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Biomedical subjects

C G Morley

Publications and source records attributed to C G Morley.

At least 19 recordsLinked to original sources
PubMed1985

Cellular iron uptake from transferrin: is endocytosis the only mechanism?

Receptor mediated endocytosis has been proposed as the method of cellular iron uptake from transferrin (TF). However, the experimental evidence for endocytosis in every situation is found wanting. This is particularly true for the hepatocyte where an alternative mechanism of iron release at the cell surface can account for all iron uptake. It may be, that under appropriate physiological conditions (e.g. degree of iron saturation of TF) cells may take up iron by either an endocytotic or nonendocytotic mechanism.

Animals↗
PubMed1983

The behavior of transferrin receptors in rat hepatocyte plasma membranes.

The liver serves as a storage organ for iron, 2-5 mg of Fe being exchanged between plasma and liver daily in the human being. Such iron transfer from serotransferrin (TF) to hepatocytes involves a TF receptor. We are reporting some of the properties of this receptor using isolated rat hepatocyte membranes as the receptor source. Iron-saturated 125I-rat TF was used for these studies. Specific versus nonspecific TF binding was evaluated by labelling the membranes with 125I-TF and then displacing specific binding with excess unlabelled TF. A mean residency time of 18-20 min was calculated for the TF on each receptor molecule. There were 31,000 +/- 17,000 receptors/cell with a dissociation constant of 0.3 X 10(-7) mol/l. The binding obeyed simple Michaelis-Menten kinetics. Specifically bound iron-saturated 125I-TF could best be eluted with cold Fe-saturated TF; cold apo- and 50% saturated TFs were less effective. The binding of apo- and 50% saturated TF was much less pronounced than that of Fe-saturated TF. The membrane receptor was moderately heat stable, extractable with detergent, and was trypsin sensitive. Studies with 125I/59Fe-TF and whole cells suggested that Fe-TF is not in a major way internalized during iron uptake. It is concluded that there are TF receptors present on the rat hepatocyte plasma membrane that may have a role in uptake by the cells without internalization of the TF molecule.

Animals↗
PubMed1983

Iron metabolism pathways in the rat hepatocyte.

A small to moderate inhibitory effect of iron uptake by isolated rat hepatocytes in short-term studies was seen with oxidative phosphorylation and electron transport inhibitors, and no inhibition by agents affecting pinocytosis. Intracellular transferrin was able to donate iron to the small-molecular weight iron pool, and the latter was able to transfer, by a process not requiring energy or movement of serum transferrin, iron to ferritin. Serum transferrin was not able to lose iron to any cytosol components. Reducing agents were not able to abstract iron from rat serum transferrin to any great extent. It is concluded that iron is taken up by the rat hepatocyte from serum transferrin by a process not requiring energy or movement of serum transferrin into the cell interior; and that intracellular transferrin is involved in acquiring iron from serum transferrin at the cell surface, with iron then being transferred to the small-molecular weight iron pool and hence to ferritin. It is also proposed that intracellular transferrins may have the general function of interacting with serum transferrin at cell surfaces.

Animals↗
PubMed1977

Stimulation of hepatocellular proliferation by a serum factor from thioacetamide-treated rats.

Rats treated with thioacetamide undergo hepatocellular proliferation reminscent of liver regeneration following partial hepatectomy. 36 h after administration of 50 mg thioacetamide/kg body weight to rats, [3H]thymidine incorporation into hepatic DNA reaches a peak of 78-10(3) dpm/mg DNA compared to a control of 3.2-10(3) dpm/mg DNA. Serum obtained from 6 to 48 h after administration of thioacetamide to rats stimulated hepatic but not kidney DNA synthesis in mice and rats. Autoradiography revealed an increase in the incorporation of labelled thymidine into the nuclei of mouse hepatocytes. The mitotic index of the liver was also increased. The serum factor stimulating these changes in the liver was non-dialyzable and heat stable. These results indicate that thioacetamide induced liver injury results in a humoral factor which stimulates DNA synthesis in rat and mouse identified in the serum from partially hepatectomized rats.

