Life thrives on organization, a principle deeply rooted in the laws of thermodynamics, necessitating a constant energy supply. For living organisms, energy is the driving force behind every function, from the macroscopic movements we observe to the intricate molecular processes within cells. While we often associate energy with food and calories, at the cellular level, the universal energy currency is ATP (Adenosine Triphosphate). Cellular respiration is the fundamental process that converts the energy stored in the food we consume, such as sugars, into ATP, the usable energy form for our cells.
Cellular respiration is essentially the breakdown of energy-rich molecules, with glucose being a prime example, to extract energy. This vital process occurs in both plant and animal cells. The energy liberated from glucose breakdown is then stored within cells as ATP, ready to power cellular activities. The overall process of cellular respiration can be represented by the following simplified equation:
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Figure 1: Overview of Cellular Respiration. This diagram illustrates the three main stages of cellular respiration: Glycolysis, Krebs Cycle, and Electron Transport Chain, highlighting their locations and key outputs.
Cellular respiration unfolds in three interconnected and crucial stages:
1. Glycolysis: This initial stage marks the breakdown of glucose, a six-carbon sugar, into two molecules of pyruvate, each containing three carbons. In this process, a net gain of 2 ATP molecules is directly produced per glucose molecule. Furthermore, Glycolysis also generates 2 molecules of NADH, an important electron carrier. Notably, glycolysis occurs in the cytoplasm of the cell and does not require oxygen, making it an anaerobic process.
2. Krebs Cycle (Citric Acid Cycle): Also known as the Citric Acid Cycle, the Krebs Cycle takes the pyruvate molecules produced in Glycolysis and further processes them. For each initial glucose molecule, the Krebs Cycle, through two turns, generates a further 2 ATP molecules. More importantly, it produces a wealth of high-energy electron carriers, specifically NADH and FADH2, which are crucial for the next stage, the electron transport chain. The Krebs Cycle takes place within the mitochondrial matrix and is an aerobic process, meaning it requires oxygen.
3. Electron Transport Chain (ETC): The final stage, the electron transport chain, is where the majority of ATP is generated. Utilizing the NADH and FADH2 molecules produced in Glycolysis and the Krebs Cycle, the ETC harnesses the energy from their electrons to create a proton gradient across the inner mitochondrial membrane. This gradient then drives the synthesis of approximately 32 ATP molecules per glucose molecule through a process called oxidative phosphorylation. Like the Krebs Cycle, the ETC occurs in the mitochondria and is an aerobic process, critically dependent on oxygen.
Key Players in the Cellular Respiration Pathway
Understanding cellular respiration necessitates familiarity with its key molecular players:
- Glucose: A simple six-carbon sugar. Glucose serves as the primary fuel source for cellular respiration, providing the initial energy input for the entire process.
- ATP (Adenosine Triphosphate): The principal energy currency of the cell. ATP is a high-energy molecule that stores and transports energy, readily releasing it to power various cellular activities.
- NADH (Nicotinamide Adenine Dinucleotide): A high-energy electron carrier. NADH is crucial for transporting electrons harvested during Glycolysis and the Krebs Cycle to the electron transport chain.
- FADH2 (Flavin Adenine Dinucleotide): Another high-energy electron carrier, similar in function to NADH. FADH2 also transports electrons to the electron transport chain, contributing to ATP production.
Glycolysis: The First Step in Energy Extraction
Glycolysis, the first stage of cellular respiration, initiates the breakdown of glucose to produce ATP. In this process, a single glucose molecule, containing six carbon atoms, is cleaved into two molecules of pyruvate, each containing three carbon atoms. This breakdown involves a series of enzyme-catalyzed reactions.
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Figure 2: The Glycolysis Pathway. This diagram details the two phases of glycolysis: the preparatory phase where ATP is invested, and the payoff phase where ATP and NADH are generated.
Glycolysis can be distinctly divided into two main phases:
1. Preparatory Phase (Investment Phase): The initial steps of glycolysis require an investment of energy. Glucose, in its original form, is not readily broken down. To initiate the process, energy in the form of 2 ATP molecules is invested. This ATP is used to add phosphate groups to the glucose molecule, resulting in a phosphorylated glucose molecule. These phosphate groups not only trap glucose within the cell but also destabilize the molecule, making it more reactive and primed for subsequent breakdown.
2. Payoff Phase: Following the energy investment in the preparatory phase, the payoff phase yields a net gain of energy. In this phase, the chemically modified glucose molecule is further processed through a series of reactions. These reactions result in the production of 4 ATP molecules and 2 NADH molecules. Since 2 ATP molecules were invested in the preparatory phase, the net ATP gain from glycolysis is 2 ATP. Additionally, two molecules of pyruvate are generated as the end product of glycolysis.
