Table of Contents
Overview and Role of Cellular Respiration
Cellular respiration is the central catabolic pathway by which cells systematically break down energy-rich organic molecules (mainly glucose, but also fatty acids and amino acids) and convert the released free energy into a usable form, primarily ATP. Unlike fermentation, it uses an electron transport chain and (typically) an inorganic molecule as the final electron acceptor.
In most eukaryotes and many prokaryotes, cellular respiration is an aerobic process: molecular oxygen $O_2$ acts as the final electron acceptor and is reduced to water. In other organisms or under special conditions, respiration can be anaerobic, using other inorganic acceptors such as nitrate or sulfate instead of oxygen.
A simplified, overall equation for aerobic respiration of glucose is:
$$
\text{C}_6\text{H}_{12}\text{O}_6 + 6\,\text{O}_2 \longrightarrow 6\,\text{CO}_2 + 6\,\text{H}_2\text{O} + \text{energy (ATP + heat)}
$$
This equation hides the many intermediate steps and the fact that the energy from glucose is not released all at once, but in a controlled series of reactions.
Key Functions of Cellular Respiration
- Energy conservation
The main function is to convert the chemical energy of nutrients into ATP via oxidative phosphorylation and substrate-level phosphorylation. - Generation of reducing power
High-energy electrons are transferred to electron carriers such as NAD$^+$ and FAD, forming NADH and FADH$_2$. These reduced carriers drive the electron transport chain. - Metabolic hub
Intermediates of respiration (e.g., pyruvate, acetyl-CoA, intermediates of the citric acid cycle) are branching points for anabolic and catabolic pathways, connecting carbohydrate, lipid, and protein metabolism. - Controlled oxidation
By oxidizing substrates stepwise, cells avoid destructive heat release and instead harness free energy in small, usable portions.
General Structure of Cellular Respiration
Although details differ between organisms and between prokaryotes and eukaryotes, cellular respiration typically comprises three tightly connected stages (which have their own chapters):
- Glycolysis
- Occurs in the cytosol.
- Splits one glucose molecule ($6$ carbons) into two molecules of pyruvate ($3$ carbons each).
- Produces a small net amount of ATP and NADH via substrate-level phosphorylation and redox reactions.
- Oxidation of Pyruvate and Citric Acid Cycle
- In eukaryotes, pyruvate is transported into the mitochondrial matrix, where it is converted to acetyl-CoA (with release of CO$_2$ and formation of NADH).
- Acetyl-CoA enters the citric acid (Krebs) cycle, which completes the oxidation of the carbon skeleton to CO$_2$ and generates additional NADH, FADH$_2$, and some ATP (or GTP).
- Electron Transport Chain (ETC) and Oxidative Phosphorylation
- In eukaryotes, located in the inner mitochondrial membrane.
- NADH and FADH$_2$ donate electrons to a chain of electron carriers.
- The energy released as electrons move “downhill” to the final electron acceptor (usually $O_2$) is used to pump protons and create a proton gradient.
- The return flow of protons through ATP synthase drives ATP synthesis.
The integration of these stages turns the chemical energy of glucose into a yield of roughly 30–32 ATP per glucose molecule in many eukaryotic cells under ideal aerobic conditions (the exact number varies with cell type and transport efficiencies).
Chemical Logic: Oxidation, Reduction, and Energy Release
Cellular respiration is fundamentally a series of redox reactions:
- Oxidation: loss of electrons or hydrogen (often associated with gain of oxygen).
- Reduction: gain of electrons or hydrogen.
In the overall reaction, glucose is oxidized to CO$_2$, and oxygen is reduced to H$_2$O. However, electrons are not transferred directly from glucose to oxygen. Instead, they pass through carriers:
- NAD$^+$ + 2e$^-$ + 2H$^+$ $\rightarrow$ NADH + H$^+$
- FAD + 2e$^-$ + 2H$^+$ $\rightarrow$ FADH$_2$
These redox reactions release free energy in small steps. Each transfer from a higher to a lower energy state (from less electronegative to more electronegative carriers) is coupled to:
- synthesis of ATP (directly or indirectly), or
- establishment of ion gradients (especially H$^+$) across membranes.
