D efinitions
Hemolytic anemia: A pathologic condition in which there is an abnormally
lowered number of circulating RBCs caused by rupture of RBCs as a
result of membrane abnormalities or deficient enzyme(s) level within the
red blood cell.
Glucose 6-phosphate dehydrogenase: The enzyme that catalyzes the rate
regulating step of the hexose monophosphate shunt, which produces
NADPH required for inactivating oxygen radicals and thereby protects
the RBC membrane from radical attack and rupture.
Pyruvate kinase: Last ATP-producing step in glycolysis and critical in the
RBC for maintaining energy supply (ATP levels).
Methemoglobin reductase: Red blood cell enzyme that uses nicotinamide
adenine dinucleotide (NADH) to convert the iron of oxidized hemoglo-
bin (methemoglobin) from the ferric (Fe3+) to reduced ferrous state
(Fe2+) hemoglobin, which alone is capable of binding O2.
Hemolytic anemia has many causes, though this case has the marks of under-
supply of RBCs caused by an enzyme deficiency within the RBC rather than
a membrane abnormality or an environmental factor such as an autoantibody
or mechanical trauma.
The RBC in the course of its maturation loses its mitochondria, ribosomes, and
nucleus and consequently the functions associated with those organelles such as
new enzyme synthesis and mitochondrial energy formation. Thus the enzyme
endowment present at maturation of the RBC cannot be replaced. In terms
of energy production in the RBC, only the glycolytic pathway (Embden-
Meyerhof pathway) is available. This pathway together with the hexose
monophosphate shunt (pentose phosphate pathway) is shown in Figure 23-1 as
the only metabolic pathways that use glucose in RBCs. As a consequence of
this limited metabolic capacity, glucose is the only fuel usable by the RBC to
generate ATP. Glucose metabolism is required in the RBC to maintain the
ionic milieu within the cell, to maintain the heme cofactor of hemoglobin in
its reduced (Fe2+) state, to maintain reduced sulfhydryl groups, to maintain the
shape of the RBC plasma membrane and to produce 2,3-bisphosphoglycerate,
a modulator of hemoglobin affinity for oxygen. To accomplish these tasks
approximately 90 percent of the glucose in the RBC is metabolized directly to
pyruvate/lactate while approximately 10 percent is first metabolized through
the hexose monophosphate shunt before reentry into the glycolytic pathway.
Approximately 90 percent of all cases of known RBC enzyme deficien-
cies involve either altered protein or decreased protein levels of pyruvate
kinase whereas 4 percent are variants of glucose 6-phosphate isomerase,
which converts glucose 6-phosphate to fructose 6-phosphate. Most of these
enzyme deficiencies are inherited in an autosomal recessive pattern.
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