Mechanism of copper transport from plasma to hepatocytes

Conference · Sat Nov 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6840286

Ettinger, M J; Darwish, H M; Schmitt, R C

The effects of plasma components on the kinetics of copper transport by rat hepatocytes were examined in an attempt to determine how copper is mobilized from plasma for uptake by the liver. Specific protein-facilitated transport was indicated by saturation kinetics, competition by related substrates, and similar kinetic parameters for uptake and efflux. For copper uptake, K/sub m/ = 11 +/- 0.6 ..mu..M and V/sub max/ = 2.7 +/- 0.6 nmol Cu/(min x mg protein). Zinc is a competitive inhibitor of copper uptake, and copper competes for zinc uptake. Copper efflux from preloaded cells is biphasic. The kinetic parameters for the initial rapid phase are similar to the parameters for uptake. Copper transport by hepatocytes is strictly passive. A variety of metabolic inhibitors have no effect on uptake and initial rates are solely dependent on extracellular-intracellular concentration gradients. Albumin markedly inhibits copper intake by a substrate removal mechanism, and histidine facilitates albumin-inhibited copper uptake. The active species that delivers copper to hepatocytes under conditions of excess albumin and excess histidine is the His/sub 2/Cu complex. Experiments with (/sup 3/H)His/sub 2/ /sup 64/Cu showed that the transported species is free ionic copper. The kinetic parameters of copper transport by hepatocytes isolated from the brindled mouse model of Menkes' disease are normal. However, these cells show a decreased capacity to accumulate copper on prolonged incubation. An intracellular metabolic defect seems to be involved.

• Research Organization: State Univ. of New York, Buffalo
• OSTI ID: 6840286
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:12
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL MATERIALS
BLOOD
BLOOD PLASMA
BODY FLUIDS
COPPER
COPPER 64
COPPER ISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
ELEMENTS
HOURS LIVING RADIOISOTOPES
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LIVER CELLS
MAMMALS
MATERIALS
MEMBRANE TRANSPORT
METABOLISM
METALS
NUCLEI
ODD-ODD NUCLEI
RADIOISOTOPES
RATS
REACTION KINETICS
RODENTS
SOMATIC CELLS
TRACER TECHNIQUES
TRANSITION ELEMENTS
TRITIUM COMPOUNDS
UPTAKE
VERTEBRATES