202 Krebs,TCA,oxidative Phosohirylation Flashcards
(26 cards)
State the intermediates of the Krebs cycle and explain the kreb cycle process with the enzymes involved starting from when you get pyruvate from glucose
Note that before Krebs starts, there’s something called the preparatory phase via pyruvate dehydrogenase complex before the Krebs starts. So after glycolysis, the breakdown continues in the mitochondria not the cytoplasm and that’s where the preparatory phase or transition phase starts.
So pyruvate from glycol enters the mitochondria
Note that acetyl coA can be gotten form glycolysis, amino acids,ethanol,fatty acids and ketone bodies
Krebs cycle mnemonic
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Oxaloacetate Citrate Isocitrate Alpha ketoglutarate Succinyl coA Succinate Fumarate Malate Oxaloacetate again
Or
Citrate is Krebs Starting Substrate For Making Oxacoacetate
So you get pyruvate from glucose.
1.The pyruvate is converted to acetyl coA via pyruvate dehydrogenase complex with products of NADH and CO2 . This is oxidative decarboxylation.
This step links glycolysis to Krebs cycle. But isn’t part of the Krebs cycle
2.acetyl coA (2C) is added to Oxaloacetate (4C) to produce citrate (6C) via citrate synthase.this starts the Krebs cycle that’s why citrate is the first intermediate
Note: Synthase: Catalyzes reactions without using ATP.
• Synthetase: Catalyzes reactions that require ATP.
Since citrate synthase does not use ATP to catalyze the condensation of acetyl-CoA and oxaloacetate to form citrate, it is correctly called a synthase.
- Citrate is converted to isocitrate by aconitase.
Citrate → cis-Aconitate (via aconitase, with water removed)
• Step 2: cis-Aconitate → Isocitrate (via aconitase, with water added back in a different position)
➢Aconitase is an isomerase and catalyzes an internal rearrangement of atoms and electrons. An Fe2+ cofactor facilitates in this transfer.
➢Here the hydroxy group of the citrate is moved to an adjacent carbon so it can be oxidized to form a keto group.
- Isocitrate is converted to alpha ketoglutarate via isocitrate dehydrogenase. With products of NADH and CO2
- Alpha ketoglutarate is converted to succinyl coA by alpha ketoglutarate dehydrogenase to produce another NADH and CO2
The dehydrogenase complex uses thiamine pyrophosphate and lipoic acid as coenzymes. The complex includes α-ketoglutarate dehydrogenase (E1), dihydrolipoyl transsuccinylase (E2) and dihydrolipoyl dehydrogenase (E3).
➢The reactions here are similar to that of the pyruvate dehydrogenase complex and the product is high energy thioester - succinyl CoA.
- Succinyl coA is converted to succinate via Succinyl coA synthetase or succinate thiokinase to produce GTP or ATP depending on the tissue and CO2 by substrate level phosphorylation.
In mammals, GTP is synthesized from GDP. In plants and bacteria, ATP is synthesized from ADP.
➢This reaction is an example of a substrate level phosphorylation, which is the formation of a high level phosphate bond without the use of oxygen
In liver and some tissues: it produces GTP
• In muscle and brain: it produces ATP
Here’s the clarification:
Synthetase vs. Synthase:
• Synthetase: Requires energy, usually in the form of ATP or GTP.
• Synthase: Does not require energy from ATP/GTP.
So why is succinyl-CoA synthetase still called that, even though it produces GTP/ATP?
Because it uses energy from the high-energy thioester bond in succinyl-CoA to catalyze phosphorylation of GDP/ADP — not from free ATP. That counts as an energy-requiring process, even though ATP is not the input.
It’s better understood as a substrate-level phosphorylation enzyme that uses energy released during the reaction.
So:
• It doesn’t consume ATP.
• But it uses energy (just not from ATP), so it’s classified as a synthetase.
- Succinate is converted to fumarate via succinate dehydrogenase and produces FADH not NADH. The reaction involves the oxidation of succinate to fumarate, with the reduction of FAD to FADH₂, but it does not release carbon dioxide (CO₂).
The enzyme is inhibited by malonate, which is a structural analogue of succinate. This is an example of competitive inhibition.
- Fumarate is converted to malate via fumarase
This enzyme catalyzes the hydration of the double bond of fumarate to form malate
- Malate is converted to Oxaloacetate via Malate dehydrogenase to produce NADH not co2
Due to the rapid utilization of the oxaloacetate, the reaction is more driven to the direction of oxaloacetate production.
➢The availability of oxaloacetate ensures the formation of the citrate. This is to make sure that the TCA cycle operates even at low oxaloacetate concentrations
Succinate → Fumarate) produces FADH₂ instead of NADH because succinate dehydrogenase uses FAD to accept electrons, and it’s part of the ETC in the mitochondrial membrane.
You’re right to ask for clarification. Let’s go through this carefully.
Reaction 9: Malate → Oxaloacetate
The reaction:
Malate → Oxaloacetate via Malate dehydrogenase (MDH)
• Malate is oxidized to oxaloacetate.
• During this process, malate loses two electrons (the oxidation part) and one proton (H⁺). These electrons are transferred to NAD⁺, which becomes NADH in the process.
• This results in the conversion of malate (a reduced form) to oxaloacetate (an oxidized form).
Why is it an oxidation?
• Oxidation means loss of electrons. In this case, the malate molecule loses two electrons (which are transferred to NAD⁺, turning it into NADH), and it is therefore oxidized.
• Since the reaction involves the loss of electrons and protons, it’s considered an oxidation reaction.
What about the addition of hydrogen?
• The hydrogen is part of the electron pair. The removal of two hydrogen atoms (one as a proton, H⁺, and the other as electrons, e⁻) from malate is considered oxidation.
• The hydrogen atoms are transferred to NAD⁺, forming NADH.
To sum up:
• In Reaction 8, malate is oxidized to oxaloacetate, meaning it loses electrons and protons. These electrons are accepted by NAD⁺, which becomes NADH.
• This reaction is both an oxidation (due to the loss of electrons from malate) and a dehydrogenation (because it involves the removal of hydrogen atoms).
The oxaloacetate that is consumed in the first reaction is regenerated in the last step of the cycle, thus the cycle can oxidize an unlimited number of acetyl groups
5.All enzymes involved in the TCA cycle are located in the mitochondrion so all substrates used must either be generated in the mitochondria or must be transported into the mitochondria from the cytosol
Which reactions in the TCA cycle produces NADH and CO₂?
Which reaction in the TCA cycle produces FADH₂?
Which reaction in the TCA cycle produces ATP (or GTP) via substrate-level phosphorylation?
Which reactions in the TCA cycle produce CO₂?
So in all,how many products of NaDH2,FADh,GTp and co2 are produced after Krebs cycle
This cycle produces most of the carbon dioxide in the body
Which reactions in the TCA cycle produce NADH?
A:
• Isocitrate → α-Ketoglutarate (via Isocitrate dehydrogenase)
• α-Ketoglutarate → Succinyl-CoA (via α-Ketoglutarate dehydrogenase)
• Malate → Oxaloacetate (via Malate dehydrogenase)
• These reactions all produce NADH.
Which reactions in the TCA cycle produce CO₂?
A:
• Isocitrate → α-Ketoglutarate (via Isocitrate dehydrogenase) this releases co2 cuz isocitrate is 6 carbon and alpha ketoglutarate is a 5carbon so it has lost one carbon via the release of CO2.
• α-Ketoglutarate → Succinyl-CoA (via α-Ketoglutarate dehydrogenase) • These reactions release CO₂.
Which reaction in the TCA cycle produces ATP (or GTP) via substrate-level phosphorylation?
Succinyl-CoA → Succinate via Succinyl-CoA synthetase.
• This reaction produces 1 ATP (or GTP) through substrate-level phosphorylation.
Which reaction in the TCA cycle produces FADH₂?
A: Succinate → Fumarate via Succinate dehydrogenase.
• This reaction produces 1 FADH₂.
Summary:
• 3 NADH
• 1 FADH₂
• 1 ATP (or GTP)
• 2 CO₂
Remember that glycolysis produces 2 pyruvate so in all, everything will be multiplied by 2 so
6NADH2, 2FADH2,2GTP,4CO2
Two water molecules are consumed – one to hydrolyze acetyl CoA and one to hydrate fumarate.
5.One unit of acetyl CoA generates about 10 molecules of ATPs per cycle which is more efficient than anaerobic respiration.
6.Even though molecular oxygen does not take part in the cycle, the cycle operates only under aerobic conditions.
You’re right to question that — let’s clarify it carefully.
TCA Cycle: ATP Yield Breakdown
One acetyl-CoA entering the TCA cycle produces the following electron carriers and GTP (which is ATP-equivalent):
• 3 NADH → each yields ~2.5 ATP → 7.5 ATP
• 1 FADH₂ → yields ~1.5 ATP → 1.5 ATP
• 1 GTP → considered equivalent to 1 ATP → 1 ATP
Total ATP per Acetyl-CoA:
7.5 + 1.5 + 1 = 10 ATP
This is the widely accepted value for aerobic metabolism, especially in USMLE preparation and updated biochemistry textbooks (including Harper’s and Lippincott’s).
Why 2 ATP Was Thought Previously:
Older sources sometimes only counted the 1 GTP (ATP) produced directly in the cycle, ignoring NADH and FADH₂ which are indirect ATP sources via the ETC. That’s why older materials may list “2 ATP” per cycle — which is outdated.
Would you like a flashcard version of this ATP yield breakdown?
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What happens after the Krebs cycle
Why is the conversion of isocitrate to alpha ketoglutarate the rate limiting step
What happens after the TCA cycle?
