12 - Bioenergetics
12 - Bioenergetics
12 - Bioenergetics
Module 9
Bioenergetics
Instructor: ________________________
Email:________________________________
Virtual Consultation time:____________________________
Introduction
Living organisms need to process the food before it can be utilized by the body. There are many
biochemical processes that occur simultaneously inside the cell in order to cope with the biological
demand. In this module, metabolism will be discussed, giving emphasis on glucose metabolism, citric acid
cycle and oxidative phosphorylation.
Course Outcomes:
1. Explain how living organisms extract energy from the surroundings to perpetuate life
2. Explain how chemical reactions are regulated inside the living cell
3. Apply key concepts in biochemistry to explain its practical applications in the field of nutrition,
agriculture, medicine, pharmacy and allied fields
Learning Outcomes:
1. Understand the importance of enzymes in metabolism
2. Differentiate catabolism from anabolism
3. Identify the different catabolic and anabolic pathways
4. Explain how ATP is produced in from metabolites of catabolism and electron transport chain
5. Compute for the net ATP formed from a given biomolecule
Quick Test:
Classify the following chemical reactions as catabolic or anabolic
a) Synthesis of nucleotide from a nucleoside and phosphate
b) Hydrolysis of a trisaccahride to form three monosaccharides
c) Formation of triacylglycerol from glycerol and fatty acids
d) Breaking down of pentasaccharide into five monosaccharides
Answer:
a) Anabolic: Subunits are combined to form a larger unit
b) Catabolic. A complex unit is broken down to its simple units
c) Anabolic. A larger unit is assembled from its smaller subunits
d) Catabolic. 5 simple compounds were produced by breaking down a larger compound
Bettelheim, F., Brown, W.,Campbell, M.K., Farell, S. Torres, O. 2013. Introduction to General, Organic, and Biochemistry, 10th Edition. 2
Brooks/Cole, Cengage Learning
Stephen Stoker, H. 2010. General, Organic, and Biological Chemistry, 5th Edition. Brooks/Cole, Cengage Learning
The food that we eat undergoes a series of biochemical reactions in order for our body
to utilize them. These macromolecules are largely converted into energy that fuels our daily
activities such as walking, breathing and thinking. Even biological functions at the molecular
level, e.g. DNA replication, protein synthesis, cell repair are energy demanding processes. To
generate energy from the food, the body uses different catabolic pathways for each type of
compound. All these pathways are congregated to one common catabolic pathway. Common
catabolic pathway is consists of the 1) Tricarboxylic Acid cycle, also known as the citric acid
cycle or the Krebs cycle and the 2) oxidative phosphorylation. The conversion of food to energy
can be summarized into four steps:
c4 c6
Stage 3:
c4 c6 The converted biomolecules
enters the common catabolic
pathway. The first phase is the
c4 Citric Acid Cycle
c5 Citric Acid Cycle. NADH and
FADH2 are produced in this
phase.
c4 c4
Stage 3:
NAD
The NADH and FADH2 are
ATPase ATP
H Electron Transport Chain utilized in the oxidative
FADH phosphorylation. Oxidative
2
phosprylation consists of the
Oxidative Phosphorylation
Electron transport Chain and
the Phosphorylation. More
Figure 8.1 Overview on the metabolic pathway of glucose to ATP ATPs are produced
Bettelheim, F., Brown, W.,Campbell, M.K., Farell, S. Torres, O. 2013. Introduction to General, Organic, and Biochemistry, 10th Edition. 3
Brooks/Cole, Cengage Learning
Stephen Stoker, H. 2010. General, Organic, and Biological Chemistry, 5th Edition. Brooks/Cole, Cengage Learning
Figure 8.4 Diagram of a mitochindrion
source: Bettelheim, F . et.al. 2013. p.756
Figure 8.3 General representation of an animal cell.
Source: Stephen Stoker. H. 2010. p779
It is a common knowledge that the mitochondrion is called the powerhouse of the cell. The
common metabolic pathway occurs in the mitochondrion and most ATPs are produced.
3) The protein complexes involved in the oxidative phosphorylation are embedded in the inner
membrane.
