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UNIT I:MOLECUELS TO ORGANISM:
STRUCTURES & PROCESSES
CHAPTER 4-FOOD & ENERGY
“ You cannot give what you do not have.” Druk Gyalpo
Aerobic respiration
Anaerobic respiration
Mechanism of respiration
Outline
Respiration
Types of respiration
Q and A
Design a solution to treat wastewater/ sewage/kitchen waste/municipal waste
using the idea of anaerobic respiration.
Objectives:
Develop a model that represents the events leading to the breakdown of food
during respiration (limited to basic concepts of glycolysis, Krebs cycle, and
electron transport chain).
Design a solution to enhance the flavor of food, based on the concept of cellular
respiration.
ENERGY SYSTEM
LESSON GOAL
• List 2 energy systems
• Give a basic description on how they work
• how aerobic respiration is more efficient than anaerobic respiration.
VIDEO) Cellular Respiration and the Mighty Mitochondria.mp4
INTRODUCTION
 Ultimte soource of energy - Sun
WHAT IS RESPIRATION?
It is a physic-chemical process that involves intake of oxygen by cells, oxidation
and breaking down of C-C bonds of respiratory substrates of food, mainly glucose
(but also sugars, organic acids, fats and proteins) with the release of CO2, H2O and
energy and storage of released energy in the form of ATP.
What is cellular respiration (biochemical process)?
The process of oxidative breakdown of food materials within the cell to
release energy trap it in the form of ATP is called cellular respiration.
ATP is energy currency of the cell
It consists of three components:
1. Adenine (nitrogenous base)
2. Ribose (5-carbon sugar or pentose sugar)
3. Phosphate (3 chains of phosphate groups)
ADENOSINE TRIPHOSPHATE
• Our body stores energy in the form of ATP
• ATP made up of 1 adenosine molecule and 3 phosphate molecules
Energy
• Our body requires energy, this energy comes from the
breakdown of ATP in our cells.
• All energy for cellular activity comes from ATP.
ATP Energy is released when the
phosphate bond is broken.
HOW ATP IS GENERATED?
• Our cells can’t get energy directly from food
• Needs to be stored as a useable form of energy ATP
• The food we eat contain energy (kilojoules)
• This energy is used to produce ATP molecules
• Energy is stored in ATP like a battery.
ATP IS LIKE A BATTERY FOR THE BODY
is broken down
to
Glucose
Fatty acids
Amino acids
Body uses ATP
when it needs to
Continuously recharging the
battery
ATP
Energy
released from
breakdown of
glucose is
stored in an
ATP Molecule
NUTRIENTS–RESPIRATORY SUBSTRATES
3 types of nutrients we can get energy from
• Carbohydrates
• Proteins
• Fats
• We digest these nutrients to convert them to other forms so we can used them to
generate ATP
• Carbohydrates glucose ATP
• Proteins amino acids ATP
• Fats fatty acids ATP
Respiratory substrate
Respiratory Substrate
Organic substance which are catabolised to release energy inside living cell
1.Carbohydrate
2.Fats
3.Protein
Floating respiration
Protoplasmic respiration
TRUE OR FALSE
• Glucose is the only useable form of energy our body can use.
False!
• ATP is the only useable form of energy
ATP is the energy currency of the cell. Justify
ENERGY SYSTEMS
• There are three energy systems responsible for manufacturing
ATP and there are two essential ways for ATP to be produced:
•The Aerobic Pathway
•The Anaerobic Pathways
AEROBIC ENERGY SYSTEM
• Continuous exercise lasting longer than 5 minutes like marathon, long
distance cycling.
Aerobic energy system-when is it used?
• Most efficient energy system- also slowest
• Can generate ATP in the presence of oxygen.
• Is used for long distance events or exercises lasting longer than 5
minutes.
• Based on oxidation of food in the presence or absence of oxygen (two types of cellular
reparation):
1. Aerobic cellular respiration
• Occurs in mitochondria of most cells (animals and plants) in presence of more oxygen.
• Organisms undergoing aerobic respiration are called aerobes
Two phases of aerobic respiration:
1. Glycolysis or anaerobic phase
• Take place in cytosol of the cell
• One glucose molecule is broken down into two molecules of pyruvic acid
2. Krebs cycle or aerobic phase
• Take place in mitochondria in presence of oxygen
• Pyruvic acids formed during glycolysis is completely broken down into carbon dioxide and water
Types of cellular Respiration
Aerobic cellular respiration
Catabolic process
Complete oxidation (water and carbon dioxide are end product)
 common substrate = Glucose
Glucose is derived from starch (hydrolysis) and sucrose by enzymic action.
40% of the energy in glucose is used to make ATP (aerobic is efficient)
Any energy not used to produced ATP is lost as heat.
Starch + maltose Glucose
Sucrose + Glucose + Glucose
H2O
H2O
Amylase Maltase
Invertase
WHY?
38 ATP MOLECULES IN AEROBIC RESPIRATION
• Complete breakdown of food due to
presence of oxygen
• There is final hydrogen acceptor due to
production of water, therefore, the ETC
take place.
• Hence, produce 38 ATP molecules from
one glucose molecule
2. Anaerobic cellular respiration
• Occurs in cytosol of the cell in absence of oxygen
• Incomplete oxidation of food
• Occurs in lower organisms (yeast, certain bacteria and fungi), hence called anaerobes.
• Occurs in higher animals and plants (when oxygen is limited)
• Produce only 2ATP molecules or 59 kcal from one glucose molecule.
Two types of cellular respiration cont.
Beaking down of Pyruvic acid
1. In yeast, bacteria and some plants
Pyruvic acid (C3H4O3) Enzymes Ethyl alcohol + Carbon dioxide (Alcoholic fermentation)
2. In anaerobic animals
Pyruvic acid (C3H4O3) Enzymes Lactic acid (Lactic acid fermentaion)
WHY?
ONLY 2 ATP MOLECULES IN ANAEROBIC RESPIRATION
• Incomplete breakdown of food as
no oxygen
• No final hydrogen acceptor
because water is not produce),
therefore, the ETC cannot take
place
• Hence, produce only 2 ATP
molecules from one glucose
molecule
• Glucose is converted to 2 molecules of
pyruvate in glycolysis
• NAD is reduced to NADH
• There is a net production of 2 ATP
THERE ARE TWO ALTERNATE PATHWAYS
1. Ethanol pathway
2. Lactate pathway
Ethanol pathways/alcoholic fermentation
• This occurs in some plants and yeast
• It takes place in the cytoplasm.
ETHANOL PATHWAYS/ALCOHOLIC FERMENTATION
• Glycolysis occurs in the
cytoplasm
• ATP is being made, even though
it is in a small amount
• NAD is reduced
• Pyruvate is decarboxylated to
ethanal
• The CO2 given off here is what
makes bread rise when dough is
mixed with yeast.
ETHANOL PATHWAYS/ALCOHOLIC FERMENTATION
• Ethanal is reduced to ethanol using
hydrogen from NADH. The enzyme required
for this process is called dehydrogenase.
THE LACTATE PATHWAY
• This occurs in mammalian skeletal muscle
during exertion
• When pyruvate from glycolysis is produced
faster than it can be oxidized in the Krebs cycle.
• This is because the supply of oxygen cannot
meet the demand.
• Pyruvate acts as the hydrogen acceptor. It
accepts hydrogen from NADH.
• NADH can go back to NAD+ and keep
glycolysis going.
• Pyruvate is converted to lactate by lactate
dehydrogenase.
THE LACTATE PATHWAY
• ATP is made in small amounts by glycolysis
• The skeletal muscles can continue to work.
• Lactate is toxic and must be removed. This pathway can be reversed but needs
oxygen.
• An oxygen debt therefore exists.
• Lactate is carried in the blood from the muscles to the liver.
• 20% is oxidized to CO2 and H2O
• 80% is converted to glycogen and stored.
LACTIC ACID ENERGY SYSTEM
• Also known as the anaerobic energy system
• Breaks down glucose and glycogen to form ATP
• Generating ATP through this energy system also produces lactic acid
• Lactic acid causes our body to fatigue.
• Therefore can only be used for exercise lasting 2-3 minutes
• Lactic build up makes muscles feel heavy and tired.
When is it predominantly used?
• Intense exercise lasting 2-3 minutes
• 400-800m run
• Many team sports- netball, football, etc.
METABOLIC PATHWAY
1. Carbohydrate metabolic pathway
2. Protein metabolic pathway
3. Lipid metabolic pathway
• All the metabolism are taking place in cellular respiration.
Why cellular respiration?
• The idea of cellular reparation is to use all macromolecules to generate
energy.
• All the macromolecules (carbohydrates, proteins and fats) contain energy
that was made by plants undergoing photosynthesis.
CARBOHYDRATE METABOLIC PATHWAY
1. Glycolysis
• Convert glucose into pyruvate or pyruvic acid
2. Pyruvate Dehydrogenase complex
• Decarboxylation—conversion of Pyruvic acid into Acetyl CoA in mitochondrial matrix.
• What is decarboxylation?
• The removal or release of one CO2 molecule from the pyruvate (meaning one carbon is released
to form acetyl CoA.
• Why carboxylation is important?
• Because pyruvate cannot enter into Krebs cycle, only acetyl CoA molecule get inside the Krebs
cycle.
• Only Acetyl CoA and Krebs cycle let cell to undergo aerobic respiration.
