Breathing Life into Cells: Exploring the Mechanics of Cellular Respiration — Part 1 of 5
By Eva Fata
This is 1st Part in a 5 Part Series I’ve written comparing cellular respiration in normal cells versus cancer cells. In this part, I will be exploring cellular respiration in normal cells. For all parts, please see the links at the bottom of this article.
From Food To Energy
Cellular respiration is how your cells turn glucose and other food molecules into energy mostly in the form of adenosine triphosphate (ATP). These are called catabolic reactions. Catabolic reactions break down larger molecules into smaller pieces.
Cellular respiration can be broken down into 4 stages: glycolysis, pyruvate oxidation, citric acid cycle (Krebs cycle or TCA cycle) and oxidative phosphorylation.
The general chemical formula for cellular respiration is:
C₆H₁₂O₆+6 O₂⟶6 CO₂+6 H₂O + Energy
The energy released is in the form of ATP. This equation shows that glucose (C₆H₁₂O₆) and oxygen (O₂) react to form carbon dioxide (CO₂)and water (H₂O) thus releasing energy through the process. Because oxygen is required for this process it is considered aerobic.
Cellular respiration is important because it serves as a powerhouse for every living cell. Through the breakdown of organic molecules specifically glucose, cellular respiration allows for the necessary energy needed in the form of ATP. This energy fuels multiple different cellular processes which are needed for survival ranging from muscle contractions to the synthesis of essential biomolecules. Furthermore, cellular respiration regulates different metabolic pathways, ensures the efficient removal of waste products such as carbon dioxide, and optimizes the use of oxygen which is vital for sustaining life in aerobic organisms. Cellular respiration is a fundamental mechanism for the growth, survival and functionality of all living organisms.
Step 1. Glycolysis
This is how your cells get energy from the sugar you eat. In this step, the 6 carbon molecules break down into two separate pyruvate (also known as pyruvic acid) molecules which are in pairs of three. 2 molecules of ATP are made and 2 molecules of NADH. Within glycolysis, there are 2 phases.
The first phase/half of glycolysis is the “energy-requiring steps” and the second half is the “energy-releasing steps”. The first half prepares the six-carbon ring form of glucose for breaking down into two 3 carbon sugars. 2ATPs are used in this half to provide the needed energy for separation. The second half of glycolysis takes ATP and high-energy electrons from hydrogen atoms and then attaches them to NAD+. There are 2 ATP molecules which are used in the first half and four ATP molecules which get formed by substrate phosphorylation in the second half. This then further produces two ATP and two NADH molecules for the cell.
A deeper dive into this amazing process can be found HERE
Step 2. Pyruvate Oxidation
Pyruvate oxidation. This is a key process that connects glycolysis to the rest of the whole cellular respiration process. So as you remember from the last step above, glycolysis, there are 2 pyruvate molecules left which contain lots of energy. So this step helps retrieve the energy left in it, in the form of ATP. In prokaryotes (bacteria, archaea) this happens in the cytoplasm, and for eukaryotes (us, humans, animals, fungi) it happens in the matrix which is the innermost compartment within the mitochondria.
The overall goal of pyruvate oxidation is to convert pyruvate (a three-carbon molecule) into acetyl CoA a two-carbon molecule attached to coenzyme A which produces NADH and releases carbon dioxide in the process. Acetyl CoA will act as a fuel in the next stage which is the citric acid cycle (Krebs cycle).
Here is an overview of the whole process:
- A carboxyl group is removed from pyruvate, which thus releases a molecule of carbon dioxide into the surrounding environment. This then results in a two-carbon hydroxyethyl group attached to the enzyme (pyruvate dehydrogenase). This is one of the six carbon molecules which is extracted from the original glucose molecule. This step occurs twice, (remember that there are two pyruvate molecules from glycolysis) for each molecule of glucose metabolized, which means that 2 out of the 6 carbons will be removed at the end of both steps (glycolysis and pyruvate oxidation).
2. NAD+ is further reduced to NADH. The hydroxyethyl group undergoes oxidation. During the oxidation, the hydroxyethyl loses electrons and is then converted into an acetyl group (two-carbon molecule). The electrons are then picked by the electron carrier molecule NAD+, forming NADH. The high-energy electrons from NADH will later be used to produce ATP.
3. An acetyl group is transferred to coenzyme A (CoA — derived from vitamin B5) which results in acetyl CoA. The enzyme-attached acetyl group is further transported to produce a molecule of acetyl CoA. Acetyl CoA is then transferred to the citric acid cycle (Krebs cycle).
Note: whenever a carbon atom is removed, it is attached to 2 oxygen atoms, which produces carbon dioxide, one of the crucial end products of cellular respiration.