After the cycle:
1. NADH and FADH₂ go to the electron transport chain (ETC) in the inner mitochondrial membrane.
2. In the ETC, they donate electrons which power proton pumps, creating a proton gradient.
3. This gradient drives ATP synthesis via ATP synthase — this is oxidative phosphorylation.
4. Oxygen is the final electron acceptor and is reduced to water.
Even though citrate synthase (which makes citrate) is a regulated step, the true rate-limiting step is isocitrate dehydrogenase (which converts isocitrate to α-ketoglutarate). Here’s why:
Why is isocitrate dehydrogenase the rate-limiting step?
1. Tightly controlled by energy status:
• Activated by ADP (low energy)
• Inhibited by ATP & NADH (high energy)
2. Commitment step:
• Once isocitrate is converted to α-ketoglutarate, the cycle is more or less committed to completing — making this the step that determines the overall speed of the cycle.
3. Highly regulated in response to cellular needs:
• It responds quickly to changes in energy demand (e.g. exercise increases Ca²⁺, which activates it).
Why not citrate synthase?
• Citrate synthase is regulated, but:
• It doesn’t respond as sensitively to energy signals (ATP, ADP) as isocitrate dehydrogenase does.
Krebs cycle regulation
- The Citrate production via citrate synthase is an irreversible step. So it’s regulated by inhibition by ATP(allosterically). Cuz if we have a lot of ATP, we won’t need more citrate to be produced.
NADH also inhibits it cuz high NADH shows we have enough to do what we want which is anabolism of some products so we don’t need it. Citrate itself can inhibit this reaction by product inhibition. Succinyl coA is a substrate inhibitor of this step.
ADP is an activator cuz more ADP shows there’s less ATP in the body.
It’s an irreversible step because Why it’s irreversible:
• It has a large negative ΔG (i.e., it’s highly exergonic).
• It commits the acetyl group from acetyl-CoA to the cycle.
• It’s one of the key regulatory steps in the TCA cycle. - This step is reversible.
The conversion of citrate to isocitrate is inhibited by rat poison which contains fluoroacetate. This FA mimics acetyl co A so it looks like it via fluoro acetyl coA and this is combines with Oxaloacetate
to form fluoro citrate which binds to the aconitase and prevents further movement of the cycle. This leads to accumulation of citrate. Accumulation of citrate can be transported into the cytoplasm, where it signals phosphofructokinase to halt glycolysis. The citrate also serves as a source of acetyl CoA for the synthesis of fatty acids. I think inhibition of isocitrate dehydrogenase also leads to accumulation of citrate.
The enzymatic product fluorocitrate cannot be further metabolized by aconitase nor can it be transported out of the mitochondria.
- The next step is also irreversible. Literally any reaction that releases co2 is likely to be irreversible and we’ve already explained why it’s irreversible in the first point.
Isocitrate dehydrogenase has three pockets or three binding sites. Calcium (needed for muscle contractions and this needs more ATp so you’ll stimulate that enzyme to produce more NaDh to enter ETc to get more ATp) and ADP stimulate it. aTP inhibits it. - The next step is very important. Succinyl coA is 4C and alpha ketoglutarate is 5C so you’ll lose a CO2 here. The alpha ketoglutarate dehydrogenase also has three pockets or binding sites. Succinyl coA if too much S. coA and NADH can inhibit it if there’s too much NaD+. Calcium will stimulate it cuz it wants more ATP.
Note that alpha ketoglutarate is an important cofactor for histone demythelase. Histones have methyl groups on them. So the demethylase will remove those methyl groups. If there’s a mutation in the isocitrate dehydrogenase, it uses NADPH to convert alpha-ketoglutarate into 2-hydroxyglutarate (2-HG).
• 2-HG looks like alpha-ketoglutarate, but it’s a false substitute. It blocks the real function of alpha-ketoglutarate–dependent enzymes like histone demethylases and DNA demethylases. the product formed is 2 hydroxy glutarate instead of alpha ketoglutarate. This means gene expression can’t be controlled cuz there’s no alpha ketoglutarate to bind to histone demethylases.
This can lead to cancers especially gliomas.
During the reaction, α-ketoglutarate is decarboxylated to succinate and CO₂, providing the oxidation needed to break the methyl group off.
Gene Activation or Repression
• Methyl groups added to certain histone residues (like H3K9 or H3K27) repress gene expression — the DNA is tightly wound and inaccessible to transcription machinery.
• Removing these methyl groups (demethylation) loosens the DNA, making it accessible so the gene can be turned on (transcribed).
The α-ketoglutarate that accumulates when alpha keto dehydrogenase is inhibited can be used as a precursor for the synthesis of several amino acids and purine bases and also an amino acceptor during transamination reactions.
5.alpha ketoglutarate to Succinyl coA. 5C to 4C.
A co A is added to the succinyl.
You lose the coA when converting Succinyl coA to succinate and as you do so, you release energy in the form of GTP. ADP comes in and takes the phosphate from GTP becoming ATp. So the GTp is converted back to GDP. This is substrate phosphorylation and it doesn’t produce as much ATp as oxidative phosphorylation.
5.this is reversible. The enzyme that converts succinate to fumarate is anchored on the inner mitochondrial membrane specifically the cristae and it’s called complex II or succinate dehydrogenase. So this enzyme works in both the Krebs and the ETC. Uses FAD as a coenzyme. So in phaeochromocytoma,there’s a mutation in SDH or complex II and this leads to neuroblastoma formation. The phaeochromocytoma itself forms on the adrenal medulla and causes excessive amounts of epinephrine or norepinephrine to be produced leading to hypertensive crisis.
- Fumarate to Malate. Fumarase adds water to it to convert Fumarate to malate. Both 4C.
Deficiency in this Fumarase leads to leiomyomas.
You’re right to ask — the citric acid (TCA) cycle is regulated through multiple mechanisms. Here’s a breakdown of the main types of regulation:
- Allosteric Regulation
• Enzyme activity is increased or decreased by binding of effectors (activators or inhibitors) at sites other than the active site.
• Examples:
• Isocitrate dehydrogenase: activated by ADP, inhibited by ATP and NADH
• α-ketoglutarate dehydrogenase: inhibited by succinyl-CoA and NADH - Substrate Availability
• The cycle depends on the presence of substrates like:
• Acetyl-CoA
• Oxaloacetate
• NAD⁺
• Low levels of these substrates will slow the cycle. - Product Inhibition (Feedback Inhibition)
• End products inhibit earlier enzymes to prevent overproduction.
• Examples:
• Citrate inhibits citrate synthase
• Succinyl-CoA inhibits α-ketoglutarate dehydrogenase
• NADH inhibits multiple dehydrogenases - Energy Charge
• The ratio of ATP/ADP and NADH/NAD⁺ reflects the cell’s energy status.
• High ATP or NADH = slow cycle
• High ADP or NAD⁺ = activate the cycle - Calcium Activation (in muscles)
• Ca²⁺ signals energy demand in muscles.
• It activates:
• Isocitrate dehydrogenase
• α-ketoglutarate dehydrogenase
Summary Table:
Regulation Type Example
Allosteric ADP activates isocitrate dehydrogenase
Substrate availability Low Acetyl-CoA or NAD⁺ slows the cycle
Product inhibition Succinyl-CoA inhibits α-ketoglutarate dehydrogenase
Energy charge ATP/NADH inhibit; ADP/NAD⁺ activate
Calcium activation Ca²⁺ activates key enzymes in active muscle
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Note: The irreversible steps in the Krebs cycle (TCA cycle) are:
1. Citrate synthase
• Reaction: Acetyl-CoA + Oxaloacetate → Citrate
• Highly exergonic and commits acetyl-CoA to the cycle.
2. Isocitrate dehydrogenase
• Reaction: Isocitrate → α-Ketoglutarate + CO₂ + NADH
• Also the rate-limiting step of the cycle.
3. α-Ketoglutarate dehydrogenase
• Reaction: α-Ketoglutarate → Succinyl-CoA + CO₂ + NADH
• Another key regulatory and irreversible step.
These steps are highly regulated and exergonic, making them one-way reactions under physiological conditions.
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Summary:
Regulation of pyruvate dehydrogenase complex (PDC)
Covalent modification - by pyruvate dehydrogenase kinase (PD kinase), which phosphorylates a serine residue thereby inactivating the pyruvate dehydrogenase complex.
The activators are NADH and acetyl and the inhibitors are ADP and pyruvate.
Insulin, which is secreted in response to increase blood glucose, promotes increasing levels of PDC and the synthesis of acetyl CoA. Insulin inhibits by activating pyruvate dehydrogenase phosphatase which removes the phosphate group.
2.
Product inhibition by NADH and acetyl CoA - High concentrations of these products compete with NAD+ and CoA for binding sites on their respective enzymes. They also stimulate the phosphorylation reaction.
High [NADH]/[NAD+] and [acetyl CoA]/[CoA] binds to the transacetylase and the dihydrolipoyl dehydrogenase respectively and decrease the rate of pyruvate decarboxylation.
What happens to pyruvate after glycolysis ;
In the absence of oxygen
In the presence of oxygen
Anaerobic glycolysis that ends at pyruvate or lactate is wasteful for the body cuz it doesn’t produce much atp.
For more ATP, the pyruvate must be converted to a substrate that will generate more atp.
Presence: NADH sends electrons to ETC and pyruvate is converted to another molecule(acetyl CoA) to be taken into the mitochondria. So pyruvate dehydrogenase (irreversible step) adds co-A to the pyruvate, removes a carbon via CO2 and reduces nad to NADH.
Absence: NADH drops electrons on pyruvate to form lactic acid. The reaction of pyruvate to lactic acid is catalyzed by lactate dehydrogenase and takes place during intense muscle activity.