3. Krebs cycle
• Acetyl CoA oxidized (O2) into ATP, NADH and FADH2
4. Electron transport system
• Electron carriers (NADH and FADH2) produce more ATP
Major steps involved in aerobic respiration
1. Glycolysis
2. Oxidation of pyruvate to acetyl CoA
3. Krebs cycle
4. Electron transport chain
5. Oxidative phosphorylation
1. GLYCOLYSIS OR EMP PATHWAY (EMBDEN'S MEYERHOF
AND PARNAS PATHWAY)
Where? • The cytosol
What? • Breaks down glucose to pyruvic acid or
pyruvate.
• Glycolysis is called
common pathway for
both cellular respiration
10 successive reactions
@Sherab Tenzin/OCS-2022
GLYCOLYSIS
• During this process one molecule of glucose (6
carbon molecules) is degraded into two
molecules of pyruvate (3 carbon molecules).
• Free energy released in this process is stored
as 2 molecules of ATP and 2 molecules of
NADH.
1. Glycolysis or EMP pathway (Embdens Meyerhof and Parnas Pathway)
 By German scientists—Embden's, Meyerhof and Parna in 1930s.
 Glycolysis is called the common pathway because initial steps of glycolysis are common to
both aerobic and anaerobic respiration.
Steps for glycolysis:
A. Energy spending phase (Preparatory phase)/Priming
Three reactions occur in the conversion of glucose to fructose 1, 6-biphosphate.
1. Phosphorylation of glucose (First phosphorylation)
Steps for glycolysis:
2. Formation of fructose 6-phosphate
3. Formation of fructose 1, 6-biphosphate (second phosphorylation)
B. Splitting phase (Splitting and rearrangement phase)
4. Lysis or splitting
• Fructose 1, 6-biphosphate splits up to form one molecule of each 3-carbon compounds Glyceraldehyde 3-
phosphatte (3-phosphoglyceraldehyde=PGAL) and dihydroxy acetone 3-phosphate (DiHAP).
Glycolysis or EMP pathway (Embdens Meyerhof and Parnas Pathway)
Glycolysis or EMP pathway
Steps for glycolysis:
5. Isomerization of DiHAP
C. Energy Conserving Phase (Pay off phase/Energy Extraction)
6. Oxidation and phosphorylation
• PGAL is oxidized by the action of enzyme glyceraldehyde phosphate dehydrogenase
(phosphoglyceraldehyde dehydrogenase) by removing of hydrogen and addition of phosphate to
form 1, 3-biphosphoglyceric acid.
• NAD+ is hydrogen acceptor. It picks up hydrogen from glyceraldehyde 3-phosphate and produces
NADH + H+
Steps for glycolysis:
7. Substrate level phosphorylation (formation of ATP)
1, 3-biphosphoglyceric acid transfers one phosphate group to ADP and changes to 3-phosphoglycerate
in presence of enzyme phosphoglycerate kinase.
8. Isomerization or rearrangement
• 3-phosphoglycerate is changed to its isomer 2-phosphoglycerate in presence of enzyme
phosphoglyceromutase
9. Dehydration
• 2-phosphoglycerate loses water in presence of enzyme enolase and changes into phosphoenol pyruvate. It
undergoes molecular rearrangement and its-PO4 group is changed to high energy phosphate bond.
Glycolysis or EMP pathway
Glycolysis or EMP pathway
@Sherab Tenzin/OCS-
2022
Steps for glycolysis:
10. Formation of pyruvate and substrate level ATP synthesis
• High energy phosphate group of phosphoenol pyruvate is transferred to
ADP with help of enzyme pyruvate kinase. This produces pyruvic acid or
pyruvate and a molecule of ATP.
Glucose (6C)
Glucose 6-phosphate (6C)
Fructose 6-phosphate (6C)
Fructose 1, 6-Biphosphate (6C)
Glyceraldehyde- 3-phosphate (3C)
1, 3 Biphosphogylceric acid (3C)
3- Phosphogylceric acid (3C)
2- pyruvic acid
Phosphoenol pyruvate
Dihydroxy Acetone
Phosohate (3C)
ATP
ADP
Hexokinase, Mg2+
phosphohexoisomerase, Mg2+
ATP
ADP
phosphofructokinase, Mg2+
NAD+
NADH + H+
Aldolase
Glyceraldehyde phosohate dehydrogenase
Phosphoglycerate kinase, Mg2+
ADP
ATP
phosphoglyceromutase
2- Phosphogylceric acid (3C)
Enolase
H2O
Pyruvate kinase, Mg2+, K+
ADP
ATP
Glycolysis or EMP
Energy
spending
phase
Pay off phase/Energy exraction
Net product of glycolysis
Glucose Glucose 6- phosphate (1ATP is used)—Step 1
Fructose 6-phosphate Fructose 1, 6-biphosphate(1ATP is used)—step 3
1, 3-Biphosphoglyceric acid 3-phosphoglyceric acid (2 ATP is produced)-step 7
2- Phosphoenol pyruvic acid pyruvate (2ATP is produced)—Step 10
Net gain is = 4 - 2 = 2ATP
2. Each NADH produces 3 ATP: 2NAD + 2H+ +4e
1.
2NADPH
2NADPH 2x3=6ATP
So net gain in glyvolyis is 6ATP + 2 ATP= 8ATP
How many ATP is produced at the end of Glycolysis?
• This process reduces the co-factor NAD+ to NADH.
• This is important, as later in the process of cellular respiration, NADH will
power the formation of much more ATP through the mitochondria’s
electron transport chain.
2. Oxidation or oxidative decarboxylation of pyruvate to acetyl CoA
• Pyruvate generated in glycolysis gets into the mitochondria through specific transport protein Coenzyme A.
• Pyruvate undergo oxidative decarboxylation
• Reaction is catalyzed by pyruvate dehydrogenase and several coenzymes like, NAD+, coenzyme A (CoA),
thiamine pyrophosphate (TPP), lipoic acid, transacetylase and Mg2+ etc.
• Glycolysis link with Krebs cycle, hence it is called link/transitional reaction or gateway step.
-Glycolysis -Krebs cycle
(Waste)
Oxidation
(to ETC)
(use in Krebs cycle)
• Pyruvate is oxidized in to acetate
• NAD+ is reduced into NADH
2. OXIDATION or OXIDATIVE DECARBOXYLATION OF
PYRUVATE TO ACETYL CoA
• Oxidative decarboxylation, sometimes referred to as the link reaction or the
transition reaction, is the link between glycolysis and the citric acid cycle.
• Pyruvate is transferred into the mitochondrial matrix via a protein known as pyruvate
translocase. Here, the pyruvate is combined with Coenzyme A to release a carbon
dioxide molecule and form acetyl-CoA. Hence, called decarboxylation.
• This transition reaction is important because acetyl-CoA is an ideal fuel for the
citric acid cycle, which can in turn power the process of oxidative phosphorylation in
the mitochondria, which produces huge amounts of ATP.
• More NADH is also created in this reaction. This means more fuel to create more ATP
later in the process of cellular respiration.
Digestive Glands
3. Krebs cycle or Tricarboxylic Acid (TCA) Cycle
• Where?
• What?
• In the mitochondria
• Uses Acetyl CoA to generate ATP, NADH, FADH2 and
CO2.
KREBS CYCLE OVERVIEW
• The Krebs cycle is contained within mitochondria. Within the mitochondrial matrix, the
reactions of the Krebs cycle adds electrons and protons to a number of electron carriers,
which are then used by the electron transport chain to produce ATP.
• The Krebs cycle starts with the products of glycolysis, which are two three-carbon molecules
known as pyruvate.
• This molecule is acidic, which is why the Krebs cycle is also called the tricarboxylic acid
cycle (TCA). Throughout a number of reactions, these molecules are further broken down into
carbon dioxide.
• Energy from the molecules is moved to other molecules, called electron carriers. These
molecules carry the stored energy to the electron transport chain, which in turn creates ATP.
• Altogether, the Krab's cycle consists of 9 sequential reactions.
KREBS CYCLE PRODUCTS
• Acetyl CoA is utilized within the Krebs cycle to produce several major
products. In turn, these products then drive the formation of ATP, the
cell’s main energy source.
• Before the first stages of the Krebs cycle, pyruvate is converted into
acetyl CoA. During this process, one molecule of CO2 and one molecule
of the electron carrier NADH are produced.
• The Krebs cycle involves converting this acetyl CoA into carbon dioxide.
• During the steps of the cycle, two molecules of CO2 are released, in
addition to 3 more molecules of NADH, one of FADH2, and one of GTP.
SO, FOR EVERY 1 PYRUVATE MOLECULE ADDED, THE
KREBS CYCLE WILL PRODUCE:
• 2 molecules of CO2
• 3 molecules of NADH
• 1 molecule of FADH2
• 1 molecule of GTP
• A molecule of glucose contains 2 pyruvate molecules, so 1 glucose molecule will
produce double the amount of products listed above as it moves through the Krebs
cycle. These products will then be converted to ATP in later stages of aerobic
respiration. Carbon dioxide is the only “waste” product and must be removed
from the cell.
3. Krebs cycle or Tricarboxylic acid (TCA) cycle
• Steps were studied by English biochemist Hans A. Krebs
• Cycle is also known as citric acid cycle as the initial product formed is citric acid (C6H8O7).
It has following steps:
(1) Condensation or formation of citrate(6-carbon compound)
• Acetyl CoA reacts with Oxaloacetate (C4H4O5) forming a 6-carbon compound called citrate in presence of
condensing enzyme called citrate synthetase.
