A 54-year-old man with a history of chronic kidney disease due to hypertension develops anemia. Evaluation reveals that the cause of anemia is erythropoietin deficiency. Erythropoietin increases the numbers of erythroid precursor cells in the bone marrow and induces heme production in erythrocyte precursors. In this patient, mature erythrocytes are found that are unable to synthesize heme even though they contain detectable levels of cytoplasmic enzymes involved in heme synthesis. Lack of which of the following cellular organelles best explains this phenomenon?
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Heme synthesis occurs partly in the mitochondria and partly in the cytoplasm of erythrocytes. Mitochondria are necessary for the first and the final 3 steps. Erythrocyte precursors divide a number of times before finally losing their nuclei and mitochondria and forming mature red blood cells that survive for about 120 days (4 months). When erythrocytes lose their mitochondria, they lose the ability to generate heme and therefore hemoglobin.
Heme is synthesized in virtually every organ, but the principal sites of synthesis are erythrocyte precursor cells (located in the bone marrow) and hepatocytes (use heme in microsomal cytochrome P450 system).
(Choices A, B, and D) Although mature erythrocytes do not contain a nucleus, a Golgi apparatus, or an endoplasmic reticulum, their cytoplasm still contains residual amounts of the enzymes necessary for heme synthesis. Therefore, the lack of mitochondria (and their associated heme biosynthetic enzymes) is a better explanation for the lack of heme synthesis.
(Choices E and F) Proteasomes are involved in protein recycling and peroxisomes are involved in fatty acid catabolism. These organelles typically disappear during erythrocyte development.
Educational objective:
Maturing erythrocytes lose their ability to synthesize heme when they lose their mitochondria, which are necessary for the first and final 3 steps of heme synthesis.