Reaction:
Pyruvate + NADH + H⁺ → Lactate + NAD⁺
Yes, exactly — lactate dehydrogenase (LDH) has five isoenzymes (LDH1 to LDH5), which are combinations of two subunits: H (heart) and M (muscle).
LDH Isoenzymes:
Isoenzyme Subunits Major Tissue Location
LDH1 (H4) HHHH Heart, RBCs
LDH2 (H3M) HHHM Heart, RBCs
LDH3 (H2M2) HHMM Lungs, lymph, platelets
LDH4 (HM3) HMMM Kidney, pancreas
LDH5 (M4) MMMM Skeletal muscle, liver
Clinical Relevance:
• LDH1 > LDH2 in blood can suggest myocardial infarction (MI) (flipped ratio).
• LDH5 elevation may suggest liver or muscle damage.
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Purpose of lactic acid fermentation in humans
If we are sprinting, exercising or need a lot of energy at short notice, the demand for oxygen and ATP in the muscle cells exceeds the ability of the respiratory system to meet demand if untrained.
This puts us in oxygen debt and to compensate, we use glycolysis to convert glucose to lactic acid, a process that (i) doesn’t require oxygen and (ii) will regenerate NAD+ from NADH to ensure continuity of the glycolytic reactions.
Lactic acid production in the body allows short-term energy production in the absence of oxygen and is thus a less effective alternative way of ATP production.
By yielding only 2 molecules of ATP per glucose breakdown, the process is not efficient
However, in strenuous exercise, it’s better to produce 2 ATP molecules per glucose rather than none when muscle cells are being called on to perform at a high rate of metabolism e.g. to allow us to run away from a dangerous situation
The lactic acid can then be transported to the liver, where it is turned back into pyruvate. However prolonged activity will result in lactic acid builds up in the skeletal muscle making them stiff and sore.
So in humans in the absence of oxygen, pyruvate is converted to lactate. In micro org, it’s converted to ethanol.
This pathway is highly relevant in anaerobic fermentation, particularly in yeast and some microorganisms, not humans.
Here’s how it works:
In yeast:
1. Pyruvate is decarboxylated (loses CO₂) by pyruvate decarboxylase → forms acetaldehyde.
2. Acetaldehyde is then reduced to ethanol by alcohol dehydrogenase, using NADH → regenerates NAD⁺, which is crucial for glycolysis to continue under anaerobic conditions.
Relevance:
• Industrial fermentation (e.g. brewing, wine-making).
• Biochemistry concept: Shows how cells regenerate NAD⁺ when oxygen is not available.
• Contrasts with lactic acid fermentation in humans, where pyruvate is converted to lactate instead of ethanol.
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Why is regulation of PDH complex important?
Why can’t we use fats to maintain blood glucose levels?
The Pyruvate dehydrogenase complex is made up of 3 individual enzymes. Name them.
State what happens for each enzyme when pyruvate is available.
What are the end products of this PDH complex?
What inhibits these enzymes in the PDH complex?
How is PDH complex regulated
Two factors that ascertain the rate of ATP utilization are the ATP/ADP and the NADH/NAD+ ratios.
5.Regulation of the pyruvate dehydrogenase complex is important because it is the only pathway in mammals for the synthesis of acetyl CoA from pyruvate.
6.It is also an irreversible step and animals cannot convert acetyl CoA back to glucose hence our inability to use fats to maintain blood glucose levels.
7.The reaction commits the two carbon atoms produce to either undergo oxidation in the TCA cycle or incorporate into lipid.
Enzyme 1,2,3(E1,2,3). E1 is pyruvate dehydrogenase
E2 is dihydrolipoamide acetyl transferase.
E3 is dihydrolipoamide dehydrogenase (due to the taking of the 2 -H from the Lipoate to the NaD)
1.In enzyme one, there is thiamine in the form of TPP. Thiamine pyrophosphate. So thiamine bound to two phosphates. (Note that so in thiamine deficiency, beriberi occurs. Leading to neurological problems. Since the nervous system relies essentially on glucose for its energy requirements, when these enzymes are inhibited, the nervous system is deprived of its source of fuel. Thiamine is a precursor for thiamine pyrophosphate, which is a prosthetic group for pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complex)
The TPP reacts with the pyruvate to release CO2. So now it’s left with 2C(acetyl group) instead of 3C.
The TPP gives the 2C to an enzyme in E2.
- Lipoate enzyme or lipoic acid is in E2. The lipoate has disulfide bonds. Lipoate reacts with TPP. The 2C is pulled and The disulfide bond breaks. The remnants of the bond is a reduced form of Lipoate. And produces -SH which stays free to accept electrons and another -SH which is bound to the 2C.
After transferring the acyl group to CoA(from B5), the lipoate is left in a reduced form (–SH and –SH).
4. It is then re-oxidized back to the disulfide form by FAD or NAD+.
So yes, in the intermediate form:
• One sulfur (S) holds the acyl group.
• The other sulfur (S) remains as a free thiol (–SH).
So at the end of E2, we have acetyl coA and the Lipoate having 2 thiol groups or 2 -SH groups. We can’t let the H from the thiol groups go to waste cuz it’s not even originally there. The original was Lipoate with 2 -S to get that disulfide bond. Not 2 -SH.
So the H must go. This is where E3 comes in.
3. FAD from B2(F before N so F is b2 and N is b3) comes to take the 2-H to form FADH2.
NAD comes to take the H from the FaDH2 to form NADH and this goes to the ETC.
Great thinking! Here’s the answer in simple terms:
NAD⁺ accepts one hydride ion (H⁻) — which is a hydrogen atom with two electrons — and becomes NADH, not NADH₂, because:
• NAD⁺ only takes 1 hydrogen atom (as a hydride: H⁻)
• The other hydrogen (H⁺) is released freely into the solution (not added to NAD⁺)
So:
• FAD + 2H → FADH₂ (FAD takes 2 H atoms — both the electrons and protons)
• NAD⁺ + 2H → NADH + H⁺ (NAD⁺ takes 1 H as a hydride, the other is released)
That’s why it’s NADH, not NADH₂.
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Products: 2CO2,2acetyl coA,2FADH2,2NADH. We used 2coA
Regulation of PDH complex-
1.PDH kinase phosphorylates E1 to inhibit it from even going to E2,E3.
High ATp ,high NADH,high acetyl coA stimulates PDH kinase and this makes PDH kinase inhibit the PDH complex. So high ATP itself doesn’t inhibit the PDH complex.
High ADP and high pyruvate inhibits PDH Kinase and this stimulates the PDH complex.
2.High NADH and ATP also directly inhibits PDH complex. It also indirectly inhibits it via activating PDH kinase.
- PDH phosphatase. : it takes away phosphate on E1 of the PDH complex and this stimulates it.
Calcium stimulates PDH phosphatase.
Apart from calcium, insulin also stimulates PDH phosphatase
Magnesium (Mg²⁺) is an essential cofactor for the pyruvate dehydrogenase (PDH) complex, which catalyzes the conversion of pyruvate to acetyl-CoA. Here’s how magnesium is involved:
Role of Magnesium in the PDH Complex:
1. Required for Enzyme Activity:
• Magnesium is necessary for the proper functioning of pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase, which regulate the PDH complex through phosphorylation and dephosphorylation.
• These regulatory enzymes use Mg²⁺-ATP complexes as a substrate.
2. Stabilization of Thiamine Pyrophosphate (TPP):
• TPP, a coenzyme derived from vitamin B1 (thiamine), requires Mg²⁺ for its binding to the PDH complex.
• Without magnesium, TPP cannot function effectively, and the decarboxylation of pyruvate is impaired.
3. Indirect Effect on Energy Metabolism:
• If Mg²⁺ is deficient, PDH activity drops, leading to pyruvate accumulation, lactic acidosis, and impaired entry of carbon into the TCA cycle.
Clinical Link:
• Magnesium deficiency can mimic signs of thiamine deficiency because both impair PDH activity.
• This is especially critical in alcoholic patients, where both thiamine and magnesium may be low.
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How many electrons does acetyl coA feed into the Krebs?
How is ethanol converted to acetyl coA
Krebs is the hub of cellular metabolism.
8 and it feeds 4 pairs of electrons. So note the diff. If they say pairs, it’s 4. If just electrons, it’s 8.
Great question! Let’s break it down clearly:
“Acetyl-CoA feeds 4 pairs of electrons” — What does that mean?
1 Acetyl-CoA enters the TCA (Krebs) cycle, and through a series of reactions, it leads to the transfer of 4 pairs of electrons (8 electrons total) to electron carriers.
Here’s how:
From Dehydrogenase Reactions in the Cycle:
1. Isocitrate → α-ketoglutarate
• Enzyme: Isocitrate dehydrogenase
• Produces 1 NADH → 1 electron pair
2. α-Ketoglutarate → Succinyl-CoA
• Enzyme: α-ketoglutarate dehydrogenase
• Produces 1 NADH → 1 electron pair
3. Malate → Oxaloacetate
• Enzyme: Malate dehydrogenase
• Produces 1 NADH → 1 electron pair
4. Succinate → Fumarate
• Enzyme: Succinate dehydrogenase (Complex II)
• Produces 1 FADH₂ → 1 electron pair
Summary:
Step Electron Carrier Electron Pairs
Isocitrate → α-KG NADH 1
α-KG → Succinyl-CoA NADH 1
Malate → Oxaloacetate NADH 1
Succinate → Fumarate FADH₂ 1
Total — 4 pairs
These 4 electron pairs (3 NADH + 1 FADH₂) go to the electron transport chain (ETC), driving ATP production.