(2) Isomerization (formation of isocitrate)
• Citrate undergoes reorganization forming a 6-carbon compound called cis-aconitate in presence of enzyme called aconitase.
Water also release here.
• Cis-aconitate further reorganized into 6-carbon isocitrate in presence of enzyme aconitase, with addition of water.
3. Krebs cycle or Tricarboxylic acid (TCA) cycle
• It has following steps cont.:
(3) Second oxidative decarboxylation (Formation of α-ketoglutarate) 5-carbon compound:
• Isocitrate undergoes oxidative decarboxylation forming oxalosuccinate in presence of enzyme called isocitrate
dehydrogenase and Mn2+. Oxalosuccinate undergoes decarboxylation forming 5-compound called α-
ketoglutarate.
(4) Third oxidative decarboxylation of α-ketoglutarate
• α-ketoglutarate undergoes dehydrogenation and decarboxylation together in the presence of enzyme called α-
ketoglutarate dehydrogenase complex.
• This complex contains TTP, lipoic acid, Mg2+ and transsuccinylase. Here, NAD+ and CoA also required.
3. Krebs cycle or Tricarboxylic acid (TCA) cycle
@Sherab Tenzin/OCS-
2022
• It has following steps cont.:
(5) Synthesis of ATP/GTP
• Succinyl CoA undergoes reaction in presence of enzyme succinate or succinyl CoA synthetase thiokinase
forming 4-carbon compound called succinate.
• In this reaction it releases energy to form ATP or GTP.
(6) Dehydrogenation oxidation of succinate:
• The succinate is dehydrogenated to a 4-carbon compound called fumarate in presence of enzyme succinate
dehydrogenase and 2-hydrogen atoms are released.
• Hydrogen atoms are received by FAD (Flavin adenine dinucleotide) and reduced to FADH2.
3. Krebs cycle or Tricarboxylic acid (TCA) cycle
@Sherab Tenzin/OCS-
2022
It has following steps cont.:
(7) Hydration of fumarate:
• Here, fumarate changes to a 4-carbon compound called malate in presence of enzyme fumarase and water.
(8) Oxidation of malate or Dehydrogenation:
• Malate is oxidized or dehydrogenated to oxaloacetate in presence of NAD+ and enzyme malate
dehydrogenase. In this reaction, 2 hydrogen atoms are released to form NADH+H+
Krebs or Tricarboxylic acid
(TCA) cycle
Steps of TCA
tOxalosuccinate
3. 2nd oxidative
Decarboxylation
1. Condensation/formation
of citrate
2. Isomerisation
4. 3rd oxidative
decarboxylation
5. Synthesis of
ATP/GTP
6. Dehydrogenation
oxidation of succinate
7. Hydration of
fumarate
8. oxidation of malate
III. Summary of krebs cycle or TCA
cycle
1
2
3
4
1. Introduction of CoA initiates TCA
2. 3 molecules of water used and
released one
3. Complete oxidation of CoA
released 2 molecules of CO2
4. Four oxidation (4 H+) 3NAD+ H+
=3NADH + H+
FAD + H+ = FADH2
5. One molecules of GTP is released
6. Oxaloacetate is regenerated
Mnemonic—intermediate and enzymes
Cook—citrate synthetase
Again—Aconitase
In—Isocitrate dehydrogenase
Another—alpha-ketoglutarate
dehydrogenase
Super—Succinyl CoA synthetase
Stove—succinate dehydrogenase
For—Fumarase
Me—malate dehydrogenase
Can—citrate or citric acid
I—isocitrate
Keep—Ketoglutarate
Some—succinyl CoA
Sugar—Succinate
For—Fumarate
Myself—Malate
Only—Oxaloacetate
iii. Significance of krebs cycle
1. TCA is the major pathway for
releasing the energy (out of 36/38, 30
ATP is released by TCA)
2. Provides common pathway for
oxidation of carbohydrates, fatty acid
and amino acid
3. Intermediate products of TCA provide
raw materials for anabolic pathways:
i. Acetyl CoA = fatty acid, gibberellins
etc,.
ii. A-ketoglutaric acid = glutamic acid
iii. Succinyl CoA = cytochrome,
phytochrome and pyrrole ring of
chlorophyll
iv. Oxaloacetic acid = amino acid asparate
SIGNIFICANCE OF KREBS CYCLE
• Without Krebs cycle—not generate electron donors such as FADH2 & NADH.
• In Krebs cycle no generation of any single ATP molecule, therefore, the primary
function is to provide ATP energy.
• It is the common pathway for the oxidation of carbohydrate, lipids and protein via
acetyl CoA or intermediate of the cycle.
• Citric acid cycle is an amphibolic process i.e. it plays role in both oxidative
(catabolic) and synthetic (anabolic) processes.
• E.g.: catabolism occurs when the citric acid cycle oxidizes the two carbon atoms
of acetyl CoA to carbon dioxide (CO2).
• Anabolism occurs when the citric acid cycle generates reduced factors such as
NADH and FADH2.
 Occurs at the end of the metabolic reaction of aerobic respiration.
 It involves direct reaction between oxygen and hydrogen producing water.
Terminal oxidation is the final steps of aerobic respiration and involves two major stteps:
1.Transport of electron
2.Oxidative phosphorylation
NADH + H+ NAD + 2H+ + 2e-
FADH2 FAD + 2H+ + 2e-
𝟏
𝟐
O2 + 2H+ 2e- H2O
Terminal Oxidation
ELECTRON TRANSPORT/RESPIRATORY CHAIN
What?
• It is the transfer of electrons from NADH and FADH2 to oxygen via multiple protein
carriers.
• Location of ETC—it is embedded in the mitochondrial membrane.
• In the ETS—it consists of series of electron carrying molecules (5 enzyme
complexes)
1. Complex I—NADH dehydrogenase/ubiquinone oxidoreductase
2. Complex II—succinate dehydrogenase/ubiquinone oxidoreductase
3. Complex III—ubiquinone cytochrome C oxidoreductase
4. Complex IV—cytochrome C oxidase
5. Complex V—ATP synthase—for oxidative phosphorylation (complex V is not participate in
electrons transportation)—it is to synthesize ATP molecules
Take part in ETC
ELECTRON TRANSPORT/RESPIRATORY CHAIN
• All the 5 enzyme complexes are part of inner mitochondrial membrane.
• Only 4 protein complexes I, II, III and IV take part in electron transportation from one
complex to another complex but complex IV take part in synthesizes of ATP molecules
by under going oxidative phosphorylation.
• The polypeptides of complexes originate from the 13 proteins encoded by
mitochondrial DNA and from nuclear encoded proteins.
• Other functions of mitochondria:
• Apoptosis
• Production of reactive O2 species
• Calcium homeostasis
• Immunity process
ROLE OF ETS/RC
• Carbohydrate into pyruvate + 2ATP + NADH—Glycolysis (anaerobic respiration).
• Pyruvate into Acetyl CoA—Decarboxylation (PDH complex).
• Acetyl CoA into energy rich compound such as NADH and FADH2)
• Since, there is no ATP production in Krebs Cycle (TCA cycle), hence, ETC is very
important to convert energy rich compound produced in glycolysis and Krebs cycle (NADH
& FADH2) in to ATP molecules.
• The electrons derived from NADH and FADH2 will transfer to carrier protein
complexes and finally to O2 molecules inside the mitochondrial matrix. As a result,
ATP molecules synthesis from ADP by undergoing an oxidation/reduction
reaction (redox reaction).
• ATP is used by the cell as the energy for metabolic processes for cellular functions.
WHY ETC?
• 70% of Oxygen consumed by body cells is used by ETC to produce ATP.
• Finally, electrons donated by NADH and FADH2 are accepted by oxygen to
generate currency energy called ATP (Adenosine triphosphate).
IMPORTANCE OF ECT
• Without Krebs cycle, not generate electron donors (FADH2 & NADH).
• In Krebs cycle, no generation of any single ATP molecule. Only one molecule of GTP is
produced.
• In Krebs cycle only produce more and more NADH and FADH2 molecules.
• Whereby, NADH and FADH2 are further energize to produce more ATP molecules.
• 1 molecule of NADH produces 2.5 ATP molecules.
• 1 molecule of FADH2 produces 1.5 ATP molecules. Hence, ECT is very important.
WHERE DOES THE ETC OCCUR?
• ETC and ATP synthesizing system are located on inner mitochondrial membrane.
• Inner mitochondrial membrane is rich in proteins.
Component of ETC:
1. Electron acceptor—NADH and FADH2
2. Complexes
3. Mobile electron carrier
i. FMN
ii. Co-Enzyme Q or ubiquinone
iii. Iron-sulfer protein (Fe-S)—associated with FMN & Cytochrome b
iv. Cytochromes (heme proteins)
a. b
b. c1
c. c
d. a
e. a3
TYPES OF CYTOCHROMES
• Only cytochrome c is water soluble and diffuses easily. Therefore, it plays an important
role in programmed cell death (apoptosis—programmed cell death).
• Cytochrome b, cytochrome c1 and cytochrome a and a3 are lipid soluble, therefore they
are fixed components of inner mitochondrial membrane and they are part of electron
complexes.
• Cytochrome a and a3 together also called cytochrome oxidase (they also contain
copper).
• Co-Q and cytochrome c—are not the part of the inner mitochondrial membrane.
Therefore, not the part of complexes. Located outside the inner MM. They just act as
electron acceptor or electron carrier.
• Complex I, II, III and IV—are part of inner MM. They are arranged in order of increasing
WHAT IS INCREASING REDOX POTENTIAL?
