Moestrup SK (2006). New insights into carrier binding and epithelial uptake of the erythropoietic nutrients cobalamin and folate. Curr Opin Hematol. 13(3):119-23.
PURPOSE OF REVIEW: In addition to malnutrition several genetic and acquired conditions may affect the homeostasis of cobalamin (vitamin B12) and folate, leading to large, under-developed red blood cells. The present review describes new insight into protein handling of cobalamin and folate.
RECENT FINDINGS: The recent solution of the three-dimensional structure of the cobalamin binder transcobalamin shows two separate domains enclosing the vitamin. This structure apparently also applies for the other homologous cobalamin binders, intrinsic factor and haptocorrin. Genetic studies of inherited cobalamin malabsorption and biochemical studies have now revealed that the functional receptor for uptake of intrinsic factor-vitamin cobalamin complexes also is a complex itself consisting of two different gene products, cubilin and amnionless. A role in folate uptake of megalin, an endocytic receptor for epithelial uptake of various proteins including transcobalamin, is now also indicated by the observation that megalin can mediate uptake of soluble folate receptor.
SUMMARY: New data show the structure of cobalamin carriers and reveal novel proteins involved in the epithelial uptake of cobalamin and folate. Genetic abnormalities in three different genes encoding proteins in the epithelial uptake of cobalamin are now known to cause malabsorption of cobalamin and large red blood cells.
Koury MJ, Ponka P (2004). New insights into erythropoiesis: the roles of folate, vitamin B12, and iron. Annu Rev Nutr. 24:105-31.
Erythropoiesis is the process in which new erythrocytes are produced. These new erythrocytes replace the oldest erythrocytes (normally about one percent) that are phagocytosed and destroyed each day. Folate, vitamin B12, and iron have crucial roles in erythropoiesis. Erythroblasts require folate and vitamin B12 for proliferation during their differentiation. Deficiency of folate or vitamin B12 inhibits purine and thymidylate syntheses, impairs DNA synthesis, and causes erythroblast apoptosis, resulting in red blood cell deficiencies from ineffective erythropoiesis. Erythroblasts require large amounts of iron for hemoglobin synthesis. Large amounts of iron are recycled daily with hemoglobin breakdown from destroyed old erythrocytes. Many recently identified proteins are involved in absorption, storage, and cellular export of nonheme iron and in erythroblast uptake and utilization of iron. Erythroblast heme levels regulate uptake of iron and globin synthesis such that iron deficiency causes red blood cell deficiencies by retarded production rates with smaller, less hemoglobinized erythrocytes.
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