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The conversion of ethanol to acetyl-CoA occurs in the liver and involves three main steps, each catalyzed by a specific enzyme:
- Ethanol → Acetaldehyde
Enzyme: Alcohol dehydrogenase (ADH)
Cofactor: NAD⁺ → NADH
Location: Cytosol
Reaction:
Ethanol + NAD⁺ → Acetaldehyde + NADH + H⁺
- Acetaldehyde → Acetate
Enzyme: Aldehyde dehydrogenase (ALDH)
Cofactor: NAD⁺ → NADH
Location: Mainly mitochondrial
Reaction:
Acetaldehyde + NAD⁺ → Acetate + NADH + H⁺
- Acetate → Acetyl-CoA
Enzyme: Acetyl-CoA synthetase (aka acetate thiokinase)
Cofactor: ATP → AMP + PPi
Location: Mitochondria or cytosol depending on tissue
Reaction:
Acetate + CoA + ATP → Acetyl-CoA + AMP + PPi
Key Notes:
• This pathway generates 2 NADH, which go to the ETC.
• Excess NADH can lead to lactic acidosis and fatty liver.
• Acetyl-CoA can’t be converted back to glucose—so ethanol is not gluconeogenic.
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How does arsenate and mercury poisoning affect Tca?
Arsenic/mercury poisoning
Arsenic either in the form of arsenate or arsenite has been used as a poison because it can bind to sulfhydryl compounds in lipoic acids and cysteine residues.
It can also inhibit glyceraldehyde-3-phosphate dehydrogenase in glycolysis affecting anaerobic respiration.
The inactivation of lipoamide
containing
enzymes
especially
pyruvate
dehydrogenase and a-ketoglutarate dehydrogenase complexes brings aerobic respiration to a halt and lead to nervous system pathologies.
Arsenic is however more toxic to microorganisms than humans and was once used as antibiotics and overlooking the side effects.
Symptoms include headache, diarrhoea, vomiting, convulsions etc. Organs seriously affected are kidneys and lungs and fatal exposures lead to coma and death.
Since arsenic can bind to the sulfhydryl group it binds to the cysteine residues of keratin at exposure time and forensics can estimate the time of initial intake.
The low doses found in water bodies around the world are a public health hazard since it has been linked to cancer.
State the five main coenzymes in the Krebs cycle
What are cataplerotic reaction?
Replenishing TCA cycle intermediates
If the intermediates are drawn off for biosynthesis then they need to be replenished when the energy needs of the cells rises.
For example if OAA is used for amino acids, the TCA cycle will operate at a reduced rate till enough OAA is available for acetyl CoA reaction.
Mammals lack enzymes that can convert acetyl CoA into any TCA intermediate without oxaloacetate.
Just like acetyl CoA, oxaloacetate can also be formed from pyruvate in a carboxylation reaction catalyzed by pyruvate carboxylase, which requires biotin.
Pyruvate + CO2 + ATP + H20 + GDP -
• Oxaloacetate + ADP + Pi +
5.
The enzyme is active only in the presence of acetyl CoA which signifies the need for more oxaloacetate and is an example of an anaplerotic (fill up) reaction.
main coenzymes are NAD+, FAD, CoASH, TPP and lipoamide.
Even though FAD accept two electrons, it can accept the electrons in sequential order-one at a time. Thus single electrons can be transferred from two different carbon atoms. Reactions that result in the formation of double bonds have FAD involvement.
3.FAD is also bound to the enzyme and accepts electrons from substrates that is also bound to the same enzyme and donates these electrons without leaving the enzyme.
4.NAD+ accepts two electrons from the same carbon atom or atoms binding to a carbon atom when bound to any dehydrogenase. Unlike FAD, NAD+ can detach from that dehydrogenase and donate the electrons when bound to a different dehydrogenase.
5.The free movement of NAD+ enables it play a regulatory role in balancing energy metabolism. By binding to different dehydrogenases it can inhibit their actions hence NADH/NAD+ ratios regulating the TCA cycle rate
CoASH participates in reactions that form a high energy thioester bond between the S of CoASH and an acyl group. It is obtained from its vitamin precursor pantothenate.
2.The high energy from succinyl CoA is used to activate an enzyme bound phosphate, that is transferred to GDP to form GTP. In acetyl CoA, the energy is used in the synthesis of citrate thus keeping the TCA cycle going in the forward direction.
3.Thiamine pyrophosphate is synthesized from thiamine and its function is the cleavage of carbon-carbon bond next to a keto group.
4.Lipoate is found in the dehydrogenase complexes and attached to the transacetylase potion of the enzyme complex.
5.Lipoamides contain the disulphide group which becomes reduced when it accepts electrons and in the case of the TCA cycle can accept the acyl group being delivered by TPP and transfer it to the site containing the CoASH
The TCA cycle in addition to its degradative function also provides intermediates for biosynthesis. Reactions that drain the TCA of its intermediates are called cataplerotic (emptying) reactions.
Great — here are key TCA intermediates that are used in cataplerotic (emptying) reactions, meaning they are pulled out of the cycle for biosynthesis:
- Citrate
• Used to make: Fatty acids and cholesterol or sterols
• How: Citrate is transported out of mitochondria → converted back to acetyl-CoA in the cytosol - α-Ketoglutarate
• Used to make: Glutamate, which can become other amino acids or neurotransmitters
• Also involved in: Purine synthesis - Succinyl-CoA
• Used to make: Heme ,porphyrins ,chlorophyll
(important for hemoglobin and cytochromes) - Malate
• Can be shuttled to the cytosol to form: Oxaloacetate
• Oxaloacetate is then used for: Gluconeogenesis - Oxaloacetate
• Used to make: Aspartate, which contributes to urea cycle, pyrimidine synthesis, and other amino acids
These cataplerotic reactions are essential for biosynthesis, but because they deplete the TCA intermediates, anaplerotic reactions must replenish them to keep the cycle going. Would you like examples of those too?
Deficiency of the TCA cycle enzymes
There are very few genetic diseases affecting the TCA cycle enzymes an indication of the essential nature of the cycle.
Diseases if any are very serious and most of them affect the nervous system.
Those with pyruvate dehydrogenase deficiency exhibit elevated levels of lactate, pyruvate and alanine. They exhibit neurological defects which normally result in death.
With fumarase deficiency, there is neurological impairment and encephalomyopathy. The urine contains high amounts of fumarate succinate, citrate amongst others.
Great question — let’s break it down simply:
Can glucose become fat?
Yes.
When you eat more glucose (carbs) than your body needs for energy:
• It is converted to pyruvate, then to acetyl-CoA.
• If energy is already sufficient, acetyl-CoA doesn’t go through the TCA cycle.
• Instead, it’s used to make fatty acids (lipogenesis), which are stored as fat (triglycerides).
Glucose → pyruvate → acetyl-CoA → fatty acids → fat
Can fat become glucose?
No, not in animals (including humans).
Why?
• When fat is broken down, you get acetyl-CoA.
• But acetyl-CoA cannot be converted back into pyruvate or glucose.
• This is because the pyruvate → acetyl-CoA step is irreversible.
• Also, in the TCA cycle, the 2 carbons in acetyl-CoA are lost as CO₂, so nothing is left to turn into glucose.
So:
• Glucose can become fat.
• Fat cannot become glucose.
Let me know if you’d like a diagram or a memory trick for this.
1.A patient with thiamine deficiency exhibited fatigue and muscle cramps due to accumulation of metabolic acids. Which of the following will accumulate when there is thiamine deficiency
a.Succinic acid
b.Oxaloacetic acid
c.Citric acid
d.Pyruvic acid
- All the following TCA cycle intermediates may be added or removed by other pathways except
a.citrate
b.oxaloacetate
c.isocitrate
d.α-ketoglutarate
When necessary pyruvate is converted to oxaloacetate by pyruvate carboxylase whose activity is stimulated by an increased concentration of
a.citrate
b.pyruvate
c.Isocitrate
d.Acetyl CoA
A person suffering from Friedreich’s ataxia has problems converting pyruvate to acetyl CoA. Such a person may be lacking the enzyme
a.Succinate dehydrogenase
b.Pyruvate dehydrogenase kinase
c.Dihydrolipoyl dehydrogenase
d.Citrate synthase
child accidentally ingests fluoroacetate, which is rat poison. Which of the following substrates does this poison reacts with?
A.oxaloacetate
B.acetoacetate
C.isocitrate
D.succinate
Which of the following vitamins is required for the synthesis of one of the cofactors in the pyruvate dehydrogenase complex reaction?
A.biotin
B.pantothenate
C.pyridoxine
D.ascorbic acid
Substrate-level phosphorylation differs from oxidative phosphorylation in that
A.oxidative phosphorylation only occurs in the cytosol
B.substrate-level phosphorylation involves the transfer of electrons
C.oxidative phosphorylation involves the transfer of electrons
D.substrate-level phosphorylation only occurs in the cytosol
1.D
2.C
3.d
4.c
5.a-The correct answer is: A. oxaloacetate
Explanation:
Fluoroacetate is a potent metabolic poison. In the body, it is converted to fluoroacetyl-CoA, which combines with oxaloacetate to form fluorocitrate via the enzyme citrate synthase. Fluorocitrate then inhibits aconitase, an enzyme in the TCA cycle, which disrupts energy production.
So, the poison reacts with oxaloacetate to form the toxic compound fluorocitrate.
6.b
7.c
Citric acid is both catabolic and anabolic
Glycolysis produces more ATP than citric acid cycle
Why?
