CASE FILES: BIOCHEMISTRY
A nsw ers
D. The RBC has no mitochondria so glucose cannot be made from
pyruvate or acetyl-CoA or oxaloacetate. The RBC does have lactate
dehydrogenase and conversion to lactate depends on pyruvate levels.
A. In the RBC a deficiency of pyruvate kinase would tend to shunt
glucose toward the hexose monophosphate pathway increasing ribu-
lose 5-P levels, and the ratio of NADP+ to NADPH would decrease.
NADH to NAD+ ratios would increase as a result of lower pyruvate
levels making more NADH available to reduce methemoglobin and
regenerate NAD+. Because pyruvate kinase is deficient, the last ATP
formation site is compromised, and so is the formation of ATP in the
RBC elevating the ADP to ATP ratio.
C. Glucose to glucose 6-phosphate ^ fructose 6-phosphate ^ fruc-
tose 1,6-bisphosphate ^ glyceraldehyde 3-phosphate ^ 1,3-
bisphosphoglycerate ^ 3-phosphoglycerate ^ 2-phosphoglycerate ^
phosphoenolphosphate ^ pyruvate.
B IO C H E M IS T R Y PE A R L S
The enzyme endowment present at maturation of the RBC cannot be
replaced, and only the glycolytic pathway (Embden-Meyerhof
pathway) is available for energy production in the RBC.
Glucose metabolism is required in the RBC to maintain the ionic
milieu within the cell, the vast majority via conversion to lactate.
The vast majority of RBC enzyme deficiencies involve either altered
protein or decreased protein levels of pyruvate kinase.
Insufficient pyruvate kinase activity compromises erythrocyte ATP
production, leading to ionic imbalance and misshaped cell mem-
branes. These cells are removed from the circulation by the
macrophages of the spleen.
Pyruvate kinase catalyzes one of the three irreversible steps in the
glycolytic pathway, the others being the phosphorylation of glu-
cose to glucose 6-phosphate and the phosphorylation of fructose
6-phosphate to fructose 2,6-bisphosphate.
Braunwald E, Fauci AS, Kasper KL, et al., eds. Harrison’s Principles of Internal
Medicine, 15th ed. New York: McGraw-Hill, 2001.