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ML 105 - Lecture - METABOLIC PATHWAYS, CATABOLISM AND ENERGY PDF
ML 105 - Lecture - METABOLIC PATHWAYS, CATABOLISM AND ENERGY PDF
Ml 105
Unit 7
METABOLIC PATHWAYS, CATABOLISM AND ENERGY
METABOLISM
Source of energy
Thermodynamics
Utilization of energy
Intermediates in lipids,
carbohydrate, nitrogen and
secondary pathways their
regulation and control
(glycolysis, TCA cycle,
phosphogluconate pathway,
glucoronic acid pathways,
oxidation/reduction and
electron transport, oxidative
phosphorylation, oxidation of
fatty acids and ketone bodies,
oxidation and degradation of
amino acids).
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Unit 7
ENERGY AND THERMODYNAMICS
METABOLISM
INTRODUCTION
The living cell is a miniature chemical factory where thousands of reactions occur
The cell extracts energy and applies energy to perform work
Some organisms even convert energy to light, as in bioluminescence
An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics
Metabolism Is the totality of an organism’s chemical reactions which rises from interactions between
molecules
Organization of the Chemistry of Life into Metabolic Pathways
A metabolic pathway begins with a specific molecule and ends with a product
Each step is catalyzed by a specific enzyme
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Unit 7
ENERGY AND THERMODYNAMICS
METABOLISM
Useful Definations
Ml 105
Unit 7 METABOLISM
METABOLISM
Living organisms require a continual input of free energy for three major purposes:
– the performance of mechanical work in cellular movements,
– the active transport of molecules and ions across membranes,
– the synthesis of macromolecules and other biomolecules from simple precursors.
Roles of Metabolism
• to provide energy (catabolic processes)
• to synthesize molecules (anabolic processes)
• both types of processes are tightly connected
Two large groups of living organisms according to the chemical form of carbon they require from the environment:
1. Autotrophic cells ("self-feeding" cells): green leaf cells of plants and photosynthetic bacteria – utilize
CO2 from the atmosphere as the sole source of carbon for construction of all their carbon-containing
biomolecules.
2. Heterotrophic cells : cells of higher animals and most microorganisms – must obtain carbon in the form
of relatively complex organic molecules (nutrients such as glucose) formed by other cells.
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Unit 7 Forms of Energy
METABOLISM
Energy Is the capacity to cause change. Energy Exists in various forms, of which some can perform work
Kinetic energy is energy associated with motion
Heat (thermal energy) is kinetic energy associated with random movement of atoms or molecules
Potential energy : Is stored in the location of matter. It Includes chemical energy stored in molecular
structure
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Ml 105
Unit 7 The Laws of Energy Transformation
METABOLISM
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Unit 7 Equilibrium and Metabolism
METABOLISM
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A cell does three main kinds of work: Chemical, Transport and Mechanica
To do work, cells manage energy resources by energy coupling, the use of an exergonic process to drive
an endergonic one
Most energy coupling in cells is mediated by ATP
The Structure and Hydrolysis of ATP
ATP (adenosine triphosphate) is the cell’s energy shuttle
ATP is composed of ribose (a sugar), adenine (a nitrogenous base), and three phosphate groups
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Ml 105 ATP
Unit 7
How the Hydrolysis of ATP Performs Work
METABOLISM
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Unit 7
ATP
METABOLISM
How the Hydrolysis of ATP Performs Work
Another way that organisms extract energy from ATP is to “energize” organic compounds by transferring
a phosphoryl group directly to the compound.
In this reaction, ATP is dephosphorylated and an organic compound is phosphorylated, as shown in the
reaction below:
Chemical potential energy released by the conversion of ATP to ADP is transferred to the phosphorylated
organic product.
It is for this reason that we say “the organic compound is energized” in the reaction.
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Unit 7
COENZYMES in METABOLISM
METABOLISM
A reduction occurs when a hydride ion (H:¯) forms a bond with an organic compound.
The transfer of a hydride ion is a reduction because of hydride’s “extra” electron. For example, aldehydes
or ketones are reduced when a hydride ion forms a bond with them.