Substrate-Level Phosphorylation vs. Oxidative Phosphorylation
Cellular respiration produces ATP via two mechanistically distinct processes:
Substrate-Level Phosphorylation
Here, a phosphate group is directly transferred from a phosphorylated intermediate (a “high-energy” substrate) to ADP, forming ATP:
$$
\text{ADP} + \text{P–substrate} \longrightarrow \text{ATP} + \text{substrate}
$$
Characteristics:
- Occurs in specific steps of glycolysis and the citric acid cycle.
- Does not require an electron transport chain or a membrane gradient.
- Produces only a small fraction of the total ATP yield.
Oxidative Phosphorylation
Here, ATP synthesis is driven by the energy released from electron transfer along the ETC:
- Electrons from NADH and FADH$_2$ pass through the ETC to an inorganic final acceptor (typically $O_2$).
- The released energy pumps protons across a membrane, generating an electrochemical proton gradient (proton motive force).
- Protons flowing back through ATP synthase power the phosphorylation of ADP:
$$
\text{ADP} + \text{P}_i + \text{H}^+_{\text{outside}} \xrightarrow{\text{ATP synthase}} \text{ATP} + \text{H}^+_{\text{inside}}
$$
Characteristics:
- Accounts for the majority of ATP produced in aerobic respiration.
- Depends on intact membranes (inner mitochondrial membrane in eukaryotes, plasma membrane in many prokaryotes).
- Is tightly linked to oxygen consumption in aerobic organisms.
Cellular Localization of Respiratory Processes
The compartmentation of cellular respiration differs between eukaryotes and prokaryotes.
Eukaryotic Cells
- Cytosol: Glycolysis (production of pyruvate, ATP, and NADH).
- Mitochondrial matrix:
- Pyruvate oxidation to acetyl-CoA.
- Citric acid cycle (CO$_2$ production, generation of NADH and FADH$_2$).
- Inner mitochondrial membrane:
- Electron transport chain.
- ATP synthase and oxidative phosphorylation.
- Intermembrane space:
- Accumulation of protons pumped by the ETC, forming the gradient used by ATP synthase.
The double-membrane structure of mitochondria and their own DNA and ribosomes are consistent with their endosymbiotic origin and are essential for compartmentalized respiration.
Prokaryotic Cells
- Cytosol:
- Glycolysis, citric acid cycle (or variants), and other central metabolic reactions.
- Plasma membrane:
- Electron transport chains and ATP synthase.
- Proton gradients are built across the plasma membrane, with the periplasm (or outside environment) serving as the “outer” compartment.
Because prokaryotes lack mitochondria, they integrate respiration into the cell envelope system. Some prokaryotes possess additional internal membrane structures that increase surface area for electron transport (e.g., in nitrifying bacteria).
Aerobic vs. Anaerobic Respiration (Inorganic Electron Acceptors)
Cellular respiration is not restricted to oxygen as the final electron acceptor.
Aerobic Respiration
- Final acceptor: $O_2$.
- Products: CO$_2$, H$_2$O, ATP, and heat.
- Energy yield: High, because the difference in redox potential between the electron donors (e.g., NADH) and oxygen is large.
Anaerobic Respiration
Some microorganisms use other inorganic molecules as terminal electron acceptors when oxygen is absent:
- Nitrate ($\text{NO}_3^-$) $\rightarrow$ nitrite ($\text{NO}_2^-$), N$_2$O, or N$_2$.
- Sulfate ($\text{SO}_4^{2-}$) $\rightarrow$ sulfide (H$_2$S).
- Carbon dioxide (CO$_2$) $\rightarrow$ methane (CH$_4$) in methanogenic archaea.