• When electrons flow from a negative redox reaction to a positive redox reaction.
• Electrons always travel from reactants with negative redox potential (electronegative) to
positive redox potential (electropositive). Therefore, complex I has –ve redox potential
and complex IV has more +ve redox potential.
• Due to redox potential difference between complexes, electrons always flow from
complex I to complex IV.
• Redox potential is main factor for the transportation of electrons because the reactant
with –ve redox potential is the best donor and reactant with +ve redox potential is the
best acceptor.
• Low redox potential (-ve)—electron donor
• Hight redox potential (+ve)—electron acceptor
PROCESS OF ELECTRON TRANSPORT SYSTEM
A. Electron acceptors—hydrogen ions and electrons produced in mitochondrial matrix
are picked up by two hydrogen acceptors coenzymes.
i. NADH—nicotinamide adenine dinucleotide—NADH pathway
ii. FADH2-Flavin adenine dinucleotide—FADH2 pathway
By picking up hydrogen ions NAD and FAD are reduced to NADH+H+ and FADH2
B. Complexes
1. Complex I—it is also called NADH dehydrogenase-ubiquinone oxidoreductase
• NADH produced from PDH complex and TCA cycle transfer electrons to complex I.
• NADH enter the complex I and receives electrons from NADH.
• In complex I present FMN, which receives e- and transfer e- to Fe-S protein.
• From Fe-S e- are transferred to Co-Q. Once electrons are transferred to Co-Q, during this
stage, 4H+ are pumped into intermembrane space of mitochondria.
PROCESS OF ELECTRON TRANSPORT SYSTEM
B. Complexes
2. Complex II—it is also called succinate dehydrogenase-ubiquinone
oxidoreductase (key enzyme of TCA cycle—only enzyme located in inner
mitochondrial membrane)
• In complex II, electrons are transfer for FADH2 to complex II and to Co-Q, and
then to complex III.
• But in FADH2 pathway (route II) no protons (hydrogens ions) are pump into
intermembrane space.
3. Complex III—it is also called as ubiquinone cytochrome c oxidoreductase
• Complex III contains cytochrome b, c1 and Fe-S.
• Here electrons are transfer from cytochrome b to Fe-S and to cytochrome C1.
• At this point, again 4H+ (protons) are pumped into intermembrane space.
PROCESS OF ELECTRON TRANSPORT SYSTEM
B. Complexes
4. Complex IV—it is also called as cytochrome c oxidase.
Why it is called as oxidase?
• Because it uses molecular oxygen to accept electrons which are donated by
cytochrome c.
• Cytochrome C transfer electrons to complex IV.
• In complex IV—it contains cytochrome a and cytochrome a3 (it also called
Heme aa3 and copper A & copper B centre).
• Oxygen is the final electron acceptor in ETC.
• Electrons are transfer from cytochrome C to cytochrome a, then to cytochrome
a3, finally to oxygen molecules.
• When electrons are accepted by oxygen, it forms water.
• In complex IV—2 protons are pumped into intermembrane.
@Sherab Tenzin/OCS-
2022
TWO ROUTE/PATHWAY OF ETS
1. Route I—it also called NADH pathway
• Here, electrons are transfer from NADH to complex I
• Total of 8 electrons are pumped through NADH pathway into
intermembrane space.
2. Route II—it also called FADH2 pathway
• Here, electrons are transfer from FADH2 to complex II
• Total of only 4 protons are pampered through FADH2 pathway into
intermembrane space.
NUMBER OF PROTONS IN INTERMEMBRANE SPACE
If ETC starts with NADH—10 protons
If ETC starts with FADH2—6 protons
Therefore, NADH pathway (route I) is better than FADH2 (route 2), because
there is difference in production of ATP in the body.
COMPLEX V—ATP SYNTHASE
• It is component of oxidative phosphorylation.
• It is the smallest molecular motor in the body.
• Due to pumping of protons into the intermembrane space, it creates electro-
chemical proton gradient across the inner mitochondrial membrane.
• There is high proton gradient in intermembrane space and low proton gradient
in the matrix. Therefore, protons flow from high gradient to low gradient through
complex V (F1 to F0) and produce ATP molecules.
• Where ADP + iP—ATP in F1 subunit.
• Every 4H+ protons = 1 ATP molecules.
NUMBER OF ATP GENERATE IN MITOCHONDRIA
NADH pathway—10 protons =4+4+2
=1+1+0.5=2.5 ATP molecules
FADH2 pathway—6 protons =4+2
=1+0.5=1.5 ATP molecules
Therefore, NADH pathway produced more ATP molecules than FADH2
pathway.
Substrat
e
FA
D
FMN
Co-Q
e- from FADH2
e- from NADH+ + H
Complex II-Route-
2
Complex I-Route-1
No H+ (proton)
4H+ (proton)
Complex III—Cytochrome b. c1
Cytochrome c
Complex IV—Cytochrome a. a3
O2 + 2H+ = H2O
4H+ (proton) 4H+ (proton)
2H+ (proton)
2H+ (proton)
2e-
2e-
2e-
2e-
2e-
2e-
Route
of
ETC
• Electrons enter the ETC through two routes:
1. FMN (complex I)—route 1
2. FAD (complex II)—route 2
• Both routes converge at coenzyme Q (accept electrons).
Events:
1. NADH + H + formed in pyruvic acid oxidation and in Krebs cycle transfers its electrons and H + ions to FMN
(first electron carrier in route 1 of ETC).
In this transfer,
• NADH is oxidized
• FMN is reduced to FMNH2 .
• NAD is again used in the reaction of pyruvic oxidation and TCA cycle.
2. Electrons from succinic acid in Krebs cycle are picked by FAD (first electron carrier in route 2 of ETC).
• The reduced coenzyme Q (ubiquinone) is then oxidized by transfer of electrons to cytochrome c via
cytochrome b-c complex (complex III).
• The reduced cytochrome c (the mobile carrier) then transfer electrons to complex IV (the cytochrome c
oxidase complex).
Mechanism of transport of electrons and protons and redox
potential
Mechanism
Cyt.b-(FeS)-Cyt.c1
Cytochrome c
Cyt.a
Cyt.a3
Oxygen
• The electron transferring reactions are called oxidation-
reduction reaction or redox reaction.
• The electron donor and electron acceptor form redox pair.
• Electron flow from the high electronegative components to
the high electropositive components.
• A compound which is a reducing agent in one reaction
becomes an oxidizing agent in another.
What is redox reaction?
• Peter Mitchell proposed chemiosmotic theory to explain the OP.
• The Synthesis of ATP from ADP and inorganic phosphate (iP) in F0 – F1 particles of
ATP synthetase in mitochondria is called oxidative phosphorylation.
 Transport of electrons from one molecule of NADH + H+ over ETC helps in the transport
of 10 protons from intermembrane space to mitochondrial matrix and this generates 2.5/3
ATP molecules.
 Transport of electrons from one molecule of FADH2 helps in the transport of 6 protons
and generates 1.5/2 ATP molecules.
ATP synthetase consists of two major components:
1. F0 or Base piece
2. F1 or Head piece
What is Oxidative phosphorylation?
Elementary particles
or Oxysomes or Fo – F1
or Rackers particles
embedded in inner
Mitochindrial membrane.
1. Head
2. Base
3. Stalk
Each oxysomes is differentiated into:
Function as enzymes: ATPase
ATP=ADP
 Center for ATP synthesis during
oxidative phosphorylation
 Base piece has roter and stator
 Has channel between called proton tunnel
 Embedded in lipid bilayer
ATP Synthesis
• F0 piece provides channel for proton to cross inner membrane and reach
to F1 piece.
• F1 piece is site for ATP synthesis
• ATP synthesis depends on the proton gradient in the F0– F1 particle,
higher at F0 and lower at F1
• Proton gradient activates ATP synthetase in the F1 particle
• Passage of a pair of proton in F0 – F1 particle produce one ATP molecule.
• This hypothesis of ATP synthesis is called Chemiosmotic coupling
hypothesis
ATP Synthesis
CHEMIOSMOTIC THEORY
• The transport of electrons from inside to outside of IMM is accompanied by the
generation of a proton gradient across the membrane.
• Protons (H+) accumulate outside the membrane creating an electrochemical potentia
difference.
• The protons pumps (complexes I, III, IV) expels H+ from inside to outside of the
membrane.
• So there is high H+ concentration outside. This causes H+ to enter into mitochondria
through the channels (F0-F1 complex), this proton influx binds to oxygen of Pi + ADP
to form ATP.
@Sherab Tenzin/OCS-
2022
CURRENT CONCEPT OF ATP SYNTHESIS
• Proton gradient is created across the IMM till the electrons are
transferred to oxygen to form water.
• This electrochemical potential of this gradient is used to
synthesize ATP.
RECENT CONCEPT OF: SITES OF ATP SYNTHESIS
• Traditionally between complex I and coenzyme Q- First site
• Between complex III and cytochrome C-second site
• At complex IV and Oxygen-third site
• Now the ATP synthesis occurs when proton gradient is
dissipated and not when protons are pumped out.
Homework
1. Which type of respiration is more efficient and why?
2. Why would glycolysis be considered an inefficient energy process?
3. Why is it important to breakdown the pyruvate?
4. What is the role of oxygen in aerobic respiration?
5. Suppose that each fatty acid in a certain fat can make 9 molecules of acetyl CoA.
Predict how many ATP can be made from the fatty acids in this fat. (Remember there
are 3 fatty acids in the fat molecule.)
