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Hematological anomalies have been observed in patients with prolonged liver damage. For example, patients with chronic cirrhosis (scarring of the liver) often develop anemia and other blood disorders. Hemoglobin is the metalloprotein within red blood cells that is responsible for the oxygen-carrying capacity of blood, and its function may be affected by liver damage. The poor prognosis of patients with cirrhosis and anemia has stimulated further study of hemoglobin function and oxygen saturation.Blood samples from both cirrhotic patients and healthy individuals at rest and after exercise were exposed to varying partial pressures of oxygen. Measurement of oxyhemoglobin dissociation curves (ODCs [Figure 1]) from the blood samples revealed significant functional differences in the hemoglobin from cirrhotic patients relative to control subjects.
Figure 1 Oxyhemoglobin dissociation curve for cirrhotic patients (CP) at rest and for healthy controls (HC) at rest and after 20 minutes of exerciseVitamins are considered nontoxic supplements and are frequently provided to anemic patients to increase red blood cell production. They may therefore have therapeutic benefits for cirrhotic patients. However, some studies indicate that excessive vitamin consumption may lead to oxidative stress that could induce anemia through hemolysis (red blood cell rupturing) . Hemoglobin strongly absorbs light at 577 nm, and researchers conducted hemolysis assays by spinning down red blood cells and measuring absorbance (Abs) of the supernatant at 577 nm to determine how much hemoglobin was released. The assay was carried out in the presence of four vitamins to determine their potential as oxidizing agents, and results are shown in Table 1.Table 1 Hemolysis of Red Blood Cells from Healthy Donors Treated With Vitamins [2 mM] for 30 Minutes, Measured by Absorbance at 577 nm
Adapted from Clerbaux T, Detry B, Geubel A, et al. The oxyhemoglobin dissociation curve in liver cirrhosis. Chest. 2006;129(2) :438-45.
-Upregulation of which enzyme could improve oxygen release into the tissues of cirrhotic patients?

Question

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Hematological anomalies have been observed in patients with prolonged liver damage. For example, patients with chronic cirrhosis (scarring of the liver) often develop anemia and other blood disorders. Hemoglobin is the metalloprotein within red blood cells that is responsible for the oxygen-carrying capacity of blood, and its function may be affected by liver damage. The poor prognosis of patients with cirrhosis and anemia has stimulated further study of hemoglobin function and oxygen saturation.Blood samples from both cirrhotic patients and healthy individuals at rest and after exercise were exposed to varying partial pressures of oxygen. Measurement of oxyhemoglobin dissociation curves (ODCs [Figure 1]) from the blood samples revealed significant functional differences in the hemoglobin from cirrhotic patients relative to control subjects.

Figure 1 Oxyhemoglobin dissociation curve for cirrhotic patients (CP) at rest and for healthy controls (HC) at rest and after 20 minutes of exerciseVitamins are considered nontoxic supplements and are frequently provided to anemic patients to increase red blood cell production. They may therefore have therapeutic benefits for cirrhotic patients. However, some studies indicate that excessive vitamin consumption may lead to oxidative stress that could induce anemia through hemolysis (red blood cell rupturing) . Hemoglobin strongly absorbs light at 577 nm, and researchers conducted hemolysis assays by spinning down red blood cells and measuring absorbance (Abs) of the supernatant at 577 nm to determine how much hemoglobin was released. The assay was carried out in the presence of four vitamins to determine their potential as oxidizing agents, and results are shown in Table 1.Table 1 Hemolysis of Red Blood Cells from Healthy Donors Treated With Vitamins [2 mM] for 30 Minutes, Measured by Absorbance at 577 nm

Adapted from Clerbaux T, Detry B, Geubel A, et al. The oxyhemoglobin dissociation curve in liver cirrhosis. Chest. 2006;129(2) :438-45.
-Upregulation of which enzyme could improve oxygen release into the tissues of cirrhotic patients?

Quizplus · Accepted Answer

11ecba2d_0f59_ca97_a3bf_654f22799799_MD0008_00 Hemoglobin's affinity for oxygen is decreased in the presence of 2,3-bisphosphoglycerate (2,3-BPG) within the red blood cell. 2,3-BPG binds hemoglobin at an allosteric site and stabilizes the deoxygenated conformation. This reduces oxygen binding and increases O₂ release into tissues (right shift on oxygen dissociation curve). Therefore upregulation of an enzyme that produces 2,3-BPG could improve oxygen release. Mutases facilitate reactions that change the location of a functional group within a molecule. The enzyme bisphosphoglycerate mutase converts 1,3-BPG to 2,3-BPG by transferring a phosphate from carbon 1 to carbon 2 within a bisphosphoglycerate molecule. Upregulation of this enzyme would therefore increase the concentration of 2,3-BPG and could facilitate oxygen release into the tissues of cirrhotic patients. (Choice A) Kinases add and, in some cases, remove phosphate groups. Phosphoglycerate kinase interconverts 1,3-bisphosphoglycerate and 3-phosphoglycerate and is not involved in production of 2,3-BPG. (Choice B) Glyceraldehyde-3-phosphate dehydrogenase converts glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate (1,3-BPG). It is not involved in oxygen release by hemoglobin. (Choice D) Although phosphoglycerate mutase does have mutase activity, it interconverts 3-phosphoglycerate and 2-phosphoglycerate. It acts on phosphoglycerates, not bisphosphoglycerates. Educational objective: Bisphosphoglycerate mutase converts 1,3-bisphosphoglycerate into 2,3-bisphosphoglycerate, which allosterically regulates hemoglobin. It decreases oxygen affinity by stabilizing the deoxyhemoglobin conformation. Increasing concentrations of 2,3-bisphosphoglycerate produce a right shift in the oxyhemoglobin dissociation curve and favor oxygen delivery to tissues.

Passage Hematological Anomalies Have Been Observed in Patients with Prolonged Liver