Outer membrane
ATPase
Electron Transport Chain Inner membrane
Figure 8.5 Simplified representation of the mitochondria and the location of oxidative phosphorylation
Bettelheim, F., Brown, W.,Campbell, M.K., Farell, S. Torres, O. 2013. Introduction to General, Organic, and Biochemistry, 10th Edition. 4
Brooks/Cole, Cengage Learning
Stephen Stoker, H. 2010. General, Organic, and Biological Chemistry, 5th Edition. Brooks/Cole, Cengage Learning
SUBTOPIC 8.2: GLYCOLYSIS Refer to chapter 28 of your book
Glucose
Fructose-
6-phosphate
ATP
3 Energy is CONSUMED
ADP
Fructose-
1,6-
bisphosphate
NOTE:
4
This two sugars are isomers. Since
glyceraldehyde-3-phosphate is utilized
further in glycolysis,
Dihydroxyacetone Glyceraldehyde- dihydroxyacetonephosphate is always
Phosphate **** 3-phosphate converted into gl-3-phosphate. Therefore,
the second phase happens twice and
product yield is doubled.
5 SECOND PHASE
NAD + Pi 3-Carbon Stage
The compounds
NADH + H+
involved in this
1,3-Bisphosphoglycerate stage contain 3
carbons.
ADP Energy is PRODUCED
Energy is
6
ATP produced
3-phosphoglycerate
2-phosphoglycerate
8 H2O
Phosphoenol pyruvate
ADP
Energy is PRODUCED
9
Figure 8.6 Schematic ATP
diagram of glycolysis
pyruvate
Bettelheim, F., Brown, W.,Campbell, M.K., Farell, S. Torres, O. 2013. Introduction to General, Organic, and Biochemistry, 10th Edition. 5
Brooks/Cole, Cengage Learning
Stephen Stoker, H. 2010. General, Organic, and Biological Chemistry, 5th Edition. Brooks/Cole, Cengage Learning
STEP KEY PROCESSES ENZYME INVOLVED
1)Phosphorylation -Phosphate is added to the glucose molecule,
forming glucose-6-phosphate Hexokinase:
glucokinase
-Phosphate is taken from an ATP molecule;
therefore, an energy is consumed. Hexokinase requires
Mg2+ ion for its activity.
Bettelheim, F., Brown, W.,Campbell, M.K., Farell, S. Torres, O. 2013. Introduction to General, Organic, and Biochemistry, 10th Edition. 6
Brooks/Cole, Cengage Learning
Stephen Stoker, H. 2010. General, Organic, and Biological Chemistry, 5th Edition. Brooks/Cole, Cengage Learning
9) Phosphorylation - phosphoenolpryuvate transfers its high-
of ADP energy phosphate to ADP Pyruvate kinase
-an ATP molecule is formed
-pyruvate is produced
The net overall equation for the process of converting glucose to pyruvate:
For every molecule of glucose, 2 molecules of pyruvates, 2 NADH, 2 ATP, 2H and 2 H2O
are produced
Because of the cleaving (step 4) and the isomerization of the triose sugar (****), the
second phase of glycolysis is repeated. Hence, the amount of products is doubled.
Even though a total of 4 ADPs are used in phase 2 (step 6 & 9), 2ADPs are produced in
phase 1. There is a net usage of 2ADP
Pyruvate has three common fates after it has been generated by glycolysis. In the
section above, pyruvate enters the citric acid cycle after it is converted into Acteyl CoA.
However, pyruvate is also converted into lactate and ethanol in certain conditions:
B
C
lactate pyruvate Ethanol + Co2
NAD NAD
NADH + H +
NAD NADH + H+
A
NADH + H+
A Pyruvate is converted to acetyl CoA and enters the citric acid cycle
Pyruvate undergoes oxidative decarboxylation in the presence of
Coenzyme A (CoA-- SH)
The enzyme involved is Pyruvate dehydrogenase
Proceeds under aerobic conditions (oxygen-rich)
Acetyl CoA and CO2 are produced in this process. Only Acetyl CoA
enters the Citric Acid Cycle.
Bettelheim, F., Brown, W.,Campbell, M.K., Farell, S. Torres, O. 2013. Introduction to General, Organic, and Biochemistry, 10th Edition. 7
Brooks/Cole, Cengage Learning
Stephen Stoker, H. 2010. General, Organic, and Biological Chemistry, 5th Edition. Brooks/Cole, Cengage Learning
C Pyruvate is converted to ethanol
Common in some microorganisms
Common in yeast and is the primary mechanism behind bread
leavening, beer and wine fermentation
The net overall reaction for processing glucose to acetyl CoA is:
Glucose + 4NAD+ 2ADP + 2Pi+ 2 CoA-SH 2 acetyl CoA + 4NADH + 2ATP + 4H +2H2+ 2CO2
Regulation of Glycolysis 3
3) Pyruvate kinase- High levels of ATP signals the inhibition of the enzyme pyruvate kinase.