6. NADH pathway is better than FADH2 pathway. Justify.
7. ECT is more important than Krebs cycle. Why?
8. What makes electrons to flow from one complex to another?
Any muddiest point my dear students
Thank you for your attention!

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ppt chapter 4 respiration- The source of energy.pptx

  • 1. UNIT I:MOLECUELS TO ORGANISM: STRUCTURES & PROCESSES CHAPTER 4-FOOD & ENERGY “ You cannot give what you do not have.” Druk Gyalpo
  • 2. Aerobic respiration Anaerobic respiration Mechanism of respiration Outline Respiration Types of respiration Q and A
  • 3. Design a solution to treat wastewater/ sewage/kitchen waste/municipal waste using the idea of anaerobic respiration. Objectives: Develop a model that represents the events leading to the breakdown of food during respiration (limited to basic concepts of glycolysis, Krebs cycle, and electron transport chain). Design a solution to enhance the flavor of food, based on the concept of cellular respiration.
  • 5. LESSON GOAL • List 2 energy systems • Give a basic description on how they work • how aerobic respiration is more efficient than anaerobic respiration. VIDEO) Cellular Respiration and the Mighty Mitochondria.mp4
  • 7. WHAT IS RESPIRATION? It is a physic-chemical process that involves intake of oxygen by cells, oxidation and breaking down of C-C bonds of respiratory substrates of food, mainly glucose (but also sugars, organic acids, fats and proteins) with the release of CO2, H2O and energy and storage of released energy in the form of ATP. What is cellular respiration (biochemical process)? The process of oxidative breakdown of food materials within the cell to release energy trap it in the form of ATP is called cellular respiration. ATP is energy currency of the cell It consists of three components: 1. Adenine (nitrogenous base) 2. Ribose (5-carbon sugar or pentose sugar) 3. Phosphate (3 chains of phosphate groups)
  • 8. ADENOSINE TRIPHOSPHATE • Our body stores energy in the form of ATP • ATP made up of 1 adenosine molecule and 3 phosphate molecules Energy • Our body requires energy, this energy comes from the breakdown of ATP in our cells. • All energy for cellular activity comes from ATP.
  • 9. ATP Energy is released when the phosphate bond is broken.
  • 10. HOW ATP IS GENERATED? • Our cells can’t get energy directly from food • Needs to be stored as a useable form of energy ATP • The food we eat contain energy (kilojoules) • This energy is used to produce ATP molecules • Energy is stored in ATP like a battery.
  • 11. ATP IS LIKE A BATTERY FOR THE BODY is broken down to Glucose Fatty acids Amino acids Body uses ATP when it needs to Continuously recharging the battery ATP Energy released from breakdown of glucose is stored in an ATP Molecule
  • 12. NUTRIENTS–RESPIRATORY SUBSTRATES 3 types of nutrients we can get energy from • Carbohydrates • Proteins • Fats • We digest these nutrients to convert them to other forms so we can used them to generate ATP • Carbohydrates glucose ATP • Proteins amino acids ATP • Fats fatty acids ATP
  • 13. Respiratory substrate Respiratory Substrate Organic substance which are catabolised to release energy inside living cell 1.Carbohydrate 2.Fats 3.Protein Floating respiration Protoplasmic respiration
  • 14. TRUE OR FALSE • Glucose is the only useable form of energy our body can use. False! • ATP is the only useable form of energy ATP is the energy currency of the cell. Justify
  • 15. ENERGY SYSTEMS • There are three energy systems responsible for manufacturing ATP and there are two essential ways for ATP to be produced: •The Aerobic Pathway •The Anaerobic Pathways
  • 16. AEROBIC ENERGY SYSTEM • Continuous exercise lasting longer than 5 minutes like marathon, long distance cycling. Aerobic energy system-when is it used? • Most efficient energy system- also slowest • Can generate ATP in the presence of oxygen. • Is used for long distance events or exercises lasting longer than 5 minutes.
  • 17. • Based on oxidation of food in the presence or absence of oxygen (two types of cellular reparation): 1. Aerobic cellular respiration • Occurs in mitochondria of most cells (animals and plants) in presence of more oxygen. • Organisms undergoing aerobic respiration are called aerobes Two phases of aerobic respiration: 1. Glycolysis or anaerobic phase • Take place in cytosol of the cell • One glucose molecule is broken down into two molecules of pyruvic acid 2. Krebs cycle or aerobic phase • Take place in mitochondria in presence of oxygen • Pyruvic acids formed during glycolysis is completely broken down into carbon dioxide and water Types of cellular Respiration
  • 18. Aerobic cellular respiration Catabolic process Complete oxidation (water and carbon dioxide are end product)  common substrate = Glucose Glucose is derived from starch (hydrolysis) and sucrose by enzymic action. 40% of the energy in glucose is used to make ATP (aerobic is efficient) Any energy not used to produced ATP is lost as heat. Starch + maltose Glucose Sucrose + Glucose + Glucose H2O H2O Amylase Maltase Invertase
  • 19. WHY? 38 ATP MOLECULES IN AEROBIC RESPIRATION • Complete breakdown of food due to presence of oxygen • There is final hydrogen acceptor due to production of water, therefore, the ETC take place. • Hence, produce 38 ATP molecules from one glucose molecule
  • 20. 2. Anaerobic cellular respiration • Occurs in cytosol of the cell in absence of oxygen • Incomplete oxidation of food • Occurs in lower organisms (yeast, certain bacteria and fungi), hence called anaerobes. • Occurs in higher animals and plants (when oxygen is limited) • Produce only 2ATP molecules or 59 kcal from one glucose molecule. Two types of cellular respiration cont. Beaking down of Pyruvic acid 1. In yeast, bacteria and some plants Pyruvic acid (C3H4O3) Enzymes Ethyl alcohol + Carbon dioxide (Alcoholic fermentation) 2. In anaerobic animals Pyruvic acid (C3H4O3) Enzymes Lactic acid (Lactic acid fermentaion)
  • 21. WHY? ONLY 2 ATP MOLECULES IN ANAEROBIC RESPIRATION • Incomplete breakdown of food as no oxygen • No final hydrogen acceptor because water is not produce), therefore, the ETC cannot take place • Hence, produce only 2 ATP molecules from one glucose molecule • Glucose is converted to 2 molecules of pyruvate in glycolysis • NAD is reduced to NADH • There is a net production of 2 ATP
  • 22. THERE ARE TWO ALTERNATE PATHWAYS 1. Ethanol pathway 2. Lactate pathway Ethanol pathways/alcoholic fermentation • This occurs in some plants and yeast • It takes place in the cytoplasm.
  • 23. ETHANOL PATHWAYS/ALCOHOLIC FERMENTATION • Glycolysis occurs in the cytoplasm • ATP is being made, even though it is in a small amount • NAD is reduced • Pyruvate is decarboxylated to ethanal • The CO2 given off here is what makes bread rise when dough is mixed with yeast.
  • 24. ETHANOL PATHWAYS/ALCOHOLIC FERMENTATION • Ethanal is reduced to ethanol using hydrogen from NADH. The enzyme required for this process is called dehydrogenase.
  • 25. THE LACTATE PATHWAY • This occurs in mammalian skeletal muscle during exertion • When pyruvate from glycolysis is produced faster than it can be oxidized in the Krebs cycle. • This is because the supply of oxygen cannot meet the demand. • Pyruvate acts as the hydrogen acceptor. It accepts hydrogen from NADH. • NADH can go back to NAD+ and keep glycolysis going. • Pyruvate is converted to lactate by lactate dehydrogenase.
  • 26. THE LACTATE PATHWAY • ATP is made in small amounts by glycolysis • The skeletal muscles can continue to work. • Lactate is toxic and must be removed. This pathway can be reversed but needs oxygen. • An oxygen debt therefore exists. • Lactate is carried in the blood from the muscles to the liver. • 20% is oxidized to CO2 and H2O • 80% is converted to glycogen and stored.
  • 27. LACTIC ACID ENERGY SYSTEM • Also known as the anaerobic energy system • Breaks down glucose and glycogen to form ATP • Generating ATP through this energy system also produces lactic acid • Lactic acid causes our body to fatigue. • Therefore can only be used for exercise lasting 2-3 minutes • Lactic build up makes muscles feel heavy and tired. When is it predominantly used? • Intense exercise lasting 2-3 minutes • 400-800m run • Many team sports- netball, football, etc.
  • 28. METABOLIC PATHWAY 1. Carbohydrate metabolic pathway 2. Protein metabolic pathway 3. Lipid metabolic pathway • All the metabolism are taking place in cellular respiration. Why cellular respiration? • The idea of cellular reparation is to use all macromolecules to generate energy. • All the macromolecules (carbohydrates, proteins and fats) contain energy that was made by plants undergoing photosynthesis.
