Modulation of bone marrow heme and protein synthesis by trace elements. [Rats]

Journal Article · Tue Jun 01 00:00:00 EDT 1982 · Environ. Res.; (United States)

OSTI ID:6928360

Dresner, D L; Ibrahim, N G; Mascarenhas, B R; Levere, R D

The effect of heavy metals and trace elements, such as Cu, Au, Cd, Zn, and Pb, on heme synthetic and degradatory enzymes in rat bone marrow suspensions was examined. Cu, Cd, and Au, at a low concentration of 5 x 10/sup -6/ M, inhibited delta-aminolevulinic acid (deltaALA) dehydratase by 61, 47, and 47% respectively. A similar concentration of Zn did not inhibit the enzyme activity and, in fact, was able to protect against Au and Pb inhibition in the normal marrow. Cd was unable to recover any of the enzyme activity and, in fact, caused further inhibition. Cu and Au, at a concentration of 10/sup -5/ M, inhibited leucine incorporation into marrow globin and nonglobin protein by 26 and 34%, respectively. Substantially higher concentrations of Zn, as well as Fe, were required to inhibit leucine incorporation into protein. These studies led to the postulation that the inhibition of deltaALA dehydratase by heavy metals was directly related to the inhibition of heme and protein synthesis in the bone marrow cell suspensions. These results suggest that trace elements by themselves or in a combination reduce the capacity of the erythroid cell to synthesize heme, the prosthetic group of many hemoproteins. In addition, we have shown that in an iron-overloaded rat the bone marrow contains approximately 45% more heme oxygenase activity than that of the control. Administration of Au alone did not increase heme degradation, but the combination of Fe and Au resulted in a marked induction of heme oxygenase. Finally, for the first time we were able to demonstrate that excess iron and/or decreased Zn concentration may predispose deltaALA dehydratase to inhibition by an interaction with other metals, such as Pb, by an undefined mechanism(s).

• Research Organization: New York Medical Coll., Valhalla
• OSTI ID: 6928360
• Journal Information: Environ. Res.; (United States), Vol. 28:1
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
59 BASIC BIOLOGICAL SCIENCES
CADMIUM
BIOLOGICAL EFFECTS
COPPER
ENZYME ACTIVITY
INHIBITION
GOLD
HEME
LEAD
ZINC
BIOSYNTHESIS
BONE MARROW
CONCENTRATION RATIO
IRON
RATS
SYNERGISM
TRACE AMOUNTS
ANIMAL TISSUES
ANIMALS
BODY
CARBOXYLIC ACIDS
ELEMENTS
HEMATOPOIETIC SYSTEM
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
MAMMALS
METALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PIGMENTS
PORPHYRINS
RODENTS
SYNTHESIS
TISSUES
TRANSITION ELEMENTS
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
550200 - Biochemistry