2 pyruvate: 2 atp in citric acid gross
Glycolysis: 4 gross atp
So glycolysis is more if you dont focus on the investment but focus on the gross
always focus on the gross until stated otherwise
Why is ATP used over the other energy currencies like gtp, etc
Why is citric acid more of anabolic than catabolic or so
How different will arsenate in its inhibition compared to fluoroscetat
When NADH is more oxidized you get more energy
If you oook at the l reducing equivalents from both , citric will be more
Great questions! Here’s a breakdown of each one:
Answer:
ATP (adenosine triphosphate) is the primary energy currency of the cell because of several reasons:
- Universality: ATP is used by virtually all forms of life. This makes it a reliable, universal molecule for energy transfer.
- Efficient energy release: Hydrolysis of ATP releases a manageable amount of energy (\~7.3 kcal/mol), ideal for cellular reactions without being wasteful or overly disruptive.
- Stability and availability: ATP is more stable and abundant in cells compared to GTP, UTP, or CTP.
- Versatility: ATP powers not only metabolic reactions but also mechanical work (muscle contraction), transport, and signaling (like kinases).
> However, GTP, UTP, and CTP are still used in specific processes:
- GTP in protein synthesis and G-protein signaling
- UTP in glycogen synthesis
- CTP in lipid synthesis
Answer:
The citric acid cycle (TCA cycle) is amphibolic — it serves both catabolic and anabolic purposes.
- Catabolic role: It oxidizes acetyl-CoA from carbohydrates, fats, and proteins to CO₂, generating NADH and FADH₂ for ATP production.
-
Anabolic role: It provides precursors for biosynthesis:
- Citrate → fatty acids
- α-ketoglutarate → amino acids
- Succinyl-CoA → heme synthesis
- Oxaloacetate → gluconeogenesis, amino acids
> Because of these biosynthetic offshoots, the TCA cycle is often considered more anabolic in its integration with overall metabolism.
Answer:
Summary:
- Fluoroacetate = TCA cycle inhibitor (mitochondrial poison)
- Arsenate = Glycolysis disruptor (energy uncoupler)
Let me know if you want visual diagrams or analogies to help explain these in a presentation or notes!
Excellent observation — and you’re absolutely right to bring this up, because arsenic compounds can inhibit enzymes in different ways, depending on the form of arsenic involved. Here’s the clarification:
- Mechanism: Arsenate mimics inorganic phosphate (Pi) in reactions like glycolysis.
- Inhibition: It substitutes for Pi in the glyceraldehyde-3-phosphate dehydrogenase step.
- Effect: Forms an unstable arseno-analog of 1,3-bisphosphoglycerate, which hydrolyzes spontaneously — so no ATP is generated, leading to energy deficiency.
-
Mechanism: Arsenite binds to lipoic acid, a cofactor required by:
- Pyruvate dehydrogenase (PDH)
- α-Ketoglutarate dehydrogenase (in the TCA cycle)
- Effect: Inhibits these key dehydrogenase complexes, blocking entry of carbohydrates into the TCA cycle.
- Arsenate inhibits ATP production in glycolysis by acting as a phosphate analog.
- Arsenite inhibits dehydrogenases like PDH and α-KGDH by binding to lipoic acid.
| Toxin | Target | Main Effect |
| —————– | —————————– | —————————————————————– |
| Fluoroacetate | Aconitase (via fluorocitrate) | Blocks TCA cycle → halts respiration |
| Arsenite | Lipoic acid (PDH, α-KGDH) | Blocks conversion of pyruvate and α-KG to acetyl-CoA/succinyl-CoA |
| Arsenate | Glycolysis (G3PDH step) | ATP depletion due to uncoupled glycolysis |
Let me know if you’d like this as a table or visual for presentation use!
Fluoroacetate | Arsenate |
| ————————————————————————————————- | ——————————————————————————————————— |
| Mimics acetate and forms fluoroacetyl-CoA | Mimics phosphate (Pi) and interferes in ATP-generating steps |
| Combines with oxaloacetate → fluorocitrate, which inhibits aconitase in the TCA cycle | Substitutes for Pi in glycolysis, especially at glyceraldehyde-3-phosphate dehydrogenase (G3PDH) step |
| Blocks TCA cycle → halts energy production at the mitochondrial level | Causes uncoupling of glycolysis → glucose breakdown without ATP gain |
| Leads to toxic accumulation of citrate and halts respiration | Leads to inefficient energy yield and potential cell death |
ETC occurs in the inner mitochondrial membrane
How does ETc occur? Using the reducing agents from Krebs cycle
Why does FADH2 produce less ATP than NaDH
NADH dehydrogenase or complex I:
NADH is oxidized to NAD+
FMN(flavin mononucleotide) is reduced to FMNH2 by taking the Hydride ion(H plus 2 electrons) . FMNH₂ then passes the electrons through a chain of iron-sulfur (Fe-S) clusters and the electrons get to coenzyme Q(ubiquinone).
Coenzyme Q when it takes these electrons becomes or is reduced to coenzyme QH2(Ubiquinol).
The coenzyme Q isn’t made up of protein.
So the passage of the 2 electrons from NADH to FMN to coenzyme Q, produces energy that causes a change in the conformational shape of the pores in the membrane of complex I. This change in shape opens the proton channels or pores and this pumps 4 protons (per the 2 electrons that were transferred )into the intermembrane space.
Succinate dehydrogenase or complex II:
FADH2 comes in and drops of the electrons via oxidation to get FAD+. FMN takes the electrons released by FADH2 and becomes FMNH2
The electrons are passed through iron sulfur chains to get to coenzyme Q to reduce it to coenzymeQH2.
This complex II doesn’t have the pore to pump out the electrons as protons and it also doesn’t have enough energy to do so.
Complex I = High-energy electrons → pumps 4 H⁺
• Complex II = Lower-energy electrons → no proton pumping
This is why FADH₂ produces less ATP than NADH: it bypasses Complex I and contributes less to the proton gradient needed for ATP synthesis.
- Complex III or coenzyme Q : cytochrome b reductase or cytochrome bc1 complex.
So coenzyme QH2 takes the electrons it gained from complex 1 and takes what it gained separately from complex 2 and sends all the 4 electrons to complex 3.
So when It sends it to specifically cytochrome b which has an iron molecule attached to it, coenzymeQH2 goes back to being coenzyme Q.
The iron accepts the electrons and gets reduced from FE3+ to FE2+
Complex III has a pore that it can use to pump out protons so the same thing that happened to complex I is occurring in complex III.
Note that: Exactly! Cytochromes are proteins that contain heme groups—the same kind of porphyrin ring structure found in hemoglobin. These heme groups have an iron atom at the center that can accept and donate electrons, allowing cytochromes to act as electron carriers in the electron transport chain.
So, cytochromes are basically heme-containing proteins specialized for electron transfer.
- The iron in cytochrome b from complex III sends its electrons to cytochrome c1 which is in the complex III and that cytochrome c1 sends it to cytochrome C which is a mobile electron carrier just like coenzyme Q.
Step 4: complex IV or cytochrome oxidase. It contains cytochrome A or cytochrome a3
Note that: Each time a cytochrome gives up an electron, its iron atom is oxidized, meaning:
•Fe²⁺ (reduced) → Fe³⁺ (oxidized). So:•When a cytochrome receives an electron: it’s original Fe³⁺ → becomes Fe²⁺
•When it passes the electron to the next carrier or complex, it moves from Fe²⁺ → to its original Fe³⁺
This reversible switch is what allows iron in the ETC to act as a conveyor belt for electrons without being consumed.
Oxygen is the last electron acceptor after complex IV. So it’s half of oxygen that combines with 2 protons (2H) from the mitochondria to form water.
The 2 protons released by complex IV get pumped out by its pore into the Inter membrane space
Note: You’re very close — just a small correction in your flow:
Correct flow explained simply:
1. Coenzyme Q (ubiquinone) picks up 2 electrons from Complex I or 2 electrons from Complex II, not both at once.
• NADH → Complex I → CoQ → CoQH₂ (2 e⁻)
• FADH₂ → Complex II → CoQ → CoQH₂ (2 e⁻)
2. CoQH₂ delivers its 2 electrons to Complex III.
• Complex III splits the 2 electrons and sends them one at a time to 2 cytochrome c molecules.
3. Each cytochrome c carries 1 electron to Complex IV.
• So from 1 CoQH₂, Complex IV receives 2 electrons via 2 cytochrome c molecules.
4. To reduce 1 oxygen molecule (O₂) to 2 water molecules (H₂O), Complex IV needs 4 electrons.
• So 2 CoQH₂ molecules (from either Complex I or II) must send electrons.
• This gives 4 electrons, which are delivered by 4 cytochrome c molecules.
Cuz cytochrome c can only hold on to one electron at a time and QH2 can only hold on to two at a time. So QH2 will go two times to get your 4 electrons and cytochrome c will go four times to give the 4 electrons to complex IV to reduce oxygen to water.
So putting it together:
• 2 NADH molecules (or NADH + FADH₂) each send electrons via their respective complexes.
• CoQ gets 2 electrons each time and forms CoQH₂.
• Each CoQH₂ delivers 2 electrons to Complex III.
• Complex III sends them (1 at a time) to cytochrome c.
• 4 cytochrome c → deliver 4 electrons to Complex IV → reduce 1 O₂ + 4 H⁺ → 2 H₂O.
Summary:
• CoQ doesn’t send electrons to Complex II.
• Complex II is a donor, not a receiver.
• Complex I and II donate electrons to CoQ.
• CoQ sends to Complex III, which sends via cytochrome c to Complex IV.
• 4 electrons needed at Complex IV = 2 rounds of CoQH₂ donation.
Would you like a diagram or card question to help you remember this better?
Let me break it down more simply:
What happens at Complex IV (cytochrome c oxidase)?
