How Fitness Impacts Hemoglobin’s O2 Affinity and Its Structure

Hemoglobin (4 colored pipecleaers with 4 white pom poms as heme) in T state, with CO₂ (blue pom poms) bound to the globin proteins. In an environment with lots of O₂ (red pom poms), such as the lungs. Hemoglobin will unload CO₂ to be expired, and take on O₂ to transport around the body.

Hemoglobin (4 colored pipecleaers with 4 white pom poms as heme) in R state, with O₂ (red pom poms) bound to the heme groups. In an environment with lots of CO₂ (blue pom poms), such as the tissues. Hemoglobin will unload O₂ to the tissues and transition back to the T state, and take on some CO₂ to transport back to the lungs.

Molecular oxygen is an essential compound required for survival and energy production. Usually, when people think of oxygen (O₂), they think of the lungs because that is where oxygen enters the body. However, blood is the key player when it comes to transporting oxygen throughout the body. Hemoglobin, a protein structure found in high numbers on each erythrocyte (Betts et al., 2022), is capable of binding to O₂, which effectively transports oxygen throughout the body. The process by which hemoglobin binds and releases oxygen is not fixed, as an individual’s fitness level can impact how efficiently this process works. Endurance training and regular exercise help the body improve oxygen delivery, especially when undergoing physical activity (Böning et al., 1975). Understanding how hemoglobin functions to bind and deliver O₂ is crucial for understanding the overall health benefits of staying in shape. Since the structure of hemoglobin changes as O₂ and carbon dioxide (CO₂) bind to it, using a 3-D model is a good way of showing the structural changes. 

In places where the partial pressure of oxygen (PO₂) is high, such as the lungs, the high concentrations force hemoglobin to unload CO₂ and transition into a tight (T) state (Larson, 2026). This transition between T and relaxed (R) structures is dependent on the partial pressures of O₂ and CO₂, as well as pH (Mairbäurl, 2013). The binding of oxygen at the lungs is a cooperative process, which means that once one oxygen binds to hemoglobin and transitions it to an R state, more oxygen binds easily. In tissues, there are low concentrations of O₂ and low pH and CO₂ concentrations, as CO₂ is produced as a result of cellular metabolism. Lower pH means more H⁺ ions, which decreases hemoglobin’s affinity for O₂, which means O₂ is unloaded at the tissues (Mairbäurl, 2013). Delivering oxygen to working tissues is important, since they are expending more energy. When exercising, the pH and pCO₂ at the tissues shift to favor oxygen release to maintain proper cellular function. This means that regular exercise can create more efficient oxygen transport, since the rate of O₂ release is largely reliant on the efficiency of the transport (Böning et al., 1975). 

Fitness and endurance training alter how hemoglobin interacts with O₂ by shifting the oxygen dissociation curve (Hemoglobin % saturation vs PO₂ of blood) to the right. People who are more fit present with this right shift, which means hemoglobin releases oxygen more easily at the tissues (Mairbäurl, 2013). Besides just the body requiring more O₂ at the tissues during exercise, which can train the body to be more efficient with loading and unloading O₂ if done consistently, exercise increases the concentration of 2,3-disphosphoglycerate (2,3-DPG) in erythrocytes. Böning et al.’s paper found that fit people have around 15-20% more 2,3-DPG than untrained individuals, and that difference can cause a difference in the PO₂ of around 2 mmHg! 2,3-DPG further reduces hemoglobin’s affinity for oxygen, which means more O₂ can be delivered to the tissues. Beyond chemical changes with exercise, regular training increases total blood volume and erythrocyte flexibility, which means more O₂ can be delivered more easily (Mairbäurl, 2013). Exercise also increases capillary density, which means there are more vessels available to carry blood (and therefore O₂) to the tissues (Mairbäurl, 2013). These two non-molecular changes, combined with the molecular changes to hemoglobin, improve oxygen supply throughout the body. This means that people who exercise regularly, especially endurance training, perform better physically because of how efficiently their bodies transport oxygen (Böning et al., 1975). 

My STEAM projects show how hemoglobin changes shape under various conditions. The pipecleaners represent the four protein groups (globins) that make up hemoglobin. The white pom poms on the pipecleaners represent the heme pigment, which contains Fe²⁺, that is responsible for binding to O₂ (Larson, 2026). Red pom poms represent O₂, while blue pom poms represent CO₂. Two states of hemoglobin are shown: one where CO₂ is bound to the globin strands, which puts hemoglobin in a tight state, and another where O₂ is bound to hemoglobin, which puts it into a relaxed state. Each of these states is shown in a situation where it would start to transition into a different state by unloading the compounds currently bound to it. This means the T state hemoglobin is in high PO₂ conditions, which means CO₂ would be unloaded to take up the excess O₂ found in the lungs. The R state hemoglobin is in high PCO₂ conditions, which means the bound O₂ would begin to be released to distribute oxygen to the tissues. 

In conclusion, studies have found that fitness is a definitive factor in improving how oxygen is carried throughout the body. Some changes that some with fitness include improved erythrocyte function, a right shift in the oxygen dissociation curve, increased 2,3-DPG concentrations, and increased situations where efficient O₂ transport is required. These changes allow the body to handle the demands of physical activity better than someone who does not exercise. The pipecleaner and pom pom diagram shows the details of how oxygen is transported within the blood, which is made more efficient with regular exercise. 

References

Betts, J. G., Young, K. A., Wise, J. A., Johnson, E., Poe, B., Kruse, D. H., Korol, O., Johnson, J. E., Womble, M., & DeSaix, P. (2022, April 20). Erythrocytes. In Anatomy and physiology 2e. OpenStax. https://openstax.org/books/anatomy-and-physiology-2e/pages/18-3-erythrocytes. 

Böning, D., Schwiegart, U., Tibes, U., & Hemmer, B. (1975). Influences of exercise and endurance training on the oxygen dissociation curve of blood under in vivo and in vitro conditions. European Journal of Applied Physiology and Occupational Physiology, 34(1), 1–10. https://doi.org/10.1007/BF00999910. 

Larson, D. (2026). Unit 11: Cardiovascular system [PowerPoint slides]. University of Alaska Fairbanks, Canvas. https://canvas.alaska.edu/courses/28673/pages/unit-11-lecture-notes?module_item_id=1435797. Mairbäurl, H. (2013, November 12). Red blood cells in sports: Effects of exercise and training on oxygen supply by red blood cells. Frontiers in Physiology, 4, 332. https://doi.org/10.3389/fphys.2013.00332.