Acetamides↗
PubMed1977

The role of the liver in glucagon metabolism.

Total plasma immunoreactive pancreatic glucagon (IRG) was measured in samples taken simultaneously from the proximal portal vein and superior vena cava of 26 healthy rats. The portal-peripheral ratio of IRG was 2.80+/-0.25, the portal-peripheral difference (Delta) 124+/-15 pg/ml, and percentage extraction 58+/-3. Gel filtration of paired portal and peripheral vein samples showed that reduction in the 3,500-dalton IRG component (glucagon) in peripheral samples accounted for almost all the differences, there being minimal and inconsistent changes in the high molecular weight (>40,000) fraction. The portal-peripheral ratio of the 3,500-dalton glucagon was 5.24+/-1.10, the portal-peripheral difference 130+/-33 pg/ml, and the percentage extraction 81+/-5. To study the transhepatic differences in the 9,000-dalton "proglucagon-like" material, the experiment was repeated in nine rats 24 h after bilateral nephrectomy, a procedure which increases plasma levels of this fraction. The portal-peripheral ratio for plasma IRG in these rats was 1.48+/-0.12, the portal-peripheral difference 140+/-29 pg/ml, and percentage extraction 28+/-5. Gel filtration revealed no consistent differences between portal and peripheral concentrations of the 9,000- and >40,000-dalton components, which comprised 40 and 13%, respectively, of the mean IRG level of 492+/-35 pg/ml. In contrast, there were marked differences between portal and peripheral levels of the 3,500-dalton component the ratio being 3.42+/-0.63, the portal-peripheral difference 182+/-32 pg/ml, and percentage extraction 64+/-5. Similar studies in a healthy dog, in which species there are significant circulating levels of the 9,000-dalton IRG component, confirmed the selective hepatic extraction of the 3,500-dalton fraction. We conclude that the various IRG fractions are metabolized differently by the liver, and that portal-peripheral ratios based on direct assay of plasma IRG will vary depending on the percentage glucagon immunoreactivity in each fraction; the greater the combined contribution of fractions other than the 3,500-dalton component to total plasma IRG, the lower will be the ratio. Because of the heterogeneity of circulating IRG and significant differences in the metabolism of its various components, gel filtration of plasma samples is necessary for precise quantitation of the hepatic uptake of each particular fraction.

Animals↗
PubMed1976

The regulation of mouse liver ornithine decarboxylase by metabolites.

The enzyme ornithine decarboxylase (L-Ornithine carboxy-lyase, EC 4.1.1.17), has been partially purified from the livers of mice subjected to partial hepatectomy (6-8 h previously). Mouse liver ornithine decarboxylase requires pyridoxal phosphate, and dithiothreitol for maximal activity. The enzyme has a pH optimum of 7.3, it is inhibited in the presence of 0.3 M phosphate, glycine, Tricine and Tris. It shows no dependence on metal ions and is inhibited by high salt concentrations, particularly ammonium salts. The kinetics of the enzyme have been studied with putrescine (and analogs), spermidine and spermine, in the presence of both high and low levels of pyridoxal phosphate. High concentrations of pyridoxal phosphate inhibit the enzyme. The enzyme is also inhibited by low concentrations of putrescine (1 mM). As the concentration of putrescine increased to 10 mM, non-competitive inhibition was observed, this could be reversed by addition of higher levels of pyridoxal phosphate. Spermidine and spermine inhibit (noncompetitively) only at high concentrations (10 mM). Ornithine inhibits at high concentrations (2 mM). Spectral studies have shown that the observed kinetics of competitive inhibition at low concentrations of polyamine changing to noncompetitive inhibition at high polyamine concentrations are due to competition between enzyme and substrate (or inhibitor) for free (non-enzyme bound) pyridoxal phosphate. Noncompetitive inhibition arises through the formation of transient Schiff base complexes between amines and free pyridoxal phosphate. It also appears that the binding of substrate to the active site takes place through Schiff base formation with enzyme bound pyridoxal phosphate.

Animals↗