Step 1: Electrons arrive
• 4 cytochrome c molecules each bring 1 electron.
• Total = 4 electrons.
Step 2: These electrons reduce oxygen
• 1 molecule of O₂ (oxygen) needs 4 electrons to become 2 molecules of water (H₂O).
Step 3: To make water, protons are needed
• 4 protons from the mitochondrial matrix combine with the oxygen and electrons to form water.
• (So these protons are used, not pumped).
Step 4: Protons are also pumped out
• While making water, 2 other protons are actively pumped from the matrix into the intermembrane space to help build the proton gradient.
Summary:
• 4 electrons come from cytochrome c.
• 4 protons are used to make water.
• 2 protons are pumped to the intermembrane space.
Let me know if you want a drawing or flashcard version!
Electrons transferred and ôtons pumped at each complex
Perfect! Here’s a step-by-step breakdown of the electron transport chain (ETC), clearly showing:
• Number of electrons (e⁻) transferred
• Number of protons (H⁺) pumped
Step 1: Complex I (NADH Dehydrogenase)
• Input: 1 NADH → donates 2 e⁻
• Process:
• Electrons pass from NADH → FMN → Fe-S clusters → CoQ
• CoQ becomes CoQH₂
• Protons pumped: 4 H⁺ into the intermembrane space
• Electrons moved: 2 e⁻ to CoQ
Step 2: Complex II (Succinate Dehydrogenase)
• Input: 1 FADH₂ → donates 2 e⁻
• Process:
• Electrons go from FADH₂ → Fe-S → CoQ
• CoQ becomes CoQH₂
• Protons pumped: 0 H⁺
• Electrons moved: 2 e⁻ to CoQ
Step 3: Coenzyme Q (Ubiquinone)
• Accepts 2 e⁻ from either Complex I or II → becomes CoQH₂
• Transfers 2 e⁻ to Complex III
• These are passed one at a time to 2 cytochrome c molecules
Step 4: Complex III (Cytochrome bc1 / Cytochrome b-c1 complex)
• Input: 1 CoQH₂ → donates 2 e⁻
• Process:
• 2 e⁻ → 2 cytochrome c molecules (each carries 1 e⁻)
• Protons pumped: 4 H⁺
• 2 H⁺ from CoQH₂ released
• 2 H⁺ pumped from the matrix
• Electrons moved: 2 e⁻ to 2 cytochrome c
Step 5: Complex IV (Cytochrome c oxidase)
• Input: 4 cytochrome c molecules → deliver 1 e⁻ each → total = 4 e⁻
• Process:
• 4 e⁻ + 4 H⁺ + 1 O₂ → 2 H₂O
• Protons pumped: 2 H⁺
• Electrons used: 4 e⁻
Overall Summary (Per 2 NADH or 2 FADH₂ → 4 e⁻):
Complex Electrons moved Protons pumped
Complex I 2 4
Complex II 2 0
CoQ → III 2 0
Complex III 2 4
Complex IV 4 2
Let me know if you’d like a visual diagram or flashcards to reinforce this!
Here are the flashcard questions first (electron transport chain, focusing on electrons moved and protons pumped):
1. What happens to NADH at Complex I in terms of electron transfer and proton pumping?
2. What is the role of FMN in Complex I, and how does it contribute to the electron transport chain?
3. How many electrons does Complex I transfer to Coenzyme Q, and how many protons does it pump?
4. What is the role of Complex II in electron transport and does it pump protons?
5. How does Coenzyme Q (Q or QH2) transport electrons between Complex I/II and Complex III?
6. How many electrons does Coenzyme QH2 deliver to Complex III, and how many protons does Complex III pump?
7. What is the role of cytochrome c in electron transport, and how many electrons can it carry at once?
8. How many cytochrome c molecules are needed to transfer 4 electrons to Complex IV?
9. How many electrons does Complex IV use to reduce one molecule of oxygen to water, and how many protons does it pump and use internally?
10. In total, how many protons are pumped across the inner mitochondrial membrane for every pair of electrons from NADH?
Let me know when you’re ready for the answers.
Note that transition from high energy to low energy releases protons. High energy when they get electrons and low energy when they throw away the electrons to the next.
Here are the answers to the flashcard questions above:
1. What happens to NADH at Complex I in terms of electron transfer and proton pumping? NADH is oxidized to NAD⁺, donating 2 electrons. Complex I pumps 4 protons into the intermembrane space. 2. What is the role of FMN in Complex I, and how does it contribute to the electron transport chain? FMN accepts the hydride ion (2 electrons + 1 proton) from NADH, forming FMNH₂. It then passes the electrons down the chain to iron-sulfur (Fe-S) clusters. 3. How many electrons does Complex I transfer to Coenzyme Q, and how many protons does it pump? Complex I transfers 2 electrons to Coenzyme Q (reducing it to QH₂) and pumps 4 protons. 4. What is the role of Complex II in electron transport and does it pump protons? Complex II receives 2 electrons from FADH₂ and transfers them to Coenzyme Q (forming QH₂), but does not pump protons. 5. How does Coenzyme Q (Q or QH₂) transport electrons between Complex I/II and Complex III? QH₂ carries 2 electrons and moves freely in the membrane, delivering electrons from Complex I or II to Complex III. 6. How many electrons does Coenzyme QH₂ deliver to Complex III, and how many protons does Complex III pump? QH₂ delivers 2 electrons to Complex III, and Complex III pumps 4 protons into the intermembrane space (2 per QH₂, but it happens twice per NADH/FADH₂ to fully reduce oxygen). 7. What is the role of cytochrome c in electron transport, and how many electrons can it carry at once? Cytochrome c shuttles 1 electron at a time from Complex III to Complex IV. 8. How many cytochrome c molecules are needed to transfer 4 electrons to Complex IV? 4 cytochrome c molecules are needed to transfer 4 electrons to Complex IV. 9. How many electrons does Complex IV use to reduce one molecule of oxygen to water, and how many protons does it pump and use internally? Complex IV uses 4 electrons to reduce O₂ to 2H₂O. It pumps 2 protons and uses 4 protons from the matrix to form the water. 10. In total, how many protons are pumped across the inner mitochondrial membrane for every pair of electrons from NADH? 10 protons: 4 from Complex I, 4 from Complex III, and 2 from Complex IV.
Let me know if you’d like these in flashcard format (e.g., one per slide or image), or if you want a quiz version!
Note that Krebs produces 6NADH and 2 FaDH2.
Each NADH will produce 2 electrons and pump 4 protons.
each NADH results in:
• 10 protons pumped in total:
• 4 (Complex I)
• 4 (Complex III)
• 2 (Complex IV)
• This proton gradient drives the synthesis of ~2.5 ATP
per FADH₂:
• 2 electrons transferred
• Total of 6 protons pumped:
• 0 at Complex II
• 4 at Complex III
• 2 at Complex IV
Complex I isn’t part cuz fadh2 starts from complex II
ATP Yield:
• The proton gradient from FADH₂ (6 protons) drives synthesis of about 1.5 ATP
Electrons donated by nadh2 in total is 2 and sane for FADH2
Just that those 2 electrons are transferred saa and per each transfer, protons are pumped out but the same number of 2 electrons remains the same.
So To get the 4 electrons needed to fully reduce one O₂ molecule at Complex IV, you need:
• 2 NADH molecules (or a mix of NADH + FADH₂)
Q goes back multiple times, each time carrying 2 electrons from a new NADH or FADH₂.
The 2NADH (1NADH per pyruvate) from pyruvate dehydrogenase complex can enter freely into the mitochondria cuz the preparatory phase occurs in the mitochondria
But the NADH from glycolysis can’t enter the mitochondria just like that cuz glycolysis occurs in the cytosol. hasn’t been accounted for yet.
So glucose makes 10nadh in all(remember 1 glucose gives 2 pyruvate) :
2 from glycolysis 2 from pyruvate dehydrogenase complex 6 from Krebs cycle.
the NADH from glycolysis (in the cytosol) needs to enter the mitochondria to participate in the electron transport chain (ETC), but it can’t cross the inner mitochondrial membrane directly. So it uses a shuttle system to get its electrons inside.
Explain how this process occurs
Revise your glycolysis and things cuz their enzymes are used a lot
There are two main shuttles used:
1. Malate aspartate shuttle(used in heart, liver, kidney):
Most efficient, no loss of ATP.
The NADH from glycolysis is in the cytosol and
Some Oxaloacetate in the cytosol uses the NADH to form Malate so the NADH is oxidized to nad+
All this is done by Malate dehydrogenase. So this enzyme picks the electrons and drops them on Oxaloacetate to make it Malate making NADH oxidized to nad+.
Oaa can’t cross the cytosol to get into the mitochondria but Malate can.
Malate goes in as aspartate is coming out via the Malate aspartate shuttle.
Malate goes in and Malate dehydrogenase plucks the electrons from Malate and gives it back to nad to form nadh. This nadh enters complex 1 and goes through the etc.
Malate without its electrons goes back to being Oxaloacetate.
This Oxaloacetate in the mitochondria reacts with glutamate to form aspartate and alpha ketoglutarate which move out of the mitochondria and into the cytosol. The aspartate gets out and combines with alpha ketoglutarate in the cytosol to form Oxaloacetate and glutamate and everything starts all over again.
- Glycerol-3-Phosphate Shuttle (used in brain, skeletal muscle)
So dihydroxyacetone phosphate picks up electrons from the NaDH in the cytosol and when this happens, NaD+ is produced and glycerol 3 phosphate is produced.
This G3P gets into the mitochondria and glycerol 3-phosphate dehydrogenase takes the electrons from G3P and gives it to FAD+ to form FADH2. When this happens, G3P goes back to being dihydroxyacetone phosphate.
