Metabolism of Red Blood Cells: MCQ

Which of the following is a FALSE statement about the fate of the glycolytic pathway in erythrocytes?
a) Glycolysis is the sole source of ATP in erythrocytes.
b) Deficiency of pyruvate kinase leads to hemolytic anemia.
c) Pyruvate generated during glycolysis is converted to lactate.
d) Pyruvate generated during glycolysis is converted to acetyl CoA and enters the TCA cycle in mitochondria.

(Correct Answer: Please find it at the end of this text)

The objective of the MCQ above is to discuss
- Shape and morphology of Red blood cell
- The fate of glucose in red blood cells
- Metabolic control of glucose metabolism

  • Red blood cells are bone marrow-derived non-dividing cells that contain hemoglobin (95% of intracellular protein) and help to transport oxygen from the lungs to peripheral tissue. 
  • The RBCs help in the disposal of carbon dioxide and a proton from the peripheral tissue, they are biconcave in the structure, this type of structure increases the surface-to-volume ratio and facilitates gas exchange. 
  • Morphologically, red blood cells are anucleated and lack organelles such as mitochondria, lysosomes, or Golgi apparatus. 

Although biosynthetic pathways do not occur in RBC, ATP, and NADPH are required for the maintenance of cellular structure The energy is utilized by anion-exchange proteins, NA+ K+ ATPase, other transporter proteins to maintain cellular homeostasis. The glycolytic pathway occurs in cytosol and pyruvate can be converted to lactate and regenerate the NAD required for the continuation of the glycolytic pathway. These characteristics of the glycolytic pathway make glucose which is a suitable source of energy in red blood cells.

In red blood cells, glucose can into two different pathways;
  • Glycolysis
  • Pentose phosphate pathway
Glycolysis is the conversion of glucose into pyruvate with the generation of net 2 ATPs and 2 NADH. The glycolytic pathway is activated when the cellular ATP level is decreased. These ATPs are utilized by various ion transporter to maintain the integrity of the cells. 
The hemoglobin in red blood cells binds to oxygen and deliver to the target tissues. Auto-oxidation of iron-containing hemoglobin and propagation of electrons leads to a generation of free radicals that are toxic to the tissues. The red blood cell consists of enzymes such as catalase, superoxide dismutase. 
Superoxide dismutase, glutathione requiring enzyme, converts superoxide to hydrogen peroxide and catalase converts hydrogen peroxide into water and oxygen. Superoxide dismutase enzyme activity depends on the availability of reduced glutathione. The glutathione peroxidase catalyzes the cycling of reduced glutathione at an expense of NADPH. 

The pentose phosphate pathway generates NADPH that is utilized by RBC for converting toxic superoxide radicals to non-toxic oxygen and water.

The fate of glucose in red blood cells

Glutathione NADPH cycle in RBC.
SOD- Superoxide dismutase, GSH- Glutathione, GPX-Glutathione peroxidase, G6PD-Glucose-6-phosphate dehydrogenase, CAT- Catalase

The defective enzymes of the glycolytic pathway or pentose phosphate pathway can adversely affect the cellular integrity of red blood cells by two distinct mechanisms. The defect in the glycolytic pathway can lead to decreased ATP production, a decrease in the activity of ATP-dependent ions channels, dysregulation of ions, and cellular lysis. 
On the other hand, the defect in the enzyme of the pentose phosphate pathway (e.g. glucose-6-phosphate dehydrogenase) leads to decreased NADPH, decreased activity of NADPH dependent enzymes, accumulation of toxic free radicals ultimately leading to hemolytic anemia.

Answer D is the correct answer ( Red blood cells lack mitochondrial that is required for the conversion of pyruvate to acetyl CoA)