Biosynthesis of heme in immature erythroid cells

Journal Article · Sun May 15 04:00:00 EDT 1988 · J. Biol. Chem.; (United States)

OSTI ID:6771982

Gardner, L C; Cox, T M

Heme formation in reticulocytes from rabbits and rodents is subject to end produce negative feedback regulation: intracellular free heme has been shown to control acquisition of transferrin iron for heme synthesis. To identify the site of control of heme biosynthesis in the human erythron, immature erythroid cells were obtained from peripheral blood and aspirated bone marrow. After incubation with human /sup 59/Fe transferrin, 2-(/sup 14/C)glycine, or 4-(/sup 14/C)delta-aminolevulinate, isotopic incorporation into extracted heme was determined. Addition of cycloheximide to increase endogenous free heme, reduced incorporation of labeled glycine and iron but not delta-aminolevulinate into cell heme. Incorporation of glycine and iron was also sensitive to inhibition by exogenous hematin. Hematin treatment rapidly diminished incorporation of intracellular /sup 59/Fe into heme by human erythroid cells but assimilation of 4-(/sup 14/C)delta-aminolevulinate into heme was insensitive to inhibition by hematin. In human erythroid cells (but not rabbit reticulocytes) pre-incubation with unlabeled delta-aminolevulinate or protoporphyrin IX greatly stimulated utilization of cell /sup 59/Fe for heme synthesis and also attenuated end product inhibition. In human erythroid cells heme biosynthesis is thus primarily regulated by feedback inhibition at one or more steps which lead to delta-aminolevulinate formation. Hence in man the regulatory process affects generation of the first committed precursor of porphyrin biosynthesis by delta-aminolevulinate synthetase, whereas in the rabbit separate regulatory mechanisms exist which control the incorporation of iron into protoporphyrin IX.

• Research Organization: Hammersmith Hospital, London (England)
• OSTI ID: 6771982
• Journal Information: J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 263:14; ISSN JBCHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
AMINOLEVULINIC ACID
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BIOSYNTHESIS
BLOOD
BLOOD CELLS
BLOOD COAGULATION FACTORS
BODY FLUIDS
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CELL DIFFERENTIATION
COAGULANTS
DAYS LIVING RADIOISOTOPES
DRUGS
ERYTHROCYTES
EVEN-ODD NUCLEI
GLYCINE
HEMATOLOGIC AGENTS
HEME
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
INTERMEDIATE MASS NUCLEI
IRON 59
IRON ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
MAN
MATERIALS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PIGMENTS
PORPHYRINS
PRIMATES
RABBITS
RADIOISOTOPES
RETICULOCYTES
SYNTHESIS
VERTEBRATES