Cellular Respiration

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Cellular Respiration
Isn’t it just breathing… Why do I care…
Haven’t you ever wondered why you need to eat, breathe, and sleep? These are all vital aspects of life that can be answered with this essential and
all-encompassing process: cellular respiration. Also, it will be on your test!
(and some more)
Krebs Cycle
Electron Transport Chain
Splicing sugar
Producing energy
Set up of the
concentration gradient
Actual production of ATP
No oxygen? No problem!
Alternative pathways!
Organisms need energy to do work, to metabolize, and to reproduce. Cellular respiration, converts carbohydrates/lipids/proteins/nucleic acids into
energy that can be used to:
● Transport molecules against a concentration gradient
● Phosphorylate an enzyme
● Regulate gene expression
Cellular respiration is a rather straight-forward recipe, although you must follow each step in order to get ATP. You’ll need glucose and oxygen to
produce carbon dioxide, water, energy, and some heat. C 6H 12O 6 + 6O 2 → 6CO 2 + 6H 2O + energy (AT P ) + heat
Cellular respiration is split up into four major redox-reaction processes that involve the transfer of energy from high-energy molecules (glucose!) to
forms of chemical energy that we can use (ATP). If you think memorizing every single intermediate and each step of the process will get you an A, you
should wake up right now. Knowing the beginning, middle, end, and all of the relationships is more important.
Cellular Respiration:
Glycolysis can be thought of as an economic venture: there is an
energy-investment phase​ and an ​energy payoff phase​. You begin
with a whole molecule of glucose that is eventually broken down
into two molecules of pyruvic acid or pyruvate (either works)
Energy investment phase:
Energy payoff phase:
Net total:
- 2 ATP
+ 4 ATP, + 2NADH, + 2 Pyruvate
2 ​ATP​, 2 ​NADH​, 2 ​Pyruvate
Energy investment phase:
1) Hexokinase​ phosphorylates glucose, making it less stable
and more likely to react. The product is G6P (not important
for a test, though)
2) G6P changes shape to become F6P, or fructose-6-phosphate
3) Phosphofructokinase​ phosphorylates F6P, making it even
less stable, and yields fructose-1,6-biphosphate.
4) Fructose-1,6-biphosphate is a very unstable molecule, so it
splits (5) into two PGAL molecules
Energy payoff phase:
1) Each PGAL is phosphorylated and reduced by ​dehydrogenase
enzymes, meaning each PGAL has been oxidized and become
2) Kinases phosphorylate ADP with ​a​ phosphate group from each
FBP, producing two ATP molecules total. ATP is generated
through ​substrate-level phosphorylation​.
3) Kinases phosphorylate ADP with ​a​ phosphate group from each
broken-down FBP, once again producing two ATP molecules
total. This is also ​substrate-level phosphorylation​.
4) After each phosphate group has been ripped off of FBP, all
that remains is ​pyruvic acid,​ or ​pyruvate​.
Key Ideas:
- Glycolysis is an ​anaerobic​ process, meaning that occurs with or without the presence of oxygen in the ​cytoplasm
- Because it is a process found in nearly all organisms, it can be assumed that a common ancestor of nearly all organisms developed this ​ancient
process as a way to use energy
- Throughout glycolysis, glucose is phosphorylated to increase its potential energy. The addition of each phosphate group makes the overall molecule
more unstable.
- ​Kinases​ transfer phosphate groups from one molecule to another (whether it be a phosphate group from ATP or from FBP)
- ​Substrate-level phosphorylation ​uses enzymes (like kinases) to phosphorylate molecules. The source of phosphate groups can be from ATP or FBP. In
cellular respiration, Kinase phosphorylates ADP to yield ATP.
- Glycolysis is a very ​efficient​ process with trade-off of 2 ATP in exchange for 4 ATP, 2 NADH, and 2 pyruvate.
- NADH is important since it is an electron carrier which will be useful in the the Citric Acid Cycle.
- Pyruvate is an energy-rich molecule that can be broken down further.