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Unit 7
COENZYMES in METABOLISM
METABOLISM
This is considered an oxidation because the hydride ion carries away the “extra” electron
Nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD) are classified as
coenzymes because they are common substrates, involved in the transfer of ________________, in
many different enzymatically catalyzed reactions.
These co-enzymes are very important for cell respiration because they transfer high-energy electrons to
electron transport systems (ETS).
As the electrons move from carrier to carrier, energy is released in small quantities.
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Unit 7
COENZYMES in METABOLISM
METABOLISM
When NAD+ accepts a hydride ion from another species, it is reduced to NADH.
It is for this reason that NADH is referred to as a reduced form of the coenzyme
The reduction of NAD+ requires energy.
When NADH donates a hydride ion (to another species) it is oxidized to NAD+
When NADH donates a hydride ion (to another species) it is oxidized to NAD+
Oxidation of NADH releases energy. 185
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Unit 7
COENZYMES in METABOLISM
METABOLISM
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Unit 7
COENZYMES in METABOLISM
METABOLISM
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Ml 105
Unit 7 Review Concept questions
METABOLISM
Ml 105
Unit 7
Metabolism
METABOLISM
The energy that is contained in food can be traced back to the SUN
Energy from sunlight is captured by plants during photosynthesis as they convert CO2 and H2O into
glucose and O2.
Without energy from sunlight, the reaction of CO2 with H2O to produce glucose and O2 is not
spontaneous.
The input of energy from sunlight provides the energy that is required to convert CO2 and H2O to glucose
and O2.
In photosynthesis, energy from the sun’s light does not vanish; it is converted to
_______________ _____________ _____________ within ________________.
Organisms, including humans, use a series of catabolic chemical reactions to slowly ______________
carbohydrates and other food, eventually converting it back to CO2 and H2O.
Energy that is released in these oxidations is converted to chemical potential energy within _______.
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Unit 7
Carbohydrate Metabolism
METABOLISM
Ml 105
Unit 7
METABOLISM
Overview of Catabolic Processes
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Ml 105
Unit 7 Stage 1: Digestion of Carbohydrates
METABOLISM
Digestion is the process in which the body breaks down carbohydrate, protein, and triglyceride polymers
into their smaller residues. For example, carbohydrate polymers are converted to monosaccharides.
Digestion occurs in the digestive system :
The digestive system, sometimes referred to as the digestive track or gastrointestinal (GI) track, includes
the organs that are responsible for digesting food and eliminating the undigestible components of food.
During the digestion of carbohydrate polymers
Carbohydrates Polymers are broken down to Disaccharides and monosaccharaides e.g Glucose etc.
Monosaccharides are transported into the cells by passive diffusion through transmembrane proteins
Using two main transporter: glucose transporter GLUT (1-14) and sodium-coupled glucose transporter
(SGLT )
NB:
The digestion of certain fats begins in the mouth, where short-chain lipids break down into diglycerides
and later in the small intestine into fatty acids.
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Food proteins are broken down into polypeptides and later into amino acids.
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Ml 105
Unit 7 Stage 2: Acetyl-Coenzyme A Production
METABOLISM
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Unit 7
METABOLISM
Stage 2: Acetyl-Coenzyme A Production
Step 01: Conversion of Glucose to Puruvate Notice that one glyceraldehyde 3-phosphate is produced in reaction 4 and a
second glyceraldehyde 3-phosphate is produced in reaction 5.
Therefore, each of the subsequent reactions in the pathway will occur twice
for each molecule of glucose that undergoes glycolysis.
Note that after reaction 5, glucose have been converted to two
glyceraldehyde 3-phosphate ions
Reaction 6) In this reaction, glyceraldehyde 3-phosphate is oxidized. An
oxidation cannot occur without a reduction.
In this case, NAD+ is reduced to NADH.
This occurs when a hydride ion (H:-) is transferred from glyceraldehyde 3-
phosphate’s carbonyl carbon to NAD+.
The reduction of NAD+ to NADH requires energy, that energy comes from
glyceraldehyde 3-phosphate.