  • 29. CARBOHYDRATE METABOLIC PATHWAY 1. Glycolysis • Convert glucose into pyruvate or pyruvic acid 2. Pyruvate Dehydrogenase complex • Decarboxylation—conversion of Pyruvic acid into Acetyl CoA in mitochondrial matrix. • What is decarboxylation? • The removal or release of one CO2 molecule from the pyruvate (meaning one carbon is released to form acetyl CoA. • Why carboxylation is important? • Because pyruvate cannot enter into Krebs cycle, only acetyl CoA molecule get inside the Krebs cycle. • Only Acetyl CoA and Krebs cycle let cell to undergo aerobic respiration. 3. Krebs cycle • Acetyl CoA oxidized (O2) into ATP, NADH and FADH2 4. Electron transport system • Electron carriers (NADH and FADH2) produce more ATP
  • 30. Major steps involved in aerobic respiration 1. Glycolysis 2. Oxidation of pyruvate to acetyl CoA 3. Krebs cycle 4. Electron transport chain 5. Oxidative phosphorylation
  • 31. 1. GLYCOLYSIS OR EMP PATHWAY (EMBDEN'S MEYERHOF AND PARNAS PATHWAY) Where? • The cytosol What? • Breaks down glucose to pyruvic acid or pyruvate. • Glycolysis is called common pathway for both cellular respiration 10 successive reactions @Sherab Tenzin/OCS-2022
  • 32. GLYCOLYSIS • During this process one molecule of glucose (6 carbon molecules) is degraded into two molecules of pyruvate (3 carbon molecules). • Free energy released in this process is stored as 2 molecules of ATP and 2 molecules of NADH.
  • 33. 1. Glycolysis or EMP pathway (Embdens Meyerhof and Parnas Pathway)  By German scientists—Embden's, Meyerhof and Parna in 1930s.  Glycolysis is called the common pathway because initial steps of glycolysis are common to both aerobic and anaerobic respiration. Steps for glycolysis: A. Energy spending phase (Preparatory phase)/Priming Three reactions occur in the conversion of glucose to fructose 1, 6-biphosphate. 1. Phosphorylation of glucose (First phosphorylation)
  • 34. Steps for glycolysis: 2. Formation of fructose 6-phosphate 3. Formation of fructose 1, 6-biphosphate (second phosphorylation) B. Splitting phase (Splitting and rearrangement phase) 4. Lysis or splitting • Fructose 1, 6-biphosphate splits up to form one molecule of each 3-carbon compounds Glyceraldehyde 3- phosphatte (3-phosphoglyceraldehyde=PGAL) and dihydroxy acetone 3-phosphate (DiHAP). Glycolysis or EMP pathway (Embdens Meyerhof and Parnas Pathway)
  • 35. Glycolysis or EMP pathway Steps for glycolysis: 5. Isomerization of DiHAP C. Energy Conserving Phase (Pay off phase/Energy Extraction) 6. Oxidation and phosphorylation • PGAL is oxidized by the action of enzyme glyceraldehyde phosphate dehydrogenase (phosphoglyceraldehyde dehydrogenase) by removing of hydrogen and addition of phosphate to form 1, 3-biphosphoglyceric acid. • NAD+ is hydrogen acceptor. It picks up hydrogen from glyceraldehyde 3-phosphate and produces NADH + H+
  • 36. Steps for glycolysis: 7. Substrate level phosphorylation (formation of ATP) 1, 3-biphosphoglyceric acid transfers one phosphate group to ADP and changes to 3-phosphoglycerate in presence of enzyme phosphoglycerate kinase. 8. Isomerization or rearrangement • 3-phosphoglycerate is changed to its isomer 2-phosphoglycerate in presence of enzyme phosphoglyceromutase 9. Dehydration • 2-phosphoglycerate loses water in presence of enzyme enolase and changes into phosphoenol pyruvate. It undergoes molecular rearrangement and its-PO4 group is changed to high energy phosphate bond. Glycolysis or EMP pathway
  • 37. Glycolysis or EMP pathway @Sherab Tenzin/OCS- 2022 Steps for glycolysis: 10. Formation of pyruvate and substrate level ATP synthesis • High energy phosphate group of phosphoenol pyruvate is transferred to ADP with help of enzyme pyruvate kinase. This produces pyruvic acid or pyruvate and a molecule of ATP.
  • 38. Glucose (6C) Glucose 6-phosphate (6C) Fructose 6-phosphate (6C) Fructose 1, 6-Biphosphate (6C) Glyceraldehyde- 3-phosphate (3C) 1, 3 Biphosphogylceric acid (3C) 3- Phosphogylceric acid (3C) 2- pyruvic acid Phosphoenol pyruvate Dihydroxy Acetone Phosohate (3C) ATP ADP Hexokinase, Mg2+ phosphohexoisomerase, Mg2+ ATP ADP phosphofructokinase, Mg2+ NAD+ NADH + H+ Aldolase Glyceraldehyde phosohate dehydrogenase Phosphoglycerate kinase, Mg2+ ADP ATP phosphoglyceromutase 2- Phosphogylceric acid (3C) Enolase H2O Pyruvate kinase, Mg2+, K+ ADP ATP Glycolysis or EMP Energy spending phase Pay off phase/Energy exraction
  • 39.
  • 40. Net product of glycolysis Glucose Glucose 6- phosphate (1ATP is used)—Step 1 Fructose 6-phosphate Fructose 1, 6-biphosphate(1ATP is used)—step 3 1, 3-Biphosphoglyceric acid 3-phosphoglyceric acid (2 ATP is produced)-step 7 2- Phosphoenol pyruvic acid pyruvate (2ATP is produced)—Step 10 Net gain is = 4 - 2 = 2ATP 2. Each NADH produces 3 ATP: 2NAD + 2H+ +4e 1. 2NADPH 2NADPH 2x3=6ATP So net gain in glyvolyis is 6ATP + 2 ATP= 8ATP How many ATP is produced at the end of Glycolysis? • This process reduces the co-factor NAD+ to NADH. • This is important, as later in the process of cellular respiration, NADH will power the formation of much more ATP through the mitochondria’s electron transport chain.
  • 41. 2. Oxidation or oxidative decarboxylation of pyruvate to acetyl CoA • Pyruvate generated in glycolysis gets into the mitochondria through specific transport protein Coenzyme A. • Pyruvate undergo oxidative decarboxylation • Reaction is catalyzed by pyruvate dehydrogenase and several coenzymes like, NAD+, coenzyme A (CoA), thiamine pyrophosphate (TPP), lipoic acid, transacetylase and Mg2+ etc. • Glycolysis link with Krebs cycle, hence it is called link/transitional reaction or gateway step. -Glycolysis -Krebs cycle (Waste) Oxidation (to ETC) (use in Krebs cycle) • Pyruvate is oxidized in to acetate • NAD+ is reduced into NADH
  • 42. 2. OXIDATION or OXIDATIVE DECARBOXYLATION OF PYRUVATE TO ACETYL CoA • Oxidative decarboxylation, sometimes referred to as the link reaction or the transition reaction, is the link between glycolysis and the citric acid cycle. • Pyruvate is transferred into the mitochondrial matrix via a protein known as pyruvate translocase. Here, the pyruvate is combined with Coenzyme A to release a carbon dioxide molecule and form acetyl-CoA. Hence, called decarboxylation. • This transition reaction is important because acetyl-CoA is an ideal fuel for the citric acid cycle, which can in turn power the process of oxidative phosphorylation in the mitochondria, which produces huge amounts of ATP. • More NADH is also created in this reaction. This means more fuel to create more ATP later in the process of cellular respiration.
  • 43. Digestive Glands 3. Krebs cycle or Tricarboxylic Acid (TCA) Cycle • Where? • What? • In the mitochondria • Uses Acetyl CoA to generate ATP, NADH, FADH2 and CO2.
  • 44. KREBS CYCLE OVERVIEW • The Krebs cycle is contained within mitochondria. Within the mitochondrial matrix, the reactions of the Krebs cycle adds electrons and protons to a number of electron carriers, which are then used by the electron transport chain to produce ATP. • The Krebs cycle starts with the products of glycolysis, which are two three-carbon molecules known as pyruvate. • This molecule is acidic, which is why the Krebs cycle is also called the tricarboxylic acid cycle (TCA). Throughout a number of reactions, these molecules are further broken down into carbon dioxide. • Energy from the molecules is moved to other molecules, called electron carriers. These molecules carry the stored energy to the electron transport chain, which in turn creates ATP. • Altogether, the Krab's cycle consists of 9 sequential reactions.
  • 45. KREBS CYCLE PRODUCTS • Acetyl CoA is utilized within the Krebs cycle to produce several major products. In turn, these products then drive the formation of ATP, the cell’s main energy source. • Before the first stages of the Krebs cycle, pyruvate is converted into acetyl CoA. During this process, one molecule of CO2 and one molecule of the electron carrier NADH are produced. • The Krebs cycle involves converting this acetyl CoA into carbon dioxide. • During the steps of the cycle, two molecules of CO2 are released, in addition to 3 more molecules of NADH, one of FADH2, and one of GTP.
  • 46. SO, FOR EVERY 1 PYRUVATE MOLECULE ADDED, THE KREBS CYCLE WILL PRODUCE: • 2 molecules of CO2 • 3 molecules of NADH • 1 molecule of FADH2 • 1 molecule of GTP • A molecule of glucose contains 2 pyruvate molecules, so 1 glucose molecule will produce double the amount of products listed above as it moves through the Krebs cycle. These products will then be converted to ATP in later stages of aerobic respiration. Carbon dioxide is the only “waste” product and must be removed from the cell.
  • 47. 3. Krebs cycle or Tricarboxylic acid (TCA) cycle • Steps were studied by English biochemist Hans A. Krebs • Cycle is also known as citric acid cycle as the initial product formed is citric acid (C6H8O7). It has following steps: (1) Condensation or formation of citrate(6-carbon compound) • Acetyl CoA reacts with Oxaloacetate (C4H4O5) forming a 6-carbon compound called citrate in presence of condensing enzyme called citrate synthetase. (2) Isomerization (formation of isocitrate) • Citrate undergoes reorganization forming a 6-carbon compound called cis-aconitate in presence of enzyme called aconitase. Water also release here. • Cis-aconitate further reorganized into 6-carbon isocitrate in presence of enzyme aconitase, with addition of water.
