Red Cell Metabolism

Because the mature red cell is an anucleate structure, it has no nuclear or mitochondrial architecture for metabolizing fatty or amino acids. Consequently, it derives all of its energy from the breakdown of glucose. Within this framework, the red cell must maintain its shape, keep hemoglobin in the reduced (Fe2+) state, and move electrolytes across the membrane. There are three metabolic pathways that are essential for red cell function, as follows:

1. The Embden-Meyerhof pathway provides 90% of the cellular ATP because red cell metabolism is essentially anaerobic. The functions of ATP are multifactorial and include maintenance of membrane integrity, regulation of the intracel-lular and extracellular pumps, maintenance of hemoglobin function, and replacement of membrane lipids.5 This pathway also generates NAD+ from NADH, an important structure in the formation of 2,3-diphosphoglycerate, a key element to oxygen loading and unloading.

2. The hexose monophosphate shunt provides 5% to 10% of the ATP necessary so that NADPH is produced and globin chains will not be degraded when subjected to oxidative stress and the accumulation of hydrogen peroxide. If this pathway is deficient, globin chains may precipitate, forming Heinz body inclusions in the red cell. Heinz body inclusions will lead to the formation of bite cells in the peripheral blood as Heinz bodies are pitted from the cell by the spleen.

3. The methemoglobin reductase pathway, which maintains hemoglobin iron in the reduced ferrous state, Fe2+, so that oxygen can be delivered to the tissues, is dependent on the reduction of NAD to NADPH (Fig. 3.9). If this enzyme is absent, methemoglobin accumulates in the red cells. Oxygen transport capabilities are seriously impaired because methemoglobin cannot combine with oxygen.

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