A 3-year-old boy was found to have reduced red blood cell (RBC) numbers yet exhibited very few signs of anemia. An analysis of labeled RBCs indicated a greatly reduced ATP yield as compared to someone without the anemia. In this child, which one of the following would be expected to increase in RBC?
Function of Hb. Hb, found in the red blood cells, carries oxygen from the lungs to the tissues and returns carbon dioxide and protons from the tissues to the lungs.a. The oxygen saturation curve for Hb is sigmoidal (Figure I).(1). Each heme binds one O2 molecule, for a total of four O2 molecules per HbA molecule. HbA changes from the taut or tense (T) form to the relaxed (R) form when oxygen binds.(2). Binding of O2 to one heme group in Hb increases the affinity for O2 of its other heme groups. This effect produces the sigmoidal oxygen saturation curve and is known as positive cooperativity.b. The binding of protons to HbA stimulates the release of O2 , a manifestation of the Bohr effect (see Figure I).(1). Thus, O2 is readily released in the tissues where is high because of the production of CO2 by metabolic processes.(2). These reactions are reversed in the lungs. O2 binds to HbA, and CO2 is exhaled (see Figure II).c. Covalent binding of CO2 to HbA in the tissues also causes the release of O2 .d. Binding of 2,3-bisphosphoglycerate (BPG), a side product of glycolysis in red blood cells, decreases the affinity of HbA for O2 . Consequently, O2 is more readily released in tissues when BPG is bound to HbA (see Figure I).e. Fetal hemoglobin (HbF), composed of two a subunits and two g subunits, has a lower affinity for BPG than does HbA, and therefore, HbF has a higher affinity for O2 than does HbA.The child has an inherited pyruvate kinase deficiency. This step converts phosphoenolpyruvate (PEP) to pyruvate, thereby producing ATP. A pyruvate kinase deficiency would slow down glycolysis, and less ATP would be produced. As PEP accumulates, so does 2-PG, 3-PG, and 1,3-BPG. The Luebering-Rapoport shunt converts 1,3-BPG to 2,3-BPG (via bisphosphoglycerate mutase), which aids in releasing oxygen from hemoglobin in the tissues. The other intermediates of glycolysis before the blocked step would accumulate, and glucose-6-phosphate would inhibit hexokinase. Because of a lack of ATP, the life span of the cells would decrease. Fatty acids cannot serve as a source of energy because RBCs lack mitochondria, which is the site of fatty acid oxidation.I. Oxygen saturation curves for myoglobin and adult hemoglobin (HbA). Myoglobin has a hyperbolic saturation curve. HbA has a sigmoidal curve. The HbA curve shifts to the right at lower pH, with higher concentrations of BPG, or as CO2 binds to HbA in the tissues. Under these conditions, O2 is released more readily. P50 is the partial pressure of O2 at which half-saturation with O2 occurs. BPG, 2,3-bisphosphoglycerate.II. Effect of H+ on oxygen binding by hemoglobin (Hb). A. In the tissues, CO2 is released. In the red blood cells, this CO2 forms carbonic acid, which releases protons. The protons bind to Hb, causing it to release oxygen to the tissues. B. In the lungs, the reactions are reversed. O2 binds to protonated Hb, causing the release of protons. The protons bind to bicarbonate, forming carbonic acid, which is cleaved to water and CO2 , which is exhaled. RBC, red blood cell
The life span of the RBCs
The rate of fatty acid oxidation
ATP production
The levels of 2,3-bisphosphoglycerate
Carbohydrates