The energy that is acquired by NADH can later be used to convert ADP to
ATP
The reactions of glycolysis result in a net gain of two ATP and two NADH.
REGULATION
When there is a sufficiently high concentration of ATP, pyruvate, or other
pathway products, then the rate of glycolysis can be slowed down.
If the ATP concentration becomes low, then glycolysis can be accelerated.
The rate of the glycolysis pathway is controlled by enzyme inhibitors and
enzyme activators of the enzymes involved in the irreversible reactions (1,
3, and 10).
For example, ATP and phosphoenol pyruvate (the product of reaction 9) act
as inhibitors of the phosphofructokinase enzyme that catalyzes reaction
194 3.
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Unit 7
METABOLISM
Stage 2: Acetyl-Coenzyme A Production
Step 01-b: Conversion of Non Glucose Monosacharides (Fructose, Galactose, mannose) to Puruvate
NB: enolase (inhibition by F-) : Whem blood samples are taken for mesurement of glucose, it is collected in
tubes containing fluoride
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Unit 7
METABOLISM
Stage 2: Acetyl-Coenzyme A Production
Step 02: Conversion of Pyruvate to Acetyl-CoA A.K.A The Fate of Pyruvate
The of Conversion of Pyruvate to Acetyl-CoA is called a transition reaction and is accomplished in two
ways;
1. In Aerobic Condition (Presence of O2) – Pyruvate is converted to Acetyl-CoA into the Krebs Cycle
2. In Anaerobic Conditions (Absence of O2) - Pyruvate is converted or Reduced to Lactate to replenish
NAD+ for glycolysis in presence of the enzyme lactate dehydrogenase.
Conversion or Reduction of Pyruvate takes place in the Mitochondria
Purpose? Pyruvate being converted to Acetyl Co-A and in turn Acetyl Co-A used to generate ATP, NADH,
FADH2, and CO2.
Ml 105
Unit 7 Stage 2: Acetyl-Coenzyme A Production
METABOLISM
In Anaerobic conditions, the pyruvate that is made in glycolysis remains in the cytoplasm and is
converted (reduced) to _______________, as shown in the reaction below.
Under aerobic conditions, pyruvate passes from the cytoplasm into the _____________________ and is
then converted to acetyl-coenzyme A and CO2 (as shown in the equation below).
Ml 105
Unit 7
Summary of Stage 2 of Carbohydrate Catabolism and the Fate of Pyruvate
METABOLISM
In Stage 2 of carbohydrate catabolism, under aerobic conditions, one glucose molecule has produced
two acetyl-coenzyme A ions, and provided the energy for the formation of four NADH and two ATP.
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Unit 7
METABOLISM
Energetic yield of glycolysis
1. Direct gain of ATP by substrate-level phosphorylation
This yield is the same for both, anaerobic and aerobic glycolysis. This is the only yield in anaerobic
glycolysis
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Unit 7
METABOLISM
ASSIGNMENT / LEARNING CHECK
Q.1 In tissues like the Lens and erythrocytes that lack mitochondria or function under limiting conditions of
oxygen, glycolysis is the predominant pathway providing ATP.
RBCs possess, in addition to glycolysis, a competing metabolic pathway that also utilizes glucose-6-phosphate:
the hexose monophosphate (HMP) shunt pathway (also known as pentose phosphate pathway.
The glycolytic pathway and the HMP pathway serve different functions in the RBCs.
1. What is the function of these two significant pathways to the red blood cell
2. How are these competing pathways regulated?
Q.2 Match the following with the terms : (1) Catabolic reactions (2) Coenzymes (3) Glycolysis (4) Lactate
A. Produced during anaerobic conditions (Ans:_______)
B. Reactions that convert glucose to pyruvate (Ans:_______)
C. Metabolic reactions that break down large molecules to smaller molecules + energy (Ans:_______)
D. Substances that remove or add H atoms in oxidation and reduction reactions (Ans:_______)
Q.3 List the enzymes involves in the conversion of Glucose to Pyruvate and state their functions
Q.4 During Laboratory glucose sample blood collection, a floride tube is preferably used. What is the purpose
of such tube. How does the tube achieve its intended purpose?
