Which one of the following combinations is NOT correct?
(1) A and B (2) B and C
(3) C and D (4) D and E

Red blood cells (RBCs) are unique among human cells due to their specialized structure and metabolic profile. Lacking nuclei and mitochondria, RBCs rely on specific metabolic pathways to maintain their function and integrity. Understanding these pathways is essential for grasping RBC physiology and pathology.

This article evaluates several statements about RBC metabolism to determine which combinations are not correct.

Overview of Metabolic Features in RBCs

A. Fatty Acid Synthesis in RBCs

• RBCs do not synthesize fatty acids.

• Their membranes contain lipids, but these are maintained and remodeled rather than synthesized de novo.

• Fatty acid synthesis primarily occurs in the liver and adipose tissue, not in mature RBCs.

B. Pentose Phosphate Pathway (PPP) in RBCs

• The pentose phosphate pathway is active in RBCs.

• It generates NADPH, which is critical for maintaining glutathione in its reduced form (GSH), protecting RBCs from oxidative damage.

• PPP also produces ribose-5-phosphate for nucleotide synthesis, although RBCs lack nuclei and do not replicate DNA.

C. Glutathione Synthesis in RBCs

• RBCs cannot synthesize glutathione de novo because they lack the enzymatic machinery for its synthesis.

• Instead, RBCs import glutathione precursors and maintain glutathione in its reduced state via NADPH-dependent glutathione reductase.

• Reduced glutathione (GSH) is vital for neutralizing reactive oxygen species.

D. Presence of Enzymes like Adenosine Deaminase and Pyrimidine Nucleotidase

• RBCs contain enzymes such as adenosine deaminase and pyrimidine nucleotidase.

• These enzymes are involved in nucleotide metabolism and turnover, important for maintaining nucleotide pools and preventing accumulation of toxic metabolites.

• Deficiencies in these enzymes can lead to hemolytic anemia.

E. NADH-Dependent Methemoglobin Reductase System in RBCs

• RBCs possess the NADH-dependent methemoglobin reductase system.

• This enzyme system reduces methemoglobin (oxidized hemoglobin) back to functional hemoglobin, maintaining oxygen transport capacity.

• It uses NADH generated from glycolysis as a cofactor.

Evaluating the Combinations for Incorrectness

Conclusion

The combination that is NOT correct is:

(3) C and D

• While statement C is true (RBCs cannot synthesize glutathione), statement D is false because RBCs do contain enzymes like adenosine deaminase and pyrimidine nucleotidase.