Krebs Cycle: Further Oxidation and Electron Harvesting
The pyruvate molecules produced at the end of glycolysis are transported from the cytoplasm into the mitochondria, specifically into the mitochondrial matrix. Before entering the Krebs Cycle, pyruvate undergoes a crucial preparatory step: conversion into acetyl coenzyme A (acetyl CoA). This conversion also involves the removal of one carbon atom (released as carbon dioxide) and the transfer of electrons to NAD+, generating NADH. Acetyl CoA is the molecule that then enters the Krebs Cycle.
The Krebs Cycle, a cyclical series of reactions, consists of eight enzyme-catalyzed steps (originally described as nine in the source text but commonly understood as eight steps in modern biochemistry). These steps can be broadly grouped into three stages:
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Entry of Acetyl CoA: Acetyl CoA, carrying two carbon atoms, enters the cycle by combining with a four-carbon molecule called oxaloacetate. This condensation reaction forms a six-carbon molecule called citrate, marking the beginning of the cycle.
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Carbon Dioxide Release and Energy Carrier Generation: In subsequent steps, two carbon atoms are removed from citrate in the form of carbon dioxide (CO2). These decarboxylation reactions are coupled with the generation of energy carriers. For each acetyl CoA entering the cycle, 3 molecules of NADH and 1 molecule of FADH2 are produced. Additionally, one molecule of ATP (or GTP, which is readily converted to ATP) is generated directly through substrate-level phosphorylation.
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Regeneration of Oxaloacetate: The final stages of the Krebs Cycle are dedicated to regenerating the initial four-carbon molecule, oxaloacetate. This regeneration is essential because oxaloacetate is required to accept another molecule of acetyl CoA, allowing the cycle to continue.
The primary outputs of the Krebs Cycle are ATP and, more significantly, a substantial amount of energized electrons carried by NADH and FADH2. These electron carriers are vital as they feed into the final stage of cellular respiration, the electron transport chain.
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Figure 3: The Krebs Cycle (Citric Acid Cycle). This diagram illustrates the cyclical nature of the Krebs cycle, highlighting the inputs, outputs, and regeneration of oxaloacetate.
Electron Transport Chain: The Major ATP Production Site
The mitochondrial electron transport chain (ETC) shares functional similarities with the electron transport chain found in chloroplasts during photosynthesis, although the specific molecules involved differ. The ETC is embedded within the inner mitochondrial membrane. NADH and FADH2 molecules, generated during Glycolysis and the Krebs Cycle, deliver their high-energy electrons to the electron transport chain.
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Figure 4: The Electron Transport Chain and Chemiosmosis. This diagram shows the flow of electrons through the ETC, the pumping of protons to create a gradient, and the generation of ATP by ATP synthase.
The electron transport chain is a series of protein complexes that facilitate a step-wise transfer of electrons from NADH and FADH2 to oxygen, the final electron acceptor. As electrons move through the chain, energy is released. This released energy is used to pump protons (H+) from the mitochondrial matrix across the inner mitochondrial membrane into the intermembrane space. This pumping action establishes a steep electrochemical gradient, with a higher concentration of protons in the intermembrane space compared to the matrix. This gradient represents stored potential energy.
The potential energy stored in the proton gradient is then harnessed to synthesize ATP. Protons flow down their concentration gradient, moving from the intermembrane space back into the mitochondrial matrix. This movement occurs through a protein complex called ATP synthase, which acts like a molecular turbine. The flow of protons through ATP synthase provides the energy needed to drive the phosphorylation of ADP (adenosine diphosphate) to ATP. This process of ATP synthesis, driven by the proton gradient established by the electron transport chain, is known as chemiosmosis or oxidative phosphorylation.
The final step in the electron transport chain involves the combination of electrons, protons, and oxygen to form water. Oxygen’s role as the final electron acceptor is crucial; without oxygen, the electron transport chain would stall, and ATP production would drastically decrease.
In summary, the electron transport chain’s action can be broken down as follows:
- Electron Delivery: NADH and FADH2, carrying electrons from Glycolysis and the Krebs Cycle, donate their electrons to the ETC.
- Proton Pumping: As electrons move through the ETC, energy is used to pump protons from the mitochondrial matrix to the intermembrane space, creating a proton gradient.
- Water Formation: Oxygen accepts electrons at the end of the ETC and combines with protons to form water.
- ATP Synthesis: Protons flow down their concentration gradient through ATP synthase, driving the synthesis of ATP.
The electron transport chain is responsible for generating the vast majority of ATP produced during cellular respiration. It is the culmination of the energy extraction processes initiated in glycolysis and furthered in the Krebs cycle, making it the powerhouse of the cell in terms of ATP production.
Cellular Respiration Tutorial by Dr. Katherine Harris is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
Funded by the U.S. Department of Education, College Cost Reduction and Access (CCRAA) grant award
