Chapter 20 : Respiration
Respiration - Comprehensive Study Notes
Scope covered: glycolysis, link reaction, Krebs cycle, oxidative phosphorylation (electron transport chain and chemiosmosis), fermentation, aerobic vs anaerobic energy yields, regulation (PFK), diffusion processes in membranes, and typical exam-style questions with answers.
Glycolysis
Occurs in the cytosol; step-by-step series of chemical reactions, each catalysed by an enzyme.
Key features:
Phosphorylation events occur during glycolysis.
Net output per glucose molecule:
2 ATP (via substrate-level phosphorylation, SLP).
2 NADH produced.
2 pyruvate molecules formed.
Oxygen is not required for glycolysis to occur.
The end products are not CO2 and H2O; CO2 is released later in the link reaction and Krebs cycle, and water is formed during oxidative phosphorylation, not glycolysis.
Specific steps highlighted in the transcript:
Reaction 1: glucose → glucose-6-phosphate (phosphorylation).
Reaction 3: fructose-6-phosphate → fructose-1,6-bisphosphate (phosphorylation).
Correct statements (from the transcript): 1, 2, and 3 are factual; statement 4 is incorrect because glycolysis does not end with CO2 and H2O.
Link Reaction (Pyruvate Oxidation) & Entry to Krebs Cycle
Location: mitochondrial matrix.
Pyruvate (3C) is decarboxylated and combined with CoA to form acetyl-CoA (2C); release of CO2 occurs.
Reducing equivalents produced: NADH from each pyruvate; per glucose (2 pyruvate) → 2 NADH + 2 CO2 + 2 acetyl-CoA.
Acetyl-CoA then enters the Krebs cycle as the 2C acetyl unit.
Krebs Cycle (Citric Acid Cycle)
Location: mitochondrial matrix.
Key sequence:
Acetyl-CoA (2C) combines with oxaloacetate (4C) to form citrate (6C).
Citrate undergoes oxidative decarboxylation to form a 5C compound; CO2 is released.
The 5C compound undergoes oxidative decarboxylation to yield a 4C compound (oxaloacetate), regenerating the cycle.
Decarboxylation events occur in stages 1, 2, and 3:
Stage 1: Pyruvate → acetyl-CoA (oxidative decarboxylation) before Krebs cycle proper.
Stage 2: citrate → 5C compound (oxidative decarboxylation).
Stage 3: 5C → 4C compound (oxidative decarboxylation).
Reducing equivalents per acetyl-CoA turn:
3 NADH, 1 FADH2, and 1 ATP (substrate-level phosphorylation, often shown as GTP in some textbooks).
Per glucose (two turns of the cycle):
6 NADH, 2 FADH2, 2 ATP (via SLP).
Electron Transport Chain and Oxidative Phosphorylation (OP) / Chemiosmosis
Large protein complexes in the inner mitochondrial membrane transfer electrons via redox reactions, releasing energy.
Proton pumping:
Energy from electron flow is used to pump protons (H+) from the mitochondrial matrix to the intermembrane space.
The inner membrane is impermeable to protons, creating a proton motive force (electrochemical gradient).
ATP synthesis:
Protons flow back to the matrix through ATP synthase, driving phosphorylation of ADP to ATP.
Oxygen serves as the final electron acceptor, combining with electrons and H+ to form water via cytochrome oxidase.
Contributions to ATP yield (as used in the notes):
Each NADH yields ≈ 3 ATP.
Each FADH2 yields ≈ 2 ATP.
Overall message: OP (via chemiosmosis) generates most ATP in aerobic respiration; NADH and FADH2 are oxidized to NAD+ and FAD, enabling continued glycolysis, link reaction, and Krebs cycle.
Formula for typical ATP accounting (per glucose, using the noted convention):
Glycolysis (net) = 2 ATP + 2 NADH
Link reaction (per glucose) = 2 NADH + 2 CO2
Krebs cycle (per glucose) = 6 NADH + 2 FADH2 + 2 ATP
Oxidative phosphorylation yields:
From NADH: 3 ATP per NADH, so 6 NADH → 18 ATP
From FADH2: 2 ATP per FADH2, so 2 FADH2 → 4 ATP
Total ATP per glucose in this accounting:
Note: Some modern textbooks use ~2.5 ATP per NADH and ~1.5 ATP per FADH2; the notes here use the older convention of 3 and 2 respectively.
Other important outcomes:
Regeneration of NAD+ and FAD so glycolysis and the Krebs cycle can continue.
