Cellular respiration is the process by which cells in the human body convert nutrients into energy in the form of ATP (adenosine triphosphate). This metabolic process is essential for providing energy for all cellular activities. The main source of energy for cellular respiration is the sugar glucose.
What is cellular respiration?
Cellular respiration is a series of metabolic reactions that take place in the cells of organisms to convert biochemical energy from nutrients into ATP. There are three main stages of cellular respiration:
- Glycolysis – Glucose is broken down into pyruvate in the cytoplasm, producing a small amount of ATP and NADH.
- Krebs Cycle – Pyruvate enters the mitochondria and goes through a cycle of reactions that produce NADH, FADH2, and CO2.
- Oxidative phosphorylation – NADH and FADH2 donate electrons to the electron transport chain on the inner mitochondrial membrane, which drives protons across this membrane to generate ATP.
The overall equation for cellular respiration is:
C6H12O6 (glucose) + 6O2 → 6CO2 + 6H2O + energy (ATP)
So glucose and oxygen are consumed, and carbon dioxide, water, and energy are produced.
Why is glucose the main source of energy?
Glucose is the preferred source of energy in the human body because:
- It is relatively small and soluble in water, so it can easily enter and move through cells.
- Many foods are broken down into glucose during digestion, providing a readily available source.
- Glucose is the end product of photosynthesis in plants and is therefore abundant in nature.
- Cells can break glucose down through glycolysis in the absence of oxygen.
- The breakdown of glucose provides the most energy per molecule – each molecule produces about 30-32 ATP.
Glucose is stored in the body as glycogen in liver and muscle cells. When needed for energy, glycogen is quickly broken down into glucose. Blood glucose levels are strictly regulated by hormones like insulin and glucagon to ensure a steady supply of fuel for cells.
Glycolysis – Breakdown of Glucose
Glycolysis is the first stage of cellular respiration and takes place in the cytoplasm of cells. In this process glucose is split into two three-carbon molecules called pyruvate. This metabolic pathway does not require oxygen and produces a net gain of 2 ATP and 2 NADH molecules per glucose molecule.
The ten step process of glycolysis is summarized below:
- Glucose is phosphorylated by hexokinase to form glucose-6-phosphate.
- Glucose-6-phosphate is converted to fructose 6-phosphate by phosphoglucose isomerase.
- Phosphofructokinase-1 phosphorylates fructose 6-phosphate to make fructose 1,6-bisphosphate, using one ATP.
- Aldolase splits fructose 1,6-bisphosphate into two three-carbon molecules, glyceraldehyde 3-phosphate and dihydroxyacetone phosphate.
- Triose phosphate isomerase converts dihydroxyacetone phosphate to a second glyceraldehyde 3-phosphate molecule.
- Glyceraldehyde 3-phosphate is oxidized and phosphorylated by glyceraldehyde 3-phosphate dehydrogenase, forming 1,3-bisphosphoglycerate and producing the first NADH molecule.
- Phosphoglycerate kinase catalyzes the transfer of a phosphate from 1,3-bisphosphoglycerate to ADP, forming one ATP molecule.
- Phosphoglycerate mutase converts 3-phosphoglycerate to 2-phosphoglycerate.
- Enolase converts 2-phosphoglycerate to phosphoenolpyruvate (PEP).
- Pyruvate kinase transfers a phosphate from PEP to ADP, forming another ATP molecule and the end product pyruvate.
So in summary, each molecule of glucose is broken down into two pyruvate molecules, producing a net gain of 2 ATP and 2 NADH during glycolysis. This provides a small amount of energy for the cell to use.
Krebs Cycle
The pyruvate generated during glycolysis enters the mitochondria and undergoes further oxidation in the Krebs cycle, also known as the citric acid cycle or tricarboxylic acid (TCA) cycle. This cycle produces high-energy molecules NADH and FADH2 that will be used in the next phase of respiration.
In the Krebs cycle:
- Pyruvate is converted to acetyl coenzyme A (acetyl CoA).
- Acetyl CoA enters the cycle by reacting with oxaloacetate to form citrate.
- Citrate undergoes a series of chemical modifications, converting back to oxaloacetate.
- In the process, 3 NADH, 1 FADH2, and 1 ATP (by substrate-level phosphorylation) are produced per acetyl CoA entering the cycle.
- Since two acetyl CoA were derived from each glucose molecule, the Krebs cycle produces a net gain of 2 ATP, 6 NADH and 2 FADH2 per glucose.
The Krebs cycle oxidizes the glucose derivative acetyl CoA completely to carbon dioxide and water. The energy released is captured in the NADH and FADH2 molecules, which will be used to power oxidative phosphorylation and generate more ATP.