Citric Acid Cycle
The citric acid cycle takes place in the mitochondrial matrix in eukaryotes just like the pyruvate oxidation, in eukaryotes, it takes place in the cytoplasm. The citric acid is a closed loop which means that the molecule, oxaloacetate which is the last part of the cycle is regenerated and used in the first step again, which makes this cycle continuous. This cycle completes the oxidation of glucose by taking the pyruvates from glycolysis (as well as other pathways), by completing reactions and breaking them down into carbon dioxide molecules, and water molecules and generating ATP by oxidative phosphorylation.
The outcome of the citric acid cycle is the generation of one molecule of GTP which is equivalent to ATP, 2 carbon dioxide molecules. are released, the regeneration of oxaloacetate as well as 3 molecules NADH and 1 molecule of FADH2 which is generated through a redox reaction, which serves as electron carriers to the electron transport chain, in turn fuelling synthesis of ATP. A Deeper dive into this cool pathway can be found HERE and HERE.
Oxidative Phosphorylation
Oxidative phosphorylation takes place in the inner mitochondrial membrane and is a key component of cellular respiration.
Oxidative phosphorylation makes approximately 30–32 ATPs — the majority of ATP molecules throughout the whole process. The exact amount of ATP which is produced through oxidative phosphorylation varies depending on factors like the efficiency of the electron transport chain and the availability of oxygen. Oxidative phosphorylation is a critical process in cellular metabolism and serves as a major energy producer in eukaryotic cells. Oxidative phosphorylation ensures a continuous supply of energy which is needed to sustain many cellular processes and maintain cellular homeostasis. In all, oxidative phosphorylation is key for the survival, growth and functionality of aerobic organisms.
This process is made up of two parts: 1) Electron Transport Chain and 2) Chemiosmosis.
The electron transport chain is a collection of membrane-embedded proteins and organic molecules, which are organized into four large complexes labelled I, to IV. These can be found in the inner mitochondrial membrane in eukaryotes and in prokaryotes the electron transport chain components can be found in the plasma membrane.
The Main Functions of the Electron Transport Chain are as follows:
- Regenerates electron carriers. NADH and FADH pass their electrons to the electron transport chain, which turn back into NAD and FAD. This is key because these oxidized forms of the electron carriers will be used in glycolysis and the citric acid cycle and therefore must be available to keep the processes running.
- Makes a proton gradient. The transport chain builds and proton gradient across the inner mitochondrial membrane, with a larger concentration of H (H+ ions) in the intermembrane area and a lower concentration in the matrix of the mitochondria. This is a stored form of energy which can be used to make ATP.
Chemiosmosis (proton motive force):
In chemiosmosis, the protons travel down their electrochemical gradient through a portion of the ATP synthase powering it to make ATP — which is the ultimate goal. The complexes I, III, and IV of the electron transport chain are proton pumps. As these electrons move downhill, they capture and release energy and further use it to pump H ions from the matrix into the intermembrane space.
This forms a gradient across the inner mitochondrial membrane, also known as the proton motive force. However, like many ions, these protons cannot pass through the phospholipid bilayer because its core is too hydrophobic (water-fearing). So instead these H ions move down their concentration gradient, with the help of channel proteins which form hydrophilic tunnels across the membrane.
In the inner mitochondrial membrane, the H+ ions only have one channel available to them the protein ATP synthase. ATP synthase is like a turbine in a hydroelectric power plant. However, instead of being turned by water, it is turned by H ions which move through it. As the ATP synthase turns it adds a phosphate to ADP, which produces ATP. This is chemiosmosis, energy extracted from the proton gradient to produce ATP. Chemiosmosis generates about 90% of the ATP.
Hibernating animals such as bears use this process to produce heat rather than ATP to keep them warm!
The total amounts of ATP generated throughout the whole process of cellular respiration is about 30–32 ATP. 2 ATP are made in glycolysis, another 2 are made in the citric acid cycle and the rest come from oxidative phosphorylation
So why is cellular respiration important?
Cellular respiration produces several vital outcomes which are essential for the maintenance of life. Cellular respiration produces ATP which is the main energy currency for cells, which fuels many biochemical processes which are critical for cellular function. Furthermore, cellular respiration generates carbon dioxide and water as byproducts which are then eliminated from the body to maintain proper pH balance and hydration levels. In addition, the heat which is generated during cellular respiration helps regulate body temperature which ensures optimal conditions for enzymatic activity and metabolic processes. In all the outcomes of cellular respiration plays key roles in sustaining cellular function, supporting growth and maintaining overall physiological homeostasis in living organisms.
Next Articles in The Series
To explore the next parts of the series: Part 2, Part 3, Part 4, Part 5
