Biosynthesis of heme in immature erythroid cells. The regulatory step for heme formation in the human erythron

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

OSTI ID:7070282

Gardner, L C; Cox, T M

Heme formation in reticulocytes from rabbits and rodents is subject to end product 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 59Fe transferrin, 2-(14C)glycine, or 4-(14C)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 (Ki, 30 and 45 microM, respectively) i.e. at concentrations in the range which affect cell-free protein synthesis in reticulocyte lysates. Hematin treatment rapidly diminished incorporation of intracellular 59Fe into heme by human erythroid cells but assimilation of 4-(14C)delta-aminolevulinate into heme was insensitive to inhibition by hematin (Ki greater than 100 microM). In human reticulocytes (unlike those from rabbits), addition of ferric salicylaldehyde isonicotinoylhydrazone, to increase the pre-heme iron pool independently of the transferrin cycle, failed to promote heme synthesis or modify feedback inhibition induced by hematin. In human erythroid cells (but not rabbit reticulocytes) pre-incubation with unlabeled delta-aminolevulinate or protoporphyrin IX greatly stimulated utilization of cell 59Fe 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.

• Research Organization: Hammersmith Hospital, London (England)
• OSTI ID: 7070282
• 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
ANIMAL TISSUES
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BIOSYNTHESIS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
BONE MARROW
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CYCLOHEXIMIDE
DAYS LIVING RADIOISOTOPES
DRUGS
ERYTHROCYTES
EVEN-ODD NUCLEI
FEEDBACK
FUNCTIONS
FUNGICIDES
GLOBIN
GLOBULINS
GLOBULINS-BETA
GLYCINE
HEMATOPOIETIC SYSTEM
HEME
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
INHIBITION
INTERMEDIATE MASS NUCLEI
IRON 59
IRON ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
LIPOTROPIC FACTORS
MAMMALS
MAN
MATERIALS
METALLOPROTEINS
METHIONINE
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PESTICIDES
PIGMENTS
PORPHYRINS
PRIMATES
PROTEINS
RABBITS
RADIOISOTOPES
RETICULOCYTES
SYNTHESIS
TISSUES
TRACER TECHNIQUES
TRANSFERRIN
VERTEBRATES