Oxidative Phosphorylation
Oxidative phosphorylation is the final stage of cellular respiration and occurs in the inner mitochondrial membrane. It produces the majority of the ATP. NADH and FADH2 carry electrons from the Krebs cycle to the electron transport chain, passing these electrons through a series of proteins.
The electron transport chain:
- Accepts electrons from NADH and FADH2.
- Passes electrons down the chain of proteins/complexes in the inner membrane.
- Allows protons to move across the membrane from the matrix to the intermembrane space, forming an electrochemical proton gradient.
- The protons flow back into the matrix through ATP synthase, which uses the proton-motive force to produce ATP from ADP and inorganic phosphate.
The entire electron transport chain, called the respiratory chain, produces about 30-32 ATP for every molecule of glucose that enters cellular respiration. This makes up over 90% of the total ATP generated.
Net ATP Production
Adding up the ATP produced in all three stages of cellular respiration:
- Glycolysis produces 2 ATP and 2 NADH per glucose.
- Krebs cycle produces 2 ATP, 6 NADH and 2 FADH2 per glucose.
- Oxidative phosphorylation produces ~30-32 ATP per glucose using the NADH and FADH2.
The total net production is approximately 30-36 ATP per molecule of glucose used. This efficiently extracts energy from glucose to power cellular activities.
Other Respiratory Substrates
While glucose is the preferred fuel source, other molecules can also be used as respiratory substrates and fed into cellular respiration:
- Fats/Fatty acids – Broken down through beta-oxidation into acetyl CoA, which enters the Krebs cycle.
- Amino acids – Deaminated and converted to Krebs cycle intermediates or acetyl CoA.
- Glycerol – From fats/oils, converted to glyceraldehyde-3-phosphate and enters glycolysis.
- Lactate – Converted back to pyruvate and enters the Krebs cycle.
However, glucose remains the primary fuel for cellular respiration in humans and other animals because it is the most readily available source that can be broken down quickly and efficiently to supply energy demands.
Anaerobic Respiration
When oxygen is limited or unavailable, cells can perform anaerobic respiration or fermentation. This consists only of the glycolysis stage, and does not require oxygen to metabolize glucose.
Lactic acid fermentation is common in human muscle cells during intense exercise when oxygen debt occurs. Pyruvate is converted to lactate instead of acetyl CoA. This produces much less ATP – only 2 ATP per glucose compared to 30-32 ATP in aerobic respiration.
Yeast perform ethanol fermentation, converting pyruvate to ethanol and CO2. This is used in brewing and baking.
Anaerobic respiration does not require oxygen but produces far less ATP. It enables cells to survive temporary oxygen shortages. Aerobic respiration is much more efficient for producing energy.
Regulation of Cellular Respiration
To ensure cellular respiration provides energy at a rate matching demand, the pathways are finely controlled by a number of mechanisms:
- Allosteric regulation – Regulatory molecules bind to enzymes in glycolysis and the Krebs cycle to increase/decrease their activity.
- Substrate availability – Key substrates like glucose and fatty acids are maintained at consistent levels through hormones.
- Inhibitors – Molecules like ATP and NADH inhibit enzymes to slow down pathways when their levels get too high.
- Mitochondria numbers – Cells can increase mitochondria to ramp up energy production.
These controls allow cells to tightly regulate cellular respiration and match the supply of ATP to the fluctuating energy demands.
Defects in Cellular Respiration
Errors or deficiencies in cellular respiration enzymes or complexes can impair energy production and cause medical conditions:
| Condition | Description |
|---|---|
| Lactic acidosis | Buildup of lactate from impaired pyruvate metabolism, causing acidosis. |
| Pyruvate dehydrogenase deficiency | Impaired conversion of pyruvate to acetyl CoA. |
| Respiratory chain defects | Mutations affecting complexes in the electron transport chain. |
| Mitochondrial myopathy | Muscle weakness from mitochondrial defects. |
These conditions affecting cellular respiration can have serious consequences but are fortunately rare due to the essential nature of this metabolic process.
Conclusion
In summary, the main source of energy for cellular respiration in humans and other animals is the sugar glucose. Glucose is metabolized through the glycolysis pathway, Krebs cycle, and oxidative phosphorylation to generate approximately 30-32 molecules of ATP per glucose molecule.
This efficient extraction of energy from nutrients makes glucose the ideal respiratory substrate to fuel the cells of the body. Cellular respiration is tightly regulated to supply energy on demand and defects in this essential process can lead to detrimental medical conditions.