Water is produced at the end of the chain when O2 accepts electrons and protons.
Protons, Membranes, and Diffusion (Why protons move through protein channels)
Question: Protons diffuse through protein channels in the membrane during OP. Why?
Answer (from notes):
Protons are charged and water-soluble, and the hydrophobic core of the phospholipid bilayer (non-polar fatty acid tails) is impermeable to charged particles.
Therefore, protons diffuse through specific protein channels/complexes in the membrane rather than directly through the lipid bilayer.
Related recall: The hydrophobic core of the inner mitochondrial membrane inhibits diffusion of protons unless a proton channel (ATP synthase) or other transport proteins provide a path.
Regulation of Glycolysis via PFK (Phosphofructokinase)
PFK is a key regulatory enzyme controlling the rate of glycolysis; it catalyses the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate.
Effect of ATP concentration on PFK (from Fig. 7.1 discussion):
At a low fructose-6-phosphate concentration (1.0 mM): high ATP greatly reduces PFK activity (from 92 to 26 arbitrary units).
At a higher fructose-6-phosphate concentration (2.5 mM): high ATP has only a minimal effect on PFK activity, allowing glycolysis to proceed at higher substrate levels.
Mechanism of control (as described):
ATP acts as an allosteric regulator (negative feedback) by binding to an allosteric site on PFK.
This binding changes the conformation of PFK, reducing its affinity for fructose-6-phosphate and lowering the rate of glycolysis when ATP levels are high.
The overall rationale: when cellular energy (ATP) is abundant, glycolysis slows down to prevent excess ATP production; when energy is needed, glycolysis proceeds more rapidly.
Summary statement: ATP provides negative feedback control of glycolysis through allosteric inhibition of PFK, modulating the rate of glycolysis in response to cellular energy needs.
Fermentation and Anaerobic Respiration
When mitochondria ATP synthase is inhibited or oxygen is absent, cells rely on glycolysis followed by fermentation to regenerate NAD+ for glycolysis to continue.
Key fermentation outcomes:
In anaerobic conditions, respiration produces ATP only via glycolysis (net 2 ATP per glucose).
Fermentation does not yield additional ATP itself; its main role is to regenerate NAD+ from NADH so glycolysis can continue.
Types of fermentation (as discussed in the notes):
In yeast (alcoholic fermentation): pyruvate is decarboxylated to ethanal (acetaldehyde), which is reduced to ethanol; CO2 is released during decarboxylation.
In mammalian (lactate) fermentation: pyruvate is reduced to lactate by lactate dehydrogenase; NAD+ is regenerated.
Purpose of fermentation:
Regenerate NAD+ to sustain glycolysis under anaerobic conditions.
Important implications for ATP yield:
Overall net ATP per glucose remains 2 (from glycolysis) in anaerobic conditions; no additional ATP is produced during fermentation itself.
Energy Yields: Aerobic vs Anaerobic Respiration
General explanation for the lower ATP yield in anaerobic respiration:
In aerobic respiration, most ATP is produced during oxidative phosphorylation (OP) via the electron transport chain, using NADH and FADH2 as electron carriers.
In anaerobic respiration, the electron transport chain is not used (or is not fully linked to NADH/FADH2 oxidation) due to the absence of a final electron acceptor like oxygen; only glycolysis plus fermentation occurs.
Specific statements featured in the exercises:
Three statements explain low ATP yield: (1) energy in chemical bonds of lactate can be obtained only after oxidation to pyruvate; (2) the ETC is responsible for most energy transfer to ATP (absent in strict anaerobes); (3) decarboxylation of pyruvate in yeast anaerobically is not linked to ATP synthesis; (4) glycolysis yields only 2 ATP per glucose.
Correct combination: 1, 3, and 4 explain parts of why anaerobic yield is lower; glycolysis yields only 2 ATP (SLP) and the rest of the energy is trapped in fermentation products (lactate/ethanol).
Practical calculation (from the self-attempt): to match 38 ATP from aerobic respiration using only the 2 ATP per glucose from glycolysis (anaerobic), glycolysis would need to run about 19 times faster: 38 / 2 = 19.
Oxygen’s Role in Aerobic Respiration
Oxygen’s essential roles:
It is the final electron acceptor at the end of the electron transport chain, combining with electrons and protons to form water (via cytochrome c oxidase).
This regeneration of NAD+ and FAD allows glycolysis, the link reaction, and Krebs cycle to continue.