Then the FADH2 enters ETC via complex II.
Because electrons enter via Complex II, which doesn’t pump protons, the ATP yield is slightly lower than NADH entering via Complex I.
- Third way is by reducing fatty acyl coA to enoyl coA via acyl coA dehydrogenase. FAD is converted to FADH2 by electrons taken from fatty acyl coA. This third way only occurs when there is beta oxidation.
Last part of electron transport chain after complex IV.
Explain how complex V or ATP synthase occurs.
Chemiosmosis is the process where protons (H⁺) flow down their concentration gradient through ATP synthase, leading to the production of ATP.
Explain oxidative phosphorylation(it’s different from substrate phosphorylation)
So from complex I to complex IV, a concentration gradient was established by the pumping of plenty protons into the inter membrane space.
The concentration gradient established will be moving from high to low so from the inter membrane space to the matrix.
ATP synthase is like a turbine.
ATP synthase has two pores. One opens for the protons in the inter membrane space to get into the matrix via the A protein pore and get out through the other A protein pore to go into the matrix. Cuz there are two pores one on each side.
Protein motor force generated and atp synthase absorbs some of the energy as potential energy as the protons move from high to low
The synthase uses the energy to put ADp and inorganic phosphate together. This ADP and inorganic phosphate are on the beta catalytic sub unit on the knob.
How does 2,4DNP cause problems in ATP generation
There’s a drug (2,4-Dinitrophenol (2,4-DNP) is a chemical uncoupler of oxidative phosphorylation) that creates a hydrophobic pore in the mitochondria to make protons pass through that mmom but no atp will be produced. So an alternative route.
So it uncouples the ETC and ATp synthase that are supposed to work together to produce ATP from the protons generated.
2,4-Dinitrophenol (2,4-DNP) is a chemical uncoupler of oxidative phosphorylation.
What it does:
• It disrupts the proton gradient across the inner mitochondrial membrane.
• It makes the membrane leaky to protons, so H⁺ ions bypass ATP synthase and re-enter the mitochondrial matrix directly.
• Energy from electron transport is released as heat instead of being used to synthesize ATP.
Effect on the cell:
• ETC still runs (electrons move, oxygen is consumed, and protons are pumped out).
• But no ATP is produced because the proton motive force is lost.
• Increased oxygen consumption (ETC works harder to compensate).
• Heat is generated → can lead to hyperthermia and death in overdose.
Used for?
• Previously used as a weight-loss drug in the 1930s (dangerous).
• Now used in research to study mitochondria and metabolism.
Would you like a visual or flashcard format for this?
How does cyanide and carbon monoxide inhibit ETC?
How does it cause histotoxic hypoxia?
Prevents transfer of electrons to the oxygen
Cyanide inhibits the electron transport chain (ETC) by binding to Complex IV (cytochrome c oxidase).
Mechanism of Inhibition:
• Cyanide (CN⁻) binds tightly to the iron (Fe³⁺) in the heme group of cytochrome a₃ (part of Complex IV).
• This prevents oxygen (O₂) from binding.
• Result: Electrons cannot be transferred to oxygen, so oxygen can’t be reduced to water.
Consequences:
• Electron flow halts → ETC stops working.
• No proton gradient → ATP synthase can’t produce ATP.
• Cellular respiration stops, despite the presence of glucose and oxygen.
• Energy crisis in cells → especially in the brain and heart.
• Can lead to cell death and fatal hypoxia (even when oxygen is available — called histotoxic hypoxia).
Oxygen is available in the blood and tissues.
• But cells can’t use it because cyanide blocks Complex IV of the ETC.
• So oxygen can’t accept electrons → no water is formed → cellular respiration stops.
• Tissues are starved of usable oxygen, even though it’s physically present.
Great question.
Cyanide poisoning doesn’t stop you from breathing — your lungs still work and you’re still inhaling oxygen.
The problem is what happens after the oxygen gets into your blood:
• Cyanide binds to cytochrome c oxidase (Complex IV) in the electron transport chain.
• This prevents oxygen from accepting electrons at the end of the chain.
• So cells can’t use the oxygen for ATP production — even though it’s in the blood and tissues.
• This leads to histotoxic hypoxia (tissues are starved of usable oxygen).
So what happens when cells can’t use oxygen?
• Cells switch to anaerobic respiration → lactic acid builds up.
• ATP production plummets → organs start to fail.
• Brain and heart are affected first → can lead to death despite normal breathing.
Summary:
You can breathe, oxygen is in your body, but your cells can’t use it because cyanide blocks the ETC. So breathing doesn’t help — that’s why it’s so deadly.
Oxygen Pathway (Normally)
• You breathe in oxygen.
• Oxygen diffuses into your blood in the lungs.
• In the blood, it binds to hemoglobin in red blood cells (RBCs).
• RBCs transport oxygen to tissues.
• Oxygen is released from hemoglobin and diffuses into cells.
• Inside cells, oxygen goes to the mitochondria, where it acts as the final electron acceptor in the electron transport chain (ETC), allowing ATP production.
- In Cyanide Poisoning
• All the above steps still happen.
• Oxygen enters the lungs → binds to hemoglobin → reaches cells.
• BUT when oxygen gets to mitochondria, cyanide has blocked Complex IV (cytochrome c oxidase).
• Oxygen can’t accept electrons, so it can’t be used for energy production. - What Happens to the Oxygen in RBCs?
• RBCs still carry oxygen.
• Oxygen is still released into tissues.
• But the mitochondria reject it because Complex IV is blocked.
• So oxygen builds up in tissues — blood may even remain bright red due to high oxygen.
Great follow-up! Let’s compare carbon monoxide (CO) to cyanide in how they affect oxygen and the electron transport chain (ETC).
- Carbon Monoxide (CO): What does it do?
CO causes hypoxia, but in a different way than cyanide.
a. Binds to Hemoglobin (Hb)
• CO binds to hemoglobin with 200–250x greater affinity than oxygen.
• This means CO displaces oxygen from hemoglobin.
• So, less oxygen is transported in the blood.
b. Reduces Oxygen Delivery to Tissues
• Since Hb is mostly bound to CO, very little O₂ is delivered to tissues.
• This causes hypoxic hypoxia — oxygen isn’t even reaching cells.
c. Also Affects Mitochondria (Secondary Effect)
• CO can bind to Complex IV (cytochrome c oxidase) in mitochondria too (like cyanide), though less potently.
• This blocks ETC, making oxygen useless even if it gets to the cell.
- Comparison with Cyanide
Feature Carbon Monoxide Cyanide
Primary Action Blocks oxygen carrying by hemoglobin Blocks oxygen use in mitochondria
Oxygen in RBCs? Yes, but very little (Hb mostly bound to CO) Yes, normal or high (not the problem)
Oxygen in tissues? Low (not delivered) Normal/high (but not used)
Mitochondria use oxygen? No (because not enough O₂) No (Complex IV blocked)
Type of hypoxia Hypoxic hypoxia Histotoxic hypoxia
Summary:
• CO prevents oxygen from reaching the cells.
• Cyanide prevents cells from using the oxygen.
• Both result in severe hypoxia, but by different mechanisms.
Let me know if you’d like a simple memory trick for the difference!
Brown adipose tissue has a lot of mitochondria in it that’s why it’s browns and mitochondria has a lot of iron in it which gives it its brown color
It produced a lot of heat for babies via a pathway like what the 2,4DNp does but it does it specifically only in brown adipose tissue.
It produces a molecule called thermogenin which creates like a pore or channel in the inner mitochondria membrane .
The normal is : Protons re-enter via ATP synthase and the
Energy is used to make ATP
But in thermogenin, Protons bypass ATP synthase and Energy is released as heat.
• So, instead of making ATP, the proton gradient is dissipated as heat.
• This is exactly what 2,4-DNP does, but dangerously and system-wide.
• Thermogenin is safe and controlled, and only active in brown fat.
Brown fat burns fuel to generate heat (not ATP) through thermogenin, a natural mitochondrial uncoupler. It’s a baby’s built-in heater.
Little atp is produced so you’ll get a lot of heat.
Because most of the proton gradient bypasses ATP synthase (due to thermogenin or uncouplers like 2,4-DNP), very little ATP is produced.
Instead, the energy from the electrons in the electron transport chain is released as heat, not stored as ATP.
Oligomycin is an antibiotic that inhibits ATP synthase (Complex V) by blocking its proton channel.
What happens?
• Protons cannot flow back into the mitochondrial matrix through ATP synthase.
• This stops ATP production (oxidative phosphorylation halts).
• The proton gradient builds up, electron transport chain slows down because the gradient becomes too strong to pump more protons.
• Cells can’t make enough ATP, leading to energy crisis.
oligomycin primarily binds to the F₀ subunit of ATP synthase, not the F₁ subunit. Here’s the clarification:
• F₀ subunit: The membrane-embedded part of ATP synthase that forms the proton channel through which protons flow back into the mitochondrial matrix.
• Oligomycin binds to F₀, blocking this proton channel and preventing proton flow.
What is Aurovertin?
• It inhibits the F₁ subunit of ATP synthase.
• Specifically, it binds to the beta subunit of F₁, preventing the catalytic activity.
• This stops the enzyme from synthesizing ATP even if protons flow through F₀.
Yes, exactly.
Aurovertin inhibits the beta catalytic subunit of the F₁ portion of ATP synthase — the site where ADP and inorganic phosphate (Pi) are combined to form ATP.
What it does:
• It does not stop proton flow (unlike oligomycin).
• Instead, it blocks the actual chemical reaction:
ADP + Pi → ATP
by preventing the necessary conformational changes in the beta subunit that allow this binding and conversion to happen.