- Phosphofructokinase is an enzyme that can be managed through ​feedback inhibition​ (see Unit 1: Metabolism).
- Excess of ATP → pathway can be stopped since ATP is an allosteric inhibitor for phosphofructokinase.
- Excess of AMP → pathway can be increased since AMP is an allosteric activator for phosphofructokinase
- High ATP levels indicate sugar is already being converted into usable energy, so glycolysis can temporarily stop.
High AMP levels indicate more work than glycolysis is being done, so the rate of glycolysis increases.
Resources: ​https://www.ncbi.nlm.nih.gov/books/NBK22395/#A2246
Pyruvate Entry Complex:
The pyruvate entry complex is a series of enzymes along the inner
mitochondrial membrane/cristae that cause pyruvate to become
acetyl coA (used in Krebs cycle).
Enzymes involved:
1) Decarboxylase: removes a carboxyl group (COOH) from pyruvate (so
it goes from a 3C sugar to a 2C sugar!)
2) Dehydrogenase: an electron carrier (NAD+) is reduced to NADH
3) CoA-smush-ase: don’t need to know the formal name; all you need
is that it sticks a coA group onto pyruvate
Krebs Cycle:
Each molecule of pyruvate
is used to form electron
carriers (NADH & FADH2)
and some ATP through
substrate level
- Knowing pyruvate, acetyl,
citrate, and oxaloacetate is
- Keep in mind that for
every glucose molecule
broken down, two
molecules of pyruvate are
- Only one cycle of pyruvate
is shown, but the actual
amount yielded per glucose
is twice what is shown
- CO2 is a byproduct of
dehydrogenase working
- The ATP produced is actually GTP, or guanosine triphosphate, a similar, energy-rich molecule that can also be used to do work (but eh same thing)
- ATP is generated through​ substrate-level phosphorylation ​with the help of kinases once again
- Both NADH and FADH2 are electron carriers that transport electrons to the electron transport chain (coming up next!)
1 pyruvate → C O 2 + 3NADH + 2F ADH 2 + AT P
Key Ideas:
- The Krebs cycle is an ​aerobic​ process since it receives NAD+ and FAD from the electron transport chain, an aerobic process (you will find out soon!)
- The Krebs cycle occurs in the mitochondrial ​matrix​ where conditions can be manipulated to facilitate the cycle
- Factors like pH within an organelle can be modified to enhance the efficiency of enzymatic processes
- ​Substrate-level phosphorylation ​is used in both glycolysis and Krebs cycle to generate ATP
- The citric acid/Krebs cycle is a ​cycle​ because the end product (oxaloacetate) begins the entire cycle once again (by combining with acetyl coA to yield
the titular citrate/citric acid)
Electron Transport Chain:
What is the point of all these electron carriers? Where are they going to end up? Well, along the inner mitochondrial membrane, there are many ETC
complexes, or successions of protein complexes that set up a concentration gradient that eventually lead to the production of ATP (next!).
Key Points:
- The ETC is an ​aerobic​ mechanism of ​electronegative​ ​complexes​ each reduce the next electron acceptor. Oxygen is needed because it is the ​most
electronegative​ atom and is the ​final electron acceptor.​
- The ETC sets up a ​proton gradient​,​ or a membrane potential with the uneven distribution of protons in the ​matrix​ ​vs ​intermembrane​ ​space​.​ The
potential energy held in this gradient is used in chemiosmosis (next!)
- ↑[H+] in the intermembrane space
([ ] = concentration of)
- ↓[H+] in the matrix
- The electron carriers are a source of hydrogen atoms for the protein complexes
- ​NADH​ drops off two electrons at an enzyme and causes ​3​ H+ ions to be pumped into the intermembrane space
- ​FADH2​ ​drops off two electrons at a fatty enzyme and causes ​2​ H+ ions to be pumped into the intermembrane space
- Once the NADH/FADH2/electron carriers have dropped off their electrons and reverted back to NAD+ and FAD, they go back to the Krebs
cycle to be get more hydrogens
- Once electron carriers have dropped off their electrons, each inner membranous enzyme passes the electrons down a chain until they reach ½ O2
- Reduction of each enzyme (​exergonic​) fuels the pumping H+ ions against the concentration gradient into the intermembrane space
(​endergonic​) = energy coupling!