Oxygen’s role maintains the flow of electrons through the chain and sustains the proton gradient used for ATP synthesis via chemiosmosis.
In the absence of oxygen:
The electron transport chain cannot operate because there is no final electron acceptor.
NADH, FADH2, and electron carriers remain reduced; proton pumping stops; ATP production via OP halts.
Cells rely on anaerobic glycolysis and fermentation to generate a limited amount of ATP.
ATP Production Without Oxygen (Anaerobic Pathways)
How ATP is produced in absence of oxygen:
Glycolysis occurs in the cytosol and produces a net of 2 ATP per glucose via substrate-level phosphorylation.
Fermentation follows glycolysis to regenerate NAD+ so glycolysis can continue.
Details on pyruvate fate are not required for ATP yield; the key is NAD+ regeneration and maintenance of glycolysis.
Facilitated Diffusion (Glucose Uptake) – Definition and Role
Glucose uptake into cells occurs via facilitated diffusion.
Characteristics:
Passive process driven by concentration gradient (downhill transport).
Uses specific transport proteins (channel or carrier proteins).
Does not require energy (no direct ATP expenditure).
Allows more rapid exchange than simple diffusion.
This mechanism is important for supplying glucose to cells for glycolysis, particularly when extracellular glucose concentration is high enough to drive transport.
NAD+/FADH2 in Cellular Respiration (Roles and Recycling)
NAD+ and FAD act as coenzymes and hydrogen/electron carriers.
Roles:
Accept electrons (and H+) during glycolysis, the link reaction, and Krebs cycle to form NADH and FADH2.
Transport electrons to the electron transport chain where they are oxidised back to NAD+ and FAD, regenerating these cofactors for continued metabolism.
Outcomes:
Regeneration of NAD+ and FAD is essential for continued glycolysis, link reaction, and Krebs cycle to proceed.
Important note: NADP+/NADPH is separate and not meant for this pathway (don’t confuse with NAD/NADH).
Practical Summary: How the Pathways Tie Together (Integrated View)
Glycolysis (cytosol): glucose → 2 pyruvate + 2 NADH + 2 ATP (net).
Link reaction (mitochondrial matrix): 2 pyruvate → 2 acetyl-CoA + 2 CO2 + 2 NADH.
Krebs cycle (mitochondrial matrix): per glucose, 6 NADH, 2 FADH2, 2 ATP (via SLP).
Oxidative phosphorylation (inner mitochondrial membrane): NADH yields ~3 ATP; FADH2 yields ~2 ATP; O2 is the final electron acceptor; H+ gradient drives ATP synthesis.
Total ATP per glucose under the notes’ convention: (Note: some modern figures use 25–28 ATP per glucose depending on the ATP yield per NADH/FADH2; the notes use 38.)
Under anaerobic conditions: glycolysis + fermentation; net 2 ATP per glucose; NAD+ regeneration allows continued glycolysis; lactate or ethanol produced depending on organism.
Common Exam-Style Insights (based on the transcript)
Answer patterns often emphasize:
Decarboxylation steps in the Krebs-related decarboxylation sequence (pyruvate to acetyl-CoA; citrate to 5C; 5C to 4C).
Distinctions between glycolysis products and downstream CO2/H2O production (CO2 released in link reaction and Krebs cycle; water produced in OP).
The role of oxygen in regenerating NAD+ and allowing continuous flow through the ETC; oxygen absence halts ETC.
The mechanism of ATP control over glycolysis via ATP’s allosteric inhibition of PFK, i.e., negative feedback and end-product regulation.
The difference in ATP yield and glucose consumption rates between aerobic and anaerobic conditions, with anaerobic pathways yielding far less ATP per glucose.
The concept of facilitation diffusion for glucose uptake and its energy implications.
Key Equations and Numerical Highlights (LaTeX)
Total ATP per glucose in aerobic respiration (as per notes):
NADH to ATP (old convention used in notes):
Each NADH yields
Each FADH2 yields
Glucose to pyruvate in glycolysis:
ext{Glucose}
ightarrow 2 ext{ Pyruvate} A
ext{(net ATP }=2, ext{ net NADH }=2).Pyruvate to acetyl-CoA (link reaction): per glucose two units:
6 ext{ NADH} + 2 ext{ FADH}_2 + 2 ext{ ATP}.Glycolysis and fermentation: net ATP from glycolysis is 2; fermentation regenerates NAD+ but does not produce additional ATP.
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