Q.5 How many ATP and NADH are produced when six glucose molecules undergo glycolysis respectiviely?
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Unit 7 Stage 3: The Citric Acid Cycle / TCA cycle (tricarboxylic
METABOLISM
acid cycle) or the Krebs cycle
The citric acid cycle is also known as the tricarboxylic acid cycle (TCA cycle) because of the three
carboxylic acid groups in citric acid, and the Krebs cycle after Hans A. Krebs, who deduced the reaction
sequence in 1937.
Purpose? Acetyl Co-A and in turn is used to generate ATP, NADH, FADH2, and CO2.
The citric acid cycle is characterized as a circular metabolic pathway while Glycolysis is linear
The citric acid cycle is the principal process for generating the reduced coenzymes NADH and FADH2,
which are necessary for the reduction of oxygen and ATP synthesis in the electron transport chain.
The citric acid cycle also functions as a source of intermediates for biosynthesis of other important
molecules (e.g., some amino acids).
The reactions of the citric acid cycle occur within the matrix of the mitochondria.
There are eight reactions in the cycle. Of particular importance are the reactions where NADH (Steps 3, 4,
and 8) and FADH2 (Step 6) are produced.
A two-carbon acetyl group enters the cycle (Step 1) and two carbon atoms are liberated as CO2 molecules
(Steps 3 and 4)
This series of reactions begins and ends with a C4 compound, oxaloacetate (hence the term cycle).
When one acetyl-CoA is completely processed in the citric acid cycle, three NADH, one FADH2, 201
one ATP, and two CO2 molecules are produced
Ml 105
Unit 7 Stage 3: The Citric Acid Cycle / TCA cycle (tricarboxylic
METABOLISM
acid cycle) or the Krebs cycle
In the first reaction, acetyl-coenzyme A (acetyl-CoA) reacts with oxaloacetate. In the citric acid cycle,
oxaloacetate is not only a reactant in the first reaction; it is also the product of the last reaction
In this process, energy that was originally contained in acetyl-CoA is converted to chemical potential
energy within NADH, FADH2 and ATP.
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Unit 7 Stage 3: The Citric Acid Cycle / TCA cycle (tricarboxylic
METABOLISM
acid cycle) or the Krebs cycle
NOTE: you do not need to memorize these reactions,
the names of the intermediates, or the names of the
enzymes that are involved
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Unit 7
METABOLISM
Stage 3: The Citric Acid Cycle - SUMMARY
The citric acid cycle is also known as the tricarboxylic acid cycle (TCA cycle) because of the three
carboxylic acid groups in citric acid, and the Krebs cycle after Hans A. Krebs, who deduced the reaction
sequence in 1937.
Purpose? Acetyl Co-A and in turn is used to generate ATP, NADH, FADH2, and CO2.
The overall chemical equation for the citric acid cycle metabolic pathway is:
acetyl-CoA + 3 NAD+ + FAD + ADP + Pi + 2 H2O ⇄ 2 CO2 + 3 NADH + FADH2 + ATP + H-CoA + 3 H+
Potential energy from an acetyl-CoA that undergoes the citric acid cycle is converted to potential energy
in three NADH, one FADH2, and one ATP. Some energy is lost as heat.
The CO2 produced in the citric acid cycle and in stage 2 of metabolism, is one of the end-products of food
metabolism.
CO2 is the most-oxidized form of carbon in organic compounds, and therefore has a very low energy
content.
Energy that was present in the food and food metabolites that contained these carbons has been
extracted in the catabolism process.
UNDERSTANDING CHECK:
Calculate the net gain of NADH, FADH2, and ATP from one glucose molecule that undergoes the first three
stages of catabolism.
***Keep in mind that glycolysis produces two pyruvate ions, which results in the production of two acetyl-CoA. 204
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Unit 7
Stage 4: Oxidative Phosphorylation /
METABOLISM
Electron transport Chain
The Electron Transport System ETS or Respiratory Chain) is the mechanism the cell uses to convert the
energy in NADH and FADH2 into ATP.
