein and nucleic acid metabolism

3. Learning Objectives
Summarize the characteristics of the absorptive and postabsorptive metabolic states
Explain what constitutes a balanced diet and why such a diet is important
Define metabolic rate and discuss the factors involved in determining an individual’s BMR

4. 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

5. An Introduction to Cellular Metabolism

6. 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

7. 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

8. 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, fatty acid, amino acids) are broken down into smaller fragments (e.g. Pyruvic Acid) in the cytoplasm

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

10. Nutrient Use in Cellular Metabolism

11. Carbohydrate Metabolism
Most cells generate ATP through the breakdown
of carbohydrates
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)

12. Carbohydrate Metabolism
Most cells generate ATP through the breakdown
of carbohydrates
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

13. 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 carbonenumber 1. The new molecule produced as a result is called Fructose 1,6 Bisphosphate
The Fructose 1,6 bisphosphate (6 carbon molecule with phosphate s 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)

14. 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

15. 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)

16. 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

17. The TCA Cycle
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

18. 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

19. 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

20. 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.

21. Oxidative Phosphorylation

22. 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

23. The Energy Yield of Aerobic Metabolism

24. The Energy Yield of Aerobic Metabolism

25. The Energy Yield of Aerobic Metabolism

26. The Energy Yield of Aerobic Metabolism

27. The Energy Yield of Aerobic Metabolism

28. The Energy Yield of Aerobic Metabolism

29. The Energy Yield of Aerobic Metabolism

30. The Energy Yield of Aerobic Metabolism

31. The Energy Yield of Aerobic Metabolism

32. A Summary of the Energy Yield of Aerobic Metabolism

33. 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

34. Carbohydrate Breakdown and Synthesis

35. 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

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

37. 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

38. 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.

39. 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

40. Lipid synthesis (lipogenesis)
Non essential fatty acids are the fatty acids that can be synthesized
Essential fatty acids are fatty acid that cannot be synthesized and must be included in diet
Example of essential fatty acids include:
Linoleic and linolenic acid

41. Lipid Synthesis

42. Lipid transport and distribution
Lipoproteins are lipid-protein complex that contains large glycerides and cholesterol
5 types of lipoprotein
1) Chylomicrons
Largest lipoproteins composed primarily of triglycerides
Delivers lipids from digestive tract (intestine) to liver
2) Very low-density lipoproteins (VLDLs)
Contain triglycerides, phospholipids and cholesterol
Delivers triglycerides to the cells
Lipoprotein lipase (enzyme) in the capillaries break the triglyceride into monoglyceride and fatty acid for use by the cell
Steps:
VLDL containing triglyceride is released into blood circulation by the liver
When VLDL gets to the capillaries, an enzyme called lipase break the triglycerides into monglyceride and free fatty acid
The monoglyceride and free fatty acid are used by the cell
VLDL is left with less triglyceride so it is called IDL

43. Lipid transport and distribution
3) Intermediate-density lipoproteins (IDLs)
Contain smaller amounts of triglycerides
Return remaining triglycerides back to the liver
When the IDL arrives into the liver, the livers adds cholesterol to IDL. Once cholesterol is added to the IDL, it would be called LDL
4) Low-density lipoproteins (LDLs) – also called the bad cholesterol
Contain mostly cholesterol
LDL is released into the blood stream by the liver
LDL delivers cholesterol to the cells
The cell uses the cholesterol for synthesis of membrane, hormones and other material
Any excess cholesterol that is not used by the cell will diffuse out of cell back into capillaries (circulation)
5) High-density lipoproteins (HDLs) also called the good cholesterol
HDL collects the extra cholesterol that diffuses out of the cell and delivers them back to the liver
The liver reuses the cholesterol to make LDL, and excretes any excess cholesterol with bile

44. Lipid Transport and Utilization

45. Lipid Transport and Utilization

46. 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

47. Amino Acid Catabolism: Transamination
Attaches the amino group of an amino acid to a keto acid
  Transamination converts the keto acid into an amino acid that can enter the cytosol and be used for protein synthesis
Reactions enable a cell to synthesize many of the amino acids needed for protein synthesis

48. Amino Acid Catabolism: Deamination
Deamination preparing an amino acid for breakdown in the TCA cycle
Deamination removes an amino group of an amino acid and enerates an ammonia (NH3) molecule or an ammonium ion (NH4+).
Ammonia molecules are highly , thus liver (the primary site of deamination) has enzymes that converts the ammonia to urea

49. Amino Acid Catabolism

50. Protein synthesis Essential amino acids
Cannot be synthesized by the body in adequate supply
Nonessential amino acids
Can be synthesized by the body via amination
Addition of the amino group to a carbon framework

51. Nucleic acid metabolism
Nuclear DNA is never catabolized for energy
RNA catabolism
RNA molecules are routinely broken down and replaced
Generally recycled as nucleic acids
Can be catabolized to simple sugars and nitrogenous bases
Do not contribute significantly to energy reserves

52. Body has five metabolic components
Liver
The focal point for metabolic regulation and control
Adipose tissue
Stores lipids primarily as triglycerides
Skeletal muscle
Substantial glycogen reserves

53. Body has five metabolic components
Neural tissue
Must be supplied with a reliable supply of glucose
Other peripheral tissues
Able to metabolize substrates under endocrine control

54. Vitamins
Are needed in very small amounts for a variety of vital body activities
Fat soluble
Vitamins A, D, E, K
Taken in excess can lead to hypervitaminosis
Water soluble
Not stored in the body
Lack of adequate dietary intake = avitaminosis

55. You should now be familiar with:
Why cells need to synthesis new organic components
The basic steps in glycolysis, the TCA cycle, and the electron transport chain
The energy yield of glycolysis and cellular respiration
The pathways involved in lipid, protein and nucleic acid metabolismBMR

56. You should now be familiar with:
The characteristics of the absorptive and postabsorptive metabolic states
What constitutes a balanced diet and why such a diet is important
Metabolic rate and the factors involved in determining an individual’s BMR