Glycolysis discussion:
https://www.youtube.com/watch?v=ArmlWtDnuys
Regulation of glycolysis:
https://www.youtube.com/watch?v=TxDC0aHjsU4
Bettelheim, F., Brown, W.,Campbell, M.K., Farell, S. Torres, O. 2013. Introduction to General, Organic, and Biochemistry, 10th Edition. 8
Brooks/Cole, Cengage Learning
Stephen Stoker, H. 2010. General, Organic, and Biological Chemistry, 5th Edition. Brooks/Cole, Cengage Learning
SUBTOPIC 8.3: β-Oxidation of Fatty Acids Refer to chapter 28 of your book
Triacylglycerols (TAGs) are stored mainly in the adipose tissue by the cell adipocyte. Dietary
TAGs stored in the adipose tissue need to undergo a series of hydrolysis in order for the body to
use it. The hydrolysis of TAGs followed by its release into the bloodstream as fatty acids and
glycerol is called the Triacylglycerol mobilization.
In order for the body to utilize the stored fats in the adipose tissue, mobilizes the TAGs
through a series of hydrolysis.
The use of TAGs in energy production is triggered by several hormones including
Epinephrine
The interaction of hormones with the adipocyte receptor triggers the production of cAMP,
which eventually stimulates the activation of Hormone-Sensitive Lipase (HSL). HSL is
needed in the hydrolysis of TAGs
The hydrolysis of TAGs produces Fatty acids and glycerol which are released into the
bloodstream
Glycerol, once released into the bloodstream, travels to the kidney and liver and is
converted into dihyroxyacetone phosphate.
Dihyroxyacetone phosphate is an intermediate in both glycolysis and gluconeogenesis
(production of glucose)
The Fatty Acids undergo the process of β-oxidation which produces Acetyl CoA, FADH2
and NADH.
Bettelheim, F., Brown, W.,Campbell, M.K., Farell, S. Torres, O. 2013. Introduction to General, Organic, and Biochemistry, 10th Edition. 9
Brooks/Cole, Cengage Learning
Stephen Stoker, H. 2010. General, Organic, and Biological Chemistry, 5th Edition. Brooks/Cole, Cengage Learning
Conversion of free fatty acids can be divided into three parts: 1) Activation of the fatty acid
by coenzyme A, 2) Transportation of the fatty acid into the matrix by a shuttle system and 3)
β-oxidization of fatty acids to produce Acetyl CoA, FADH2 and NADH.
Bettelheim, F., Brown, W.,Campbell, M.K., Farell, S. Torres, O. 2013. Introduction to General, Organic, and Biochemistry, 10th Edition. 10
Brooks/Cole, Cengage Learning
Stephen Stoker, H. 2010. General, Organic, and Biological Chemistry, 5th Edition. Brooks/Cole, Cengage Learning
β -oxidation Pathway
Step 1: Oxidation (dehydrogenation)
Alkane
Enzyme: Thiolase
Acyl CoA with A shorter Acyl CoA is produced and an Acetyl CoA
two carbons
The shorter Acyl CoA repeats step 1 until it is
fewer
completely oxidized to Acetyl CoA
Video Animation:
Fatty Acid Oxidation Overview: https://www.youtube.com/watch?v=acA5iF1zrDI
Fatty Acid Oxidation Part 1: https://www.youtube.com/watch?v=epABNPUtkVc&t=6s
Fatty Acid Oxidation Part 2: https://www.youtube.com/watch?v=ITPKSc5NrQQ
Bettelheim, F., Brown, W.,Campbell, M.K., Farell, S. Torres, O. 2013. Introduction to General, Organic, and Biochemistry, 10th Edition. 11
Brooks/Cole, Cengage Learning
Stephen Stoker, H. 2010. General, Organic, and Biological Chemistry, 5th Edition. Brooks/Cole, Cengage Learning
SUBTOPIC 8.4: CITRIC ACID CYCLE Refer to chapter 27 of your book
Acetyl CoA
CoA
C2
1
Citrate
C6 2
Oxalo-
acetate
C4 Iso-
citrate
NADH
8 C6
NAD
3 NAD
Malate NADH +
H+
C4
α-keto
glutarate
7
C5
CoA
Fumarate 4 NAD + Pi
C4 NADH +
Succinyl
6 CoA H+
Succinate
FADH2 C4
C4 5
FAD CO2
GDP
CoA GTP
Figure 8.10 The Tricarboxylic Acid Cycle also known as Citric Acid Cycle or Krebs Cycle
Bettelheim, F., Brown, W.,Campbell, M.K., Farell, S. Torres, O. 2013. Introduction to General, Organic, and Biochemistry, 10th Edition. 12
Brooks/Cole, Cengage Learning
Stephen Stoker, H. 2010. General, Organic, and Biological Chemistry, 5th Edition. Brooks/Cole, Cengage Learning
STEPS Processes Involved Enzyme involved
1) Formation of Citrate -Acetyl CoA (2 carbons) with oxaloacetate Citrate
(4 carbons) forming Citrate (6 carbons) synthase
-The acetyl group is transferred to the
oxaloacetate and the CoA is released.