Electrons flow along an energy gradient via carriers in one direction from a higher reducing potential (greater
tendency to donate electrons) to a lower reducing potential (greater tendency to accept electrons).
The ultimate acceptor is molecular oxygen.
The ETC Is the assembly of respiratory enzymes or carrier proteins found in cristae or inner membrane of
mitochondria in eukaryotic cell and plasma membrane of prokaryotic cell
Occurs within all cells except RBCs and the cornea & lens of eyes
ETC Represents the final stage in the oxidation of carbohydrates, fats, and amino acids
ETC helps to Transfers reducing equivalents from NADH & FADH2 to O2
ETC Primes the process of ATP generation via oxidative phosphorylation
ETC Consists of four large protein complexes (I-IV)
Most active when there is an increased need for ATP
The different components of electron transport chain are NAD, FAD, Co-Q, Cyt-b, Cyt.-c1, Cyt.-c2 Cyt.-a, Cyt.-a3.
NAD and FAD are nucleotide and hydrogen acceptors. Co-Q is the complex organic compound and
hydrogen acceptors.
The term reducing equivalent is used to
Three types of electron transfers occur in oxidative phosphorylation: designate a single electron equivalent
transferred in an oxidation-reduction
– (1) direct transfer of electrons, as in the reduction of Fe3 to Fe2; reaction.
– (2) transfer as a hydrogen atom (H e); and
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– (3) transfer as a hydride ion (:H), which bears two electrons.
Ml 105
Unit 7
Stage 4: Oxidative Phosphorylation /
METABOLISM
Electron transport Chain
dfhhf
1. NADH transfers it’shydrogen's (each containing a
proton and an electron) to the electron carrier
protein
2. Some electron carrier proteins such as Coenzyme
Q can accept Protons as electrons are passed
through it
This increases the proton gradient across the
membrane and enhances the proton motive
force
3. During aerobic respiration, the last protein
transfers a pair of electrons to an oxygen
molecule to form H 20 (the O2 splits first)
4. The ATP synthase enzyme utilises the proton
motive force, and is able to use energy formed to
carry out the process of phosphorylation from
ADP to ATP
Ml 105
Unit 7
METABOLISM
Stage 4: Oxidative Phosphorylation
What is phosphorylation?
Formation of ATP from coupling of ADP and Pi is known as phosphorylation. Three types-
1. Substrate level phosphorylation
Enzymatic Transfer of phosphate from substrate to ADP to form ATP.
ATP made in glycolysis and the TCA cycle is the result of substrate- level phosphorylation
2. Photophosphorylation
Formation of ATP in light reaction of photosynthesis.
In which photosynthetic organisms capture the energy of sunlight—the ultimate source of
energy in the biosphere and harness it to make ATP
Photophosphorylation involves the oxidation of H2O to O2, with NADP as ultimate electron
acceptor; it is absolutely dependent on the energy of light.
3. Oxidative phosphorylation
Oxidative phosphorylation is the process in which ATP is formed as a result of the transfer of
electrons from NADH or FADH 2 to O 2 by a series of electron carriers. This process, which takes
place in mitochondria, is the major source of ATP in aerobic organisms
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METABOLISM
Stage 4: Oxidative Phosphorylation
How cells convert the stored metabolic energy of NADH and [FADH2] into ATP?......1
Ml 105
Unit 7
METABOLISM
Stage 4: Oxidative Phosphorylation
How cells convert the stored metabolic energy of NADH and [FADH2] into ATP? ……..2
In the course of electron transport, a proton gradient is established across the inner mitochondrial
membrane. It is the energy of this proton gradient that drives ATP synthesis.
In eukaryotes, oxidative phosphorylation occurs in inner mitochondrial membrane, and in prokaryote
occurs in plasma membrane.
Oxidative phosphorylation involves the reduction of O2 to H2O with electrons donated by NADH and
FADH2.
It occurs equally well in light or darkness.
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METABOLISM
Stage 4: Oxidative Phosphorylation
REVIEW QUESTION
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