- H+ ions are all being ​actively transported​ into the intermembrane space in order to generate lots of potential energy/proton-motive force
from the gradient
- The redox chain of proteins stops once oxygen receives the two electrons (final e- acceptor)
- Examples of intermediates are:
- ​Flavoprotein ​(strawberry) is a hydrogen pump that pumps 3 H+ out into the intermembrane space when reduced by NADH
- ​Q​ (butter) is a fatty complex that ​does not​ pump H+ into the intermembrane space ​even when reduced by FADH2
- In total, 6-9 H+ are pumped into the intermembrane space depending on which complexes are reduced:
- If NADH reduces flavoprotein, the two electrons will be pass through ​three​ hydrogen pumps, releasing a total of 9 H+ into the
intermembrane space
- If NADH reduces Q/ubiquinone (same thing), the two electrons will pass through ​two​ hydrogen pumps, releasing 6 H+ instead.
- If FADH2 reduces Q, the two electrons will pass through ​two​ hydrogen pumps and release 6 H+.
- ​Final electron acceptor:​ 12O 2 is the most electronegative component of the ETC, so all of the electrons transferred from the electron carriers to the
intermediates of the process end up with oxygen
- 12O 2 is unstable on its own, so it quickly bounds with H+ ions to form water
If the whole point of this process is to make ATP, where is all the ATP? See, this is where the true genius of evolution and biology emerge: ​oxidative
phosphorylation​ and ​chemiosmosis​.
As hydrogen ions flow down their concentration gradient, they turn the rotor-like structure of ATP synthase and phosphorylate ADP to generate ATP.
This is known as ​oxidative phosphorylation​ since the potential energy from redox-driven ETC reactions is used to generate ATP.
Substrate level phosphorylation
Oxidative phosphorylation
Enzymes are used (kinases)
Glycolysis and Krebs cycles
Smaller yield (4 ATP)
Anaerobic (glycolysis only)
Redox reactions are used
Larger yield (32-34 ATP)
Aerobic (oxygen is final electron acceptor)
For every 3H+ that pass through ATP synthase, 1 ATP is formed.
There is an inverse relationship between CO2 production and O2 consumption during cellular respiration
There is a direct relationship between the amount of ATP formed and the amount of O2 consumed
- When there is no oxygen present, Krebs and ETC cannot function
- This is because ETC is directly aerobic and needs oxygen as the final electron acceptor
- Krebs is also aerobic because the ETC regenerates electron carriers (NADH → NAD+; FADH2 → FAD). If the ETC cannot oxidize the electron
carriers from NADH back to NAD+, there is a buildup of NADH and FADH2 since Krebs can’t work.
- Glycolysis is an anaerobic process, so it doesn’t have this problem
- organisms can still generate some ATP through glycolysis, but it’s a primitive/last-ditch situation
- After glycolysis, there are two options:
1) Alcohol fermentation: pyruvate is reduced to ethanol and regenerates NAD+
2) Lactic acid fermentation: pyruvate is reduced to lactic acid and regenerates NAD+
Alcohol fermentation
Lactic acid fermentation
- Pyruvate to ethanol
- Bacteria, yeast cells
- Releases CO2
- Pyruvate indirectly reduced to ethanol
- Reduced by NADH
- ​Regenerate​ NAD+ for glycolysis (which makes ATP)
- substrate-level phosphorylation
- Pyruvate to lactate
- Humans, fungi, bacteria
- No release of CO2
- Pyruvate directly reduced to lactic acid/lactate
Catabolism of Macromolecules to Constituents of Cellular Respiration (in order of
1) Carbohydrates can be directly broken down to enter glycolysis
2) Fats must be broken down into glycerol and fatty acids which enter glycolysis and Krebs, respectively
3) Proteins must first undergo deamination (removing amine groups) to enter Krebs as acetyl coA

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