Corrected 2023 Lec 22 Hemoglobin and oxygen transport PDF

Lecture 22 Hemoglobin and oxygen transport BChD I HUB 105 2023 Dept. Medical Biosciences University of the Western Cape Introduction The resting body requires 250ml of O2 per minute. A small % of O2 is dissolved in plasma, the majority of O2 is carried in the bloodstr...

Lecture 22 Hemoglobin and oxygen transport BChD I HUB 105 2023 Dept. Medical Biosciences University of the Western Cape Introduction The resting body requires 250ml of O2 per minute. A small % of O2 is dissolved in plasma, the majority of O2 is carried in the bloodstream by the Hb in the RBC. 1 RBC = 280mil mol of Hb, each Hb has 4 sites for O2 = billion mol of O2 can be carried. Hb is responsible for the cells ability to transport both O2 and CO2. Normal hemoglobin (adult male): 14–18 g/dL (grams per deciliter (100ml) of whole blood Normal hemoglobin (adult female): 12–16 g/dL whole blood Hb structure β chain 1 α chain 1 β chain 2 Heme Heme α chain 2 Hemoglobin molecule Hb mol is a complex quaternary structure. Composed of globular protein: 2 alpha chains (subunits) and 2 beta chains (subunits) Each Hb chain contains a single mol of heme , a pigment complex. Each heme unit holds a mol of iron ion, that can interact with O2. Iron-O2 interaction is weak and the two can easily dissociate, without deforming heme unit or O2, thus reversible. CO2 and O2 bind to different sites on the Hb protein. Hb Functioning Hb saturation is the amount of oxygen bound to each molecule of hemoglobin which depends on the levels of O2 available in plasma. Each molecule of Hb can carry four molecules of O2. Hb bounded with O2 – oxyhemoglobin (when PO2 level high Hb binds O2) Hb without O2 – deoxyhemoglobin (when PO2 levels low release O2) Occurs in tissues, leads to PCO2 levels elevated and Hb binds to CO2 = HbCO2. Hb role is to bind O2 in lungs and release in tissues; and bind CO2 in tissues and release in the lungs. Oxygen-hemoglobin Dissociation Curve In the lungs the partial pressure for O2 is approximately 100mm Hg at this Partial Pressure hemoglobin has a high affinity to 02 and is 98% saturated. In the tissues of other organs a typical PO2 is 40 mmHg here hemoglobin has a lower affinity for O2 and releases some but not all of its O2 to the tissues. When Hb leaves the tissues it is still 75% saturated. Reserve imp. if tissue Graph reveals the amount of demands for O2 inc. hemoglobin saturation at different PO2 values. Factors Affecting Hemoglobin Saturation  PO of blood plays a small role 2  Blood pH (Normal bld pH 7.4)  Temperature (370 C)  PCO2  Metabolic activity within RBCs generates 2,3 BPG Active tissue consume O2 at an accelerated rate, PO2 drops 15-20mmHg This saturation relationship is shown in the O2-Hb dissociation curve for normal blood. However the factors above when increased or decrease can shift that curve to the right or left, which indicates Hb decrease affinity to O2 or increased affinity to O2, respectively. These factors affect the gas carrying capacity of Hb, by altering its shape which results in the release of the gases or loading of gases. Factors Affecting Hemoglobin Saturation Example: Vigorous physical exercise  Contracting muscles produce metabolic acids such as lactic acid which dec. pH, more heat produced and inc CO2  In addition inc. 2,3 BPG production during conditions of higher temperature and lower PO2  Acting together or individually, these conditions lead to a decrease in Hemoglobin’s affinity for Oxygen, releasing more Oxygen to the tissues (muscles)  Causing the curve in the graph above to shift to the right. Factors Affecting Hemoglobin Saturation Hemoglobin and pH Decrease pH ∴ affinity of Hb for O2 decreases Increase unloading of O2 to tissues Shifts curve to right Increase pH ∴ Hb affinity for O2 increases Shifts curve to the left Hemoglobin and PCO2 Increase PCO2 ∴ Hb affinity for O2 decreases Shifts curve to right Decrease PCO2 ∴ Hb affinity Increase and holds onto O2 Shift curve to the left - Shifts curve to right, thus at every level of PO2, more O2 gets released than normal - Shift curve to the left, thus at every level of PO2, the O2 saturation of Hb is greater than normal Factors Affecting Hemoglobin Saturation Hemoglobin and Temperature Temp increase ∴ Hb affinity for O2 decreases Shifts the curve to right Temp decrease ∴ Hb affinity for O2 increases Shifts the curve to the left During hypothermia, more oxygen remains bound to Hb Temp. effects are significant only in active tissues that are generating large amounts of heat – For example, active skeletal muscles Factors Affecting Hemoglobin Saturation 2,3-BPG (bisphosphoglycerate) BPG formed by RBC during glycolysis Effect of 2,3-DPG (BPG) which forms lactic acid and BPG BPG directly affects O2 binding and release Helps release O2 by binding with Hb itself BPG increase ∴ Hb affinity for O2 decreases, release to tissue and BPG binds to Hb. Shifts curve to the right BPG decrease ∴ Hb affinity for O2 increases Shifts curve to the left Factors Affecting Hemoglobin Saturation Shifts in O2-HB dissociation curve  Shift curve to right, thus at every level of PO2, more O2 gets released than normal – advantage: in the tissues where more O2, is released – disadvantage: in the lungs because blood takes up less oxygen  Shift curve to the left, thus at every level of PO2, the O2 saturation of Hb is greater than normal – advantage: limited, but does allow greater uptake of O2 in the lungs – disadvantage: decrease the release of O2 at the tissues Factors Affecting Hemoglobin Saturation Carbon Monoxide (CO) CO is produced endogenously in small amounts thru heme catabolism and assist in cellular function and acts as a neurotransmitter. Environmental CO is produced burning fuels, car exhaust , oil lamps and natural gases Silent killer no smell or colour. CO has a 210 times stronger affinity for Hb than oxygen. CO and O2 compete for binding site on Hb as it binds to the same site. Cellular uptake of O2 is blocked when Hb bound to CO forming Carboxyhemoglobin (HbCO) This affinity of CO for Hb shifts the O2-Hb curve to the left, reducing the ability to release O2 at the tissue level. Can result in carbon monoxide poisoning Carbon monoxide shifts the oxygen- haemoglobin saturation curve to the left. Less oxygen is available for the tissues. Revision Questions: 1. Define following: Hb saturation, O2-Hb dissociation curve 2. Name the functions of Hb. 3. Explain the O2-Hb dissociation curve at normal pH and body temperature. 4. Describe the structure of Hb. 5. Name the factors involved in the Hb saturation of 02. 6. How do these factors affect the affinity of Hb for O2. 7. Why is CO dangerous for humans.