  • 48. 3. Krebs cycle or Tricarboxylic acid (TCA) cycle • It has following steps cont.: (3) Second oxidative decarboxylation (Formation of α-ketoglutarate) 5-carbon compound: • Isocitrate undergoes oxidative decarboxylation forming oxalosuccinate in presence of enzyme called isocitrate dehydrogenase and Mn2+. Oxalosuccinate undergoes decarboxylation forming 5-compound called α- ketoglutarate. (4) Third oxidative decarboxylation of α-ketoglutarate • α-ketoglutarate undergoes dehydrogenation and decarboxylation together in the presence of enzyme called α- ketoglutarate dehydrogenase complex. • This complex contains TTP, lipoic acid, Mg2+ and transsuccinylase. Here, NAD+ and CoA also required.
  • 49. 3. Krebs cycle or Tricarboxylic acid (TCA) cycle @Sherab Tenzin/OCS- 2022 • It has following steps cont.: (5) Synthesis of ATP/GTP • Succinyl CoA undergoes reaction in presence of enzyme succinate or succinyl CoA synthetase thiokinase forming 4-carbon compound called succinate. • In this reaction it releases energy to form ATP or GTP. (6) Dehydrogenation oxidation of succinate: • The succinate is dehydrogenated to a 4-carbon compound called fumarate in presence of enzyme succinate dehydrogenase and 2-hydrogen atoms are released. • Hydrogen atoms are received by FAD (Flavin adenine dinucleotide) and reduced to FADH2.
  • 50. 3. Krebs cycle or Tricarboxylic acid (TCA) cycle @Sherab Tenzin/OCS- 2022 It has following steps cont.: (7) Hydration of fumarate: • Here, fumarate changes to a 4-carbon compound called malate in presence of enzyme fumarase and water. (8) Oxidation of malate or Dehydrogenation: • Malate is oxidized or dehydrogenated to oxaloacetate in presence of NAD+ and enzyme malate dehydrogenase. In this reaction, 2 hydrogen atoms are released to form NADH+H+
  • 51. Krebs or Tricarboxylic acid (TCA) cycle Steps of TCA tOxalosuccinate 3. 2nd oxidative Decarboxylation 1. Condensation/formation of citrate 2. Isomerisation 4. 3rd oxidative decarboxylation 5. Synthesis of ATP/GTP 6. Dehydrogenation oxidation of succinate 7. Hydration of fumarate 8. oxidation of malate
  • 52. III. Summary of krebs cycle or TCA cycle 1 2 3 4 1. Introduction of CoA initiates TCA 2. 3 molecules of water used and released one 3. Complete oxidation of CoA released 2 molecules of CO2 4. Four oxidation (4 H+) 3NAD+ H+ =3NADH + H+ FAD + H+ = FADH2 5. One molecules of GTP is released 6. Oxaloacetate is regenerated
  • 53.
  • 54. Mnemonic—intermediate and enzymes Cook—citrate synthetase Again—Aconitase In—Isocitrate dehydrogenase Another—alpha-ketoglutarate dehydrogenase Super—Succinyl CoA synthetase Stove—succinate dehydrogenase For—Fumarase Me—malate dehydrogenase Can—citrate or citric acid I—isocitrate Keep—Ketoglutarate Some—succinyl CoA Sugar—Succinate For—Fumarate Myself—Malate Only—Oxaloacetate
  • 55. iii. Significance of krebs cycle 1. TCA is the major pathway for releasing the energy (out of 36/38, 30 ATP is released by TCA) 2. Provides common pathway for oxidation of carbohydrates, fatty acid and amino acid 3. Intermediate products of TCA provide raw materials for anabolic pathways: i. Acetyl CoA = fatty acid, gibberellins etc,. ii. A-ketoglutaric acid = glutamic acid iii. Succinyl CoA = cytochrome, phytochrome and pyrrole ring of chlorophyll iv. Oxaloacetic acid = amino acid asparate
  • 56. SIGNIFICANCE OF KREBS CYCLE • Without Krebs cycle—not generate electron donors such as FADH2 & NADH. • In Krebs cycle no generation of any single ATP molecule, therefore, the primary function is to provide ATP energy. • It is the common pathway for the oxidation of carbohydrate, lipids and protein via acetyl CoA or intermediate of the cycle. • Citric acid cycle is an amphibolic process i.e. it plays role in both oxidative (catabolic) and synthetic (anabolic) processes. • E.g.: catabolism occurs when the citric acid cycle oxidizes the two carbon atoms of acetyl CoA to carbon dioxide (CO2). • Anabolism occurs when the citric acid cycle generates reduced factors such as NADH and FADH2.
  • 57.  Occurs at the end of the metabolic reaction of aerobic respiration.  It involves direct reaction between oxygen and hydrogen producing water. Terminal oxidation is the final steps of aerobic respiration and involves two major stteps: 1.Transport of electron 2.Oxidative phosphorylation NADH + H+ NAD + 2H+ + 2e- FADH2 FAD + 2H+ + 2e- 𝟏 𝟐 O2 + 2H+ 2e- H2O Terminal Oxidation
  • 58. ELECTRON TRANSPORT/RESPIRATORY CHAIN What? • It is the transfer of electrons from NADH and FADH2 to oxygen via multiple protein carriers. • Location of ETC—it is embedded in the mitochondrial membrane. • In the ETS—it consists of series of electron carrying molecules (5 enzyme complexes) 1. Complex I—NADH dehydrogenase/ubiquinone oxidoreductase 2. Complex II—succinate dehydrogenase/ubiquinone oxidoreductase 3. Complex III—ubiquinone cytochrome C oxidoreductase 4. Complex IV—cytochrome C oxidase 5. Complex V—ATP synthase—for oxidative phosphorylation (complex V is not participate in electrons transportation)—it is to synthesize ATP molecules Take part in ETC
  • 59. ELECTRON TRANSPORT/RESPIRATORY CHAIN • All the 5 enzyme complexes are part of inner mitochondrial membrane. • Only 4 protein complexes I, II, III and IV take part in electron transportation from one complex to another complex but complex IV take part in synthesizes of ATP molecules by under going oxidative phosphorylation. • The polypeptides of complexes originate from the 13 proteins encoded by mitochondrial DNA and from nuclear encoded proteins. • Other functions of mitochondria: • Apoptosis • Production of reactive O2 species • Calcium homeostasis • Immunity process
  • 60. ROLE OF ETS/RC • Carbohydrate into pyruvate + 2ATP + NADH—Glycolysis (anaerobic respiration). • Pyruvate into Acetyl CoA—Decarboxylation (PDH complex). • Acetyl CoA into energy rich compound such as NADH and FADH2) • Since, there is no ATP production in Krebs Cycle (TCA cycle), hence, ETC is very important to convert energy rich compound produced in glycolysis and Krebs cycle (NADH & FADH2) in to ATP molecules. • The electrons derived from NADH and FADH2 will transfer to carrier protein complexes and finally to O2 molecules inside the mitochondrial matrix. As a result, ATP molecules synthesis from ADP by undergoing an oxidation/reduction reaction (redox reaction). • ATP is used by the cell as the energy for metabolic processes for cellular functions.
  • 61. WHY ETC? • 70% of Oxygen consumed by body cells is used by ETC to produce ATP. • Finally, electrons donated by NADH and FADH2 are accepted by oxygen to generate currency energy called ATP (Adenosine triphosphate).
  • 62. IMPORTANCE OF ECT • Without Krebs cycle, not generate electron donors (FADH2 & NADH). • In Krebs cycle, no generation of any single ATP molecule. Only one molecule of GTP is produced. • In Krebs cycle only produce more and more NADH and FADH2 molecules. • Whereby, NADH and FADH2 are further energize to produce more ATP molecules. • 1 molecule of NADH produces 2.5 ATP molecules. • 1 molecule of FADH2 produces 1.5 ATP molecules. Hence, ECT is very important.
  • 63. WHERE DOES THE ETC OCCUR? • ETC and ATP synthesizing system are located on inner mitochondrial membrane. • Inner mitochondrial membrane is rich in proteins. Component of ETC: 1. Electron acceptor—NADH and FADH2 2. Complexes 3. Mobile electron carrier i. FMN ii. Co-Enzyme Q or ubiquinone iii. Iron-sulfer protein (Fe-S)—associated with FMN & Cytochrome b iv. Cytochromes (heme proteins) a. b b. c1 c. c d. a e. a3
  • 64.