- The Acetyl CoA and oxaloacetate are
condensed to form citryl CoA. Then the
citryl CoA is hydrolyzed to form citrate while
releasing the CoA
Bettelheim, F., Brown, W.,Campbell, M.K., Farell, S. Torres, O. 2013. Introduction to General, Organic, and Biochemistry, 10th Edition. 13
Brooks/Cole, Cengage Learning
Stephen Stoker, H. 2010. General, Organic, and Biological Chemistry, 5th Edition. Brooks/Cole, Cengage Learning
The net overall reaction for citric acid cycle is:
1) ATP, NADH, NAD and ADP regulate the citric acid cycle. When ATP and NADH are
abundant, the citric acid cycle is slowed down or shut down. ATP and NADH inhibit the action of
the enzymes that catalyzes the citric acid cycle.
2) Conversely, ADP and NAD stimulate the activity of the enzymes.
Bettelheim, F., Brown, W.,Campbell, M.K., Farell, S. Torres, O. 2013. Introduction to General, Organic, and Biochemistry, 10th Edition. 14
Brooks/Cole, Cengage Learning
Stephen Stoker, H. 2010. General, Organic, and Biological Chemistry, 5th Edition. Brooks/Cole, Cengage Learning
SUBTOPIC 8.5: OXIDATIVE PHOSPHORYLATION Refer to chapter 27 of your book
In the electron transport chain, electrons and hydrogen ions pass through intermediate
carriers in order to react with molecular oxygen and ultimately produce water. NADH and FADH2
are oxidized in this process. There are 4 protein complexes and 2 electron carriers involved in
this chain.
Figure 8.11 Summary of the Flow of Electrons Through the Four Complexes
Source: GOB 5th Ed. 2010. Stoker. H.S. C&E Publishing. Inc. p799
+
Figure 8.12 Summary of the H pumped by the protein complexes
Source: GOB 5th Ed. 2010. Stoker. H.S. C&E Publishing. Inc. p801
Bettelheim, F., Brown, W.,Campbell, M.K., Farell, S. Torres, O. 2013. Introduction to General, Organic, and Biochemistry, 10th Edition. 15
Brooks/Cole, Cengage Learning
Stephen Stoker, H. 2010. General, Organic, and Biological Chemistry, 5th Edition. Brooks/Cole, Cengage Learning
Figure 8.13 Schematic Diagram of the ATP production during the oxidative phosphoryltaion
Source: GOB 5th Ed. 2010. Stoker. H.S. C&E Publishing. Inc. p802
Chemiosmotic theory states that the accumulation of protons in the intermembrane space
creates osmotic pressure.
There will be a spontaneous flow of ions from a region of high concentration to a region
of low concentration.
Because there is an accumulation of protons in the intermembrane space and less
concentration of protons inside the matrix, the protons will flow back to the matrix
The protons will pass through ATPase in order to enter the matrix.
The protons passing through the ATPase will drive the ―rotation‖ of the ATPase,
allowing the conversion of ADP to ATP.
The action of ATPase can be related to a water turbine. The flow of water makes the
turbine rotate which eventually creates energy.
Bettelheim, F., Brown, W.,Campbell, M.K., Farell, S. Torres, O. 2013. Introduction to General, Organic, and Biochemistry, 10th Edition. 16
Brooks/Cole, Cengage Learning
Stephen Stoker, H. 2010. General, Organic, and Biological Chemistry, 5th Edition. Brooks/Cole, Cengage Learning
How many ATPs are produced in every molecule of glucose?
-------------------------------------------------------------------------
References:
1
Bettelheim, F., Brown, W.,Campbell, M.K., Farell, S. Torres, O. 2013. Introduction to General,
Organic, and Biochemistry, 10th Edition. Brooks/Cole, Cengage Learning.
2
Stephen Stoker, H. 2010. General, Organic, and Biological Chemistry, 5th Edition. Brooks/Cole,
Cengage Learning
3
Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002.
Section 16.2, The Glycolytic Pathway Is Tightly Controlled. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK22395/
Bettelheim, F., Brown, W.,Campbell, M.K., Farell, S. Torres, O. 2013. Introduction to General, Organic, and Biochemistry, 10th Edition. 17
Brooks/Cole, Cengage Learning
Stephen Stoker, H. 2010. General, Organic, and Biological Chemistry, 5th Edition. Brooks/Cole, Cengage Learning