Control of heme synthesis during Friend cell differentiation: role of iron and transferrin

Journal Article · Sat Nov 01 04:00:00 EST 1986 · J. Cell. Physiol.; (United States)

DOI:https://doi.org/10.1002/jcp.1041290209· OSTI ID:6792582

Laskey, J D; Ponka, P; Schulman, H M

In many types of cells the synthesis of sigma-aminolevulinic acid (ALA) limits the rate of heme formation. However, results from this laboratory with reticulocytes suggest that the rate of iron uptake from /sup 125/I-transferrin (Tf), rather than ALA synthase activity, limits the rate of heme synthesis in erythroid cells. To determine whether changes occur in iron metabolism and the control of heme synthesis during erythroid cell development Friend erythroleukemia cells induced to erythroid differentiation by dimethylsulfoxide (DMSO) were studied. While added ALA stimulated heme synthesis in uninduced Friend cells (suggesting ALA synthase is limiting) it did not do so in induced cells. Therefore the possibility was investigated that, in induced cells, iron uptake from Tf limits and controls heme synthesis. Several aspects of iron metabolism were investigated using the synthetic iron chelator salicylaldehyde isonicotinoyl hydrazone (SIH). Both induced and uninduced Friend cells take up and utilize Fe for heme synthesis directly from Fe-SIH without the involvement of transferrin and transferrin receptors and to a much greater extent than from saturating levels or /sup 59/Fe-Tf (20 ..mu..M). Furthermore, in induced Friend cells 100 ..mu..M Fe-SIH stimulated 2-/sup 14/C-glycine incorporation into heme up to 3.6-fold as compared to the incorporation observed with saturating concentrations of Fe-Tf. These results indicate that some step(s) in the pathway of iron from extracellular Tf to protoporphyrin, rather than the activity of ALA synthase, limits and controls the overall rate of heme and possibly hemoglobin synthesis in differentiating Friend erythroleukemia cells.

• Research Organization: Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec
• OSTI ID: 6792582
• Journal Information: J. Cell. Physiol.; (United States), Journal Name: J. Cell. Physiol.; (United States) Vol. 129:2; ISSN JCLLA
• Country of Publication: United States
• Language: English

Related Subjects

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59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
AMINOLEVULINIC ACID
ANIMAL CELLS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMISTRY
BIOSYNTHESIS
CARBON 14 COMPOUNDS
CARBOXYLIC ACID SALTS
CARBOXYLIC ACIDS
CELL DIFFERENTIATION
CHEMISTRY
CHLORIDES
CHLORINE COMPOUNDS
CITRATES
DAYS LIVING RADIOISOTOPES
DISEASES
DMSO
ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
GLOBULINS
GLOBULINS-BETA
GLYCINE
HALIDES
HALOGEN COMPOUNDS
HEME
HEMIC DISEASES
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
IRON 59
IRON CHLORIDES
IRON COMPOUNDS
IRON ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
LEUKEMIA
LIGANDS
METALLOPROTEINS
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PIGMENTS
PORPHYRINS
PROTEINS
RADIOISOTOPES
SULFOXIDES
SYNTHESIS
TRANSFERRIN
TRANSITION ELEMENT COMPOUNDS
TUMOR CELLS
UPTAKE