  • 65. TYPES OF CYTOCHROMES • Only cytochrome c is water soluble and diffuses easily. Therefore, it plays an important role in programmed cell death (apoptosis—programmed cell death). • Cytochrome b, cytochrome c1 and cytochrome a and a3 are lipid soluble, therefore they are fixed components of inner mitochondrial membrane and they are part of electron complexes. • Cytochrome a and a3 together also called cytochrome oxidase (they also contain copper). • Co-Q and cytochrome c—are not the part of the inner mitochondrial membrane. Therefore, not the part of complexes. Located outside the inner MM. They just act as electron acceptor or electron carrier. • Complex I, II, III and IV—are part of inner MM. They are arranged in order of increasing
  • 66. WHAT IS INCREASING REDOX POTENTIAL? • When electrons flow from a negative redox reaction to a positive redox reaction. • Electrons always travel from reactants with negative redox potential (electronegative) to positive redox potential (electropositive). Therefore, complex I has –ve redox potential and complex IV has more +ve redox potential. • Due to redox potential difference between complexes, electrons always flow from complex I to complex IV. • Redox potential is main factor for the transportation of electrons because the reactant with –ve redox potential is the best donor and reactant with +ve redox potential is the best acceptor. • Low redox potential (-ve)—electron donor • Hight redox potential (+ve)—electron acceptor
  • 67. PROCESS OF ELECTRON TRANSPORT SYSTEM A. Electron acceptors—hydrogen ions and electrons produced in mitochondrial matrix are picked up by two hydrogen acceptors coenzymes. i. NADH—nicotinamide adenine dinucleotide—NADH pathway ii. FADH2-Flavin adenine dinucleotide—FADH2 pathway By picking up hydrogen ions NAD and FAD are reduced to NADH+H+ and FADH2 B. Complexes 1. Complex I—it is also called NADH dehydrogenase-ubiquinone oxidoreductase • NADH produced from PDH complex and TCA cycle transfer electrons to complex I. • NADH enter the complex I and receives electrons from NADH. • In complex I present FMN, which receives e- and transfer e- to Fe-S protein. • From Fe-S e- are transferred to Co-Q. Once electrons are transferred to Co-Q, during this stage, 4H+ are pumped into intermembrane space of mitochondria.
  • 68. PROCESS OF ELECTRON TRANSPORT SYSTEM B. Complexes 2. Complex II—it is also called succinate dehydrogenase-ubiquinone oxidoreductase (key enzyme of TCA cycle—only enzyme located in inner mitochondrial membrane) • In complex II, electrons are transfer for FADH2 to complex II and to Co-Q, and then to complex III. • But in FADH2 pathway (route II) no protons (hydrogens ions) are pump into intermembrane space. 3. Complex III—it is also called as ubiquinone cytochrome c oxidoreductase • Complex III contains cytochrome b, c1 and Fe-S. • Here electrons are transfer from cytochrome b to Fe-S and to cytochrome C1. • At this point, again 4H+ (protons) are pumped into intermembrane space.
  • 69. PROCESS OF ELECTRON TRANSPORT SYSTEM B. Complexes 4. Complex IV—it is also called as cytochrome c oxidase. Why it is called as oxidase? • Because it uses molecular oxygen to accept electrons which are donated by cytochrome c. • Cytochrome C transfer electrons to complex IV. • In complex IV—it contains cytochrome a and cytochrome a3 (it also called Heme aa3 and copper A & copper B centre). • Oxygen is the final electron acceptor in ETC. • Electrons are transfer from cytochrome C to cytochrome a, then to cytochrome a3, finally to oxygen molecules. • When electrons are accepted by oxygen, it forms water. • In complex IV—2 protons are pumped into intermembrane. @Sherab Tenzin/OCS- 2022
  • 70. TWO ROUTE/PATHWAY OF ETS 1. Route I—it also called NADH pathway • Here, electrons are transfer from NADH to complex I • Total of 8 electrons are pumped through NADH pathway into intermembrane space. 2. Route II—it also called FADH2 pathway • Here, electrons are transfer from FADH2 to complex II • Total of only 4 protons are pampered through FADH2 pathway into intermembrane space.
  • 71. NUMBER OF PROTONS IN INTERMEMBRANE SPACE If ETC starts with NADH—10 protons If ETC starts with FADH2—6 protons Therefore, NADH pathway (route I) is better than FADH2 (route 2), because there is difference in production of ATP in the body.
  • 72. COMPLEX V—ATP SYNTHASE • It is component of oxidative phosphorylation. • It is the smallest molecular motor in the body. • Due to pumping of protons into the intermembrane space, it creates electro- chemical proton gradient across the inner mitochondrial membrane. • There is high proton gradient in intermembrane space and low proton gradient in the matrix. Therefore, protons flow from high gradient to low gradient through complex V (F1 to F0) and produce ATP molecules. • Where ADP + iP—ATP in F1 subunit. • Every 4H+ protons = 1 ATP molecules.
  • 73. NUMBER OF ATP GENERATE IN MITOCHONDRIA NADH pathway—10 protons =4+4+2 =1+1+0.5=2.5 ATP molecules FADH2 pathway—6 protons =4+2 =1+0.5=1.5 ATP molecules Therefore, NADH pathway produced more ATP molecules than FADH2 pathway.
  • 74. Substrat e FA D FMN Co-Q e- from FADH2 e- from NADH+ + H Complex II-Route- 2 Complex I-Route-1 No H+ (proton) 4H+ (proton) Complex III—Cytochrome b. c1 Cytochrome c Complex IV—Cytochrome a. a3 O2 + 2H+ = H2O 4H+ (proton) 4H+ (proton) 2H+ (proton) 2H+ (proton) 2e- 2e- 2e- 2e- 2e- 2e- Route of ETC
  • 75. • Electrons enter the ETC through two routes: 1. FMN (complex I)—route 1 2. FAD (complex II)—route 2 • Both routes converge at coenzyme Q (accept electrons). Events: 1. NADH + H + formed in pyruvic acid oxidation and in Krebs cycle transfers its electrons and H + ions to FMN (first electron carrier in route 1 of ETC). In this transfer, • NADH is oxidized • FMN is reduced to FMNH2 . • NAD is again used in the reaction of pyruvic oxidation and TCA cycle. 2. Electrons from succinic acid in Krebs cycle are picked by FAD (first electron carrier in route 2 of ETC). • The reduced coenzyme Q (ubiquinone) is then oxidized by transfer of electrons to cytochrome c via cytochrome b-c complex (complex III). • The reduced cytochrome c (the mobile carrier) then transfer electrons to complex IV (the cytochrome c oxidase complex). Mechanism of transport of electrons and protons and redox potential
  • 77. • The electron transferring reactions are called oxidation- reduction reaction or redox reaction. • The electron donor and electron acceptor form redox pair. • Electron flow from the high electronegative components to the high electropositive components. • A compound which is a reducing agent in one reaction becomes an oxidizing agent in another. What is redox reaction?
  • 78. • Peter Mitchell proposed chemiosmotic theory to explain the OP. • The Synthesis of ATP from ADP and inorganic phosphate (iP) in F0 – F1 particles of ATP synthetase in mitochondria is called oxidative phosphorylation.  Transport of electrons from one molecule of NADH + H+ over ETC helps in the transport of 10 protons from intermembrane space to mitochondrial matrix and this generates 2.5/3 ATP molecules.  Transport of electrons from one molecule of FADH2 helps in the transport of 6 protons and generates 1.5/2 ATP molecules. ATP synthetase consists of two major components: 1. F0 or Base piece 2. F1 or Head piece What is Oxidative phosphorylation?
  • 79. Elementary particles or Oxysomes or Fo – F1 or Rackers particles embedded in inner Mitochindrial membrane.
  • 80. 1. Head 2. Base 3. Stalk Each oxysomes is differentiated into: Function as enzymes: ATPase ATP=ADP  Center for ATP synthesis during oxidative phosphorylation  Base piece has roter and stator  Has channel between called proton tunnel  Embedded in lipid bilayer
  • 82. • F0 piece provides channel for proton to cross inner membrane and reach to F1 piece. • F1 piece is site for ATP synthesis • ATP synthesis depends on the proton gradient in the F0– F1 particle, higher at F0 and lower at F1 • Proton gradient activates ATP synthetase in the F1 particle • Passage of a pair of proton in F0 – F1 particle produce one ATP molecule. • This hypothesis of ATP synthesis is called Chemiosmotic coupling hypothesis ATP Synthesis
  • 83. CHEMIOSMOTIC THEORY • The transport of electrons from inside to outside of IMM is accompanied by the generation of a proton gradient across the membrane. • Protons (H+) accumulate outside the membrane creating an electrochemical potentia difference. • The protons pumps (complexes I, III, IV) expels H+ from inside to outside of the membrane. • So there is high H+ concentration outside. This causes H+ to enter into mitochondria through the channels (F0-F1 complex), this proton influx binds to oxygen of Pi + ADP to form ATP.
  • 84.
  • 86. CURRENT CONCEPT OF ATP SYNTHESIS • Proton gradient is created across the IMM till the electrons are transferred to oxygen to form water. • This electrochemical potential of this gradient is used to synthesize ATP.
  • 87. RECENT CONCEPT OF: SITES OF ATP SYNTHESIS • Traditionally between complex I and coenzyme Q- First site • Between complex III and cytochrome C-second site • At complex IV and Oxygen-third site • Now the ATP synthesis occurs when proton gradient is dissipated and not when protons are pumped out.
  • 88. Homework 1. Which type of respiration is more efficient and why? 2. Why would glycolysis be considered an inefficient energy process? 3. Why is it important to breakdown the pyruvate? 4. What is the role of oxygen in aerobic respiration? 5. Suppose that each fatty acid in a certain fat can make 9 molecules of acetyl CoA. Predict how many ATP can be made from the fatty acids in this fat. (Remember there are 3 fatty acids in the fat molecule.) 6. NADH pathway is better than FADH2 pathway. Justify. 7. ECT is more important than Krebs cycle. Why? 8. What makes electrons to flow from one complex to another?
  • 89. Any muddiest point my dear students Thank you for your attention!

Editor's Notes

  1. Haem or heme bpnd to protein is called cytrochrome Flavin= naturally occuriing nitrogenous pigments Conjuycted proten contaning flavin= flavin protein