- Fumarate or other organic acceptors in certain bacteria.
Differences from fermentation:
- Uses an electron transport chain and oxidative phosphorylation.
- Achieves higher ATP yields than fermentation, but usually lower than oxygen respiration because many alternative acceptors have less favorable redox potentials than $O_2$.
Such anaerobic respiratory processes are ecologically important (e.g., in nitrogen and sulfur cycles) and are critical in oxygen-poor environments such as sediments, swamps, and the intestines of animals.
Energy Yield and Efficiency
The theoretical energy yield of aerobic respiration for one molecule of glucose in many eukaryotic cells can be summarized approximately:
- Glycolysis: small ATP gain via substrate-level phosphorylation + NADH.
- Citric acid cycle: more ATP (or GTP) + large amounts of NADH and FADH$_2$.
- Oxidative phosphorylation: majority of ATP synthesized from NADH and FADH$_2$.
Although exact ATP numbers vary, the pattern is clear:
- Substrate-level phosphorylation contributes a modest amount of ATP.
- Oxidative phosphorylation is the dominant source of ATP.
The overall process is quite efficient in terms of biological energy conversion, capturing a substantial portion of glucose’s free energy in ATP. The rest is lost as heat, which is also biologically significant (e.g., for thermoregulation in warm-blooded animals).
Integration with Other Metabolic Pathways
Cellular respiration is not a closed, one-way “burning” of glucose; instead, it operates as a network hub:
- Entry points:
- Carbohydrates can enter as glucose or other sugars that feed into glycolysis.
- Fatty acids are degraded via $\beta$-oxidation to acetyl-CoA, which enters the citric acid cycle.
- Amino acids, after deamination, enter at various points (pyruvate, acetyl-CoA, or citric acid cycle intermediates).
- Exit points (biosynthesis):
- Citric acid cycle intermediates serve as precursors for amino acids, nucleotides, and other biomolecules.
- Acetyl-CoA is a central precursor for lipid and sterol synthesis.
Because of this, cellular respiration must be dynamically regulated to balance ATP production with the cell’s needs for biosynthetic precursors.
Regulation of Cellular Respiration (Conceptual Overview)
Although detailed mechanisms are addressed in other chapters, the regulation of cellular respiration follows a few general principles:
- Feedback inhibition by ATP:
High ATP levels signal that energy demand is low. Key regulatory enzymes in glycolysis and the citric acid cycle are inhibited, slowing down the flow of carbon. - Activation by ADP/AMP:
Accumulation of ADP or AMP signals energy demand. These molecules often activate rate-limiting enzymes, accelerating respiration. - Control by NADH/NAD$^+$ ratio:
A high NADH/NAD$^+$ ratio indicates a reduced state of the cell and suppresses further oxidative steps. Re-oxidation of NADH by the electron transport chain is thus essential to keep respiration running. - Hormonal and tissue-specific control in multicellular organisms:
Hormones (e.g., insulin, glucagon, adrenaline) and tissue-specific enzyme expression fine-tune how strongly different tissues rely on cellular respiration at any given time.
Physiological and Ecological Significance
- At the cellular level:
Cellular respiration sustains ATP-dependent processes such as active transport, biosynthesis, mechanical work (e.g., muscle contraction), and maintenance of ion gradients. - At the organismal level:
The rate and pattern of respiration are linked to metabolic rate, thermoregulation, and performance capacity, and they underpin differences between ectotherms and endotherms. - At the ecosystem level:
Cellular respiration is the “reverse” of photosynthesis in the global carbon cycle. It returns CO$_2$ to the atmosphere and closes the loop of carbon and energy flow from producers to consumers and decomposers.
In summary, cellular respiration is the central catabolic engine of most living cells, converting the energy stored in organic molecules into ATP via a coordinated series of oxidation–reduction reactions, linked by electron carriers, ion gradients, and membrane-bound machinery.