So:
• Protons may still move.
• But ATP is not formed because ADP and Pi cannot be properly joined.
1 NADH donates 2 electrons to the ETC.
• These electrons travel through Complex I, III, and IV.
• In total, this leads to 10 protons pumped into the intermembrane space:
• 4 from Complex I
• 4 from Complex III
• 2 from Complex IV
• ATP synthase uses about 4 protons to make 1 ATP:
• 3 for ATP formation
• 1 for transporting ADP and phosphate
Note that:
1 ATP is made for every 3–4 protons that flow through ATP synthase
• So:
• NADH → makes 10 protons overall → 10 ÷ 3–4 = ~3 ATP
• FADH₂ → 6 protons overall → 6 ÷ 3–4 = ~2 ATP
But today we say ~2.5 ATP per NADH and ~1.5 ATP per FADH₂ due to losses (like moving ATP out of mitochondria).
Based on this:
estimate of ATP per glucose is:
• Glycolysis:
• 2 ATP
• 2 NADH → 2 × 3 = 6 ATP
• Pyruvate to Acetyl-CoA:
• 2 NADH → 2 × 3 = 6 ATP
• Krebs Cycle:
• 2 ATP (as GTP)
• 6 NADH → 6 × 3 = 18 ATP
• 2 FADH₂ → 2 × 2 = 4 ATP
• Total = 38 ATP
This estimate assumes:
• Each NADH gives 3 ATP
• Each FADH₂ gives 2 ATP
• No energy loss
Modern science says ~30–32 ATP:
Because:
• Each NADH actually gives ~2.5 ATP
• Each FADH₂ gives ~1.5 ATP
• Some protons are used for transport (e.g. ATP out of the mitochondria, NADH shuttle into mitochondria)
• Shuttle systems (malate-aspartate or glycerol-3-phosphate) affect the final ATP from glycolytic NADH
Giving 30-32ATP instead. I’ll pick the old one sha.
Here are MCAT-style practice questions on oxidative phosphorylation — answers will follow in a separate message, as you requested:
- Which of the following directly donates electrons to Complex I of the electron transport chain?
A. FADH₂
B. NADH
C. Coenzyme Q
D. Cytochrome c
- How many protons are pumped across the mitochondrial membrane as a result of electrons transferred from one NADH molecule?
A. 4
B. 6
C. 8
D. 10
- Which complex of the ETC is not a proton pump?
A. Complex I
B. Complex II
C. Complex III
D. Complex IV
- What is the role of oxygen in oxidative phosphorylation?
A. It pumps protons into the intermembrane space.
B. It donates electrons to Complex IV.
C. It accepts electrons at the end of the chain to form water.
D. It transports electrons between Complex III and Complex IV.
- Which molecule is primarily responsible for transferring electrons from Complex I and II to Complex III?
A. NAD⁺
B. Cytochrome c
C. Coenzyme Q (ubiquinone)
D. ATP synthase
- In the absence of oxygen, oxidative phosphorylation stops because:
A. Complex I stops producing NADH
B. The proton gradient increases indefinitely
C. There is no final electron acceptor
D. ATP synthase becomes overactive
- ATP synthase produces ATP by:
A. Using the energy of electrons directly
B. Phosphorylating ADP using energy from glycolysis
C. Facilitating active transport of ATP out of the cell
D. Using the proton gradient to power phosphorylation of ADP
- The proton-motive force across the inner mitochondrial membrane is generated by:
A. Passive diffusion of protons
B. Oxidation of oxygen in the matrix
C. Active pumping of protons into the matrix
D. Electron transport-driven proton pumping into the intermembrane space
- Which of the following best describes the function of thermogenin in brown adipose tissue?
A. Stimulates Complex V to make more ATP
B. Inhibits Complex IV to generate heat
C. Allows protons to bypass ATP synthase, releasing heat
D. Binds oxygen more efficiently than hemoglobin
- If a poison blocks the transfer of electrons from Complex III to Complex IV, what will be the result?
A. Oxygen consumption will increase
B. NADH levels will drop dramatically
C. ATP production will increase
D. The proton gradient will not be maintained
Let me know if you want them categorized by topic (e.g. inhibitors, complexes, energy yield, etc.). Now I’ll send you the answers and explanations next.
Great! Here’s the answer key and explanations for the MCAT-style questions on oxidative phosphorylation, categorized by topic:
CATEGORY 1: Electron Transport Chain Basics
- Which of the following directly donates electrons to Complex I?
Correct answer: B. NADH
Explanation:
NADH donates electrons to Complex I (NADH dehydrogenase), initiating the ETC.
- How many protons are pumped from one NADH molecule?
Correct answer: D. 10
Explanation:
Electrons from NADH allow:
• Complex I to pump 4 protons
• Complex III to pump 4 protons
• Complex IV to pump 2 protons
= Total: 10 protons
- Which complex does not pump protons?
Correct answer: B. Complex II
Explanation:
Complex II (succinate dehydrogenase) transfers electrons to CoQ but does not pump protons.
- What is the role of oxygen in oxidative phosphorylation?
Correct answer: C. It accepts electrons at the end of the chain to form water.
Explanation:
Oxygen is the final electron acceptor, combining with electrons and protons to form water in Complex IV.
- Which molecule transfers electrons from Complex I and II to Complex III?
Correct answer: C. Coenzyme Q (ubiquinone)
Explanation:
CoQ accepts electrons from both Complex I and II and shuttles them to Complex III.
CATEGORY 2: Oxygen and ETC Dependency
- Why does oxidative phosphorylation stop without oxygen?
Correct answer: C. There is no final electron acceptor
Explanation:
Without oxygen, electrons cannot flow through Complex IV, and the entire ETC backs up, halting ATP production.
- How does ATP synthase produce ATP?
Correct answer: D. Using the proton gradient to power phosphorylation of ADP
Explanation:
Protons flow through ATP synthase (Complex V), which uses this energy to convert ADP + Pi into ATP.
- How is the proton-motive force created?
Correct answer: D. Electron transport-driven proton pumping into the intermembrane space
Explanation:
As electrons move through complexes I, III, and IV, protons are actively pumped into the intermembrane space, creating the gradient.
CATEGORY 3: Thermogenesis and Inhibition
- What does thermogenin do in brown fat?
Correct answer: C. Allows protons to bypass ATP synthase, releasing heat
Explanation:
Thermogenin (UCP1) creates a proton leak — protons bypass ATP synthase, and the energy is released as heat instead of making ATP.
- What happens if the transfer of electrons from Complex III to IV is blocked?
Correct answer: D. The proton gradient will not be maintained
Explanation:
If electrons can’t reach Complex IV, the ETC stalls, proton pumping stops, and ATP production halts due to loss of the gradient.
Let me know if you want a few more questions or flashcards on inhibitors, energy yield, or specific diseases tied to oxidative phosphorylation!
What is cellular respiration
What’s the total ATP after this ?
Note; F₁ subunit
Explanation: The F₁ portion of ATP synthase protrudes into the matrix and contains the catalytic sites where ADP and Pi combine to form ATP.
- Answer: C) 3-4 protons
Explanation: About 3-4 protons passing through ATP synthase are required to generate one ATP molecule, accounting for both ATP synthesis and phosphate transport.
Cellular respiration is the process by which cells break down glucose (or other fuels) to produce ATP, the energy currency of the cell.
It has three main stages:
1. Glycolysis (in cytoplasm)
2. Krebs Cycle (in mitochondrial matrix)
3. Electron Transport Chain & Oxidative Phosphorylation (in inner mitochondrial membrane)
Here’s a concise overview of cellular respiration, followed by a breakdown of its stages and ATP yield:
What is Cellular Respiration?
Cellular respiration is the process by which cells break down glucose (or other fuels) to produce ATP, the energy currency of the cell.
It has three main stages:
1. Glycolysis (in cytoplasm)
2. Krebs Cycle (in mitochondrial matrix)
3. Electron Transport Chain & Oxidative Phosphorylation (in inner mitochondrial membrane)
Stage-by-Stage Breakdown:
- Glycolysis (Anaerobic – no oxygen needed)
• Location: Cytoplasm
• Glucose (6C) → 2 Pyruvate (3C)
• Products:
• 2 ATP (net gain)
• 2 NADH
• No CO₂ released - Pyruvate to Acetyl-CoA (Link Reaction)
• Location: Mitochondrial matrix
• Each Pyruvate → 1 Acetyl-CoA
• Products per glucose:
• 2 NADH
• 2 CO₂ - Krebs Cycle (Citric Acid Cycle)
• Location: Mitochondrial matrix
• Each Acetyl-CoA → Full turn of cycle
• Products per glucose (2 turns):
• 2 ATP
• 6 NADH
• 2 FADH₂
• 4 CO₂ - Electron Transport Chain & Oxidative Phosphorylation
• Location: Inner mitochondrial membrane
• NADH & FADH₂ donate electrons → proton gradient → ATP synthase makes ATP
• Oxygen is final electron acceptor → H₂O formed
• Yields:
• ~2.5 ATP per NADH
• ~1.5 ATP per FADH₂
Total ATP Yield (Theoretical Maximum - Aerobic)
Source ATP Yield
Glycolysis 2 ATP + 2 NADH = ~7 ATP
Pyruvate → Acetyl-CoA 2 NADH = ~5 ATP
Krebs Cycle 2 ATP + 6 NADH + 2 FADH₂ = ~20 ATP
Total ~32 ATP per glucose
(Some books say 36-38 ATP using older estimates like 3 ATP/NADH and 2 ATP/FADH₂)
Let me know if you want flashcards, MCQs, or a simplified version of each step!
