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Biomedical subjects

R Brodersen

Publications and source records attributed to R Brodersen.

At least 91 records · Page 5Linked to original sources
PubMed1977

Binding of bilirubin and long-chain fatty acids to human serum albumin with general remarks on displacement of firmly bound ligands.

Binding of bilirubin to human serum albumin was studied by estimation of the free bilirubin concentration from the rate of oxidation with hydrogen peroxide and peroxidase, and by spectrophotometry: nI = 1, kI = 7 x 10(7) l/mol; nII = 1, kII = 5 x 10)5) l/mol, at pH 7.4, 37 degrees C, ionic strength 0.1. Palmitate or oleate in excess of 4 mol per mol albumin, influences the high-affinity binding of bilirubin as described by an empirical equation. Theoretical consideration of competitive displacement of a biologically active substance, firmly bound in an inactive state to a macromolecular carrier, demonstrates that significant displacement may occur on addition of another ligand with a lower binding constant. Displacement of bilirubin from its high-infinity site by fatty acids and drugs is thermodynamically feasible and probably clinically important.

Bilirubin↗
PubMed1977

Photooxidation of human serum albumin and its complex with bilirubin.

Irradiation with visible light of human serum albumin in aqueous solution at pH 8, in the presence of catalytic amounts of rose bengal or methylene blue, resulted in random oxidation of the histidine residues in the protein under consumption of one mole O2, and release of somewhat less than one proton, per histidine residue degraded. An increase of light absorption at 250 nm was proportional to the amount of oxygen consumed. Bilirubin bound to the oxidized protein showed an increased light absorption at its maximum, 460 nm, and a decreased binding affinity, indicating a conformational change of the protein on oxidation of histidine residues. This change also resulted in a slight perturbation of tyrosine light absorption, corresponding to a shift of the chromophore to more polar surroundings. Further, a sensitized oligomerization of albumin was observed, independent of oxidation of the histidine residues, and not consuming oxygen. Irradiation of a complex of human serum albumin with one molecule of bound bilirubin, in the absence of a sensitizing dye, resulted in a fast, non-oxygen consuming process whereby the light absorption maximum of the pigment was shifted 4 nm towards longer wavelength and part of the bilirubin was converted to a more polar pigment, bound less firmly to the protein. This was followed by a relatively slow oxidation of the pigment under uptake of one mole O2. Parallel photooxidation of the protein carrier could not be detected. It is considered possible that the fast, anaerobic process is operative in phototherapy of hyperbilirubinemia in the newborn. Serum albumin is probably not oxidized during this treatment.

Bilirubin↗
PubMed1977

Bilirubin displacing effect of stabilizers added to injectable preparations of human serum albumin.

Stabilizers added to preparations of human serum albumin before heat treatment were tested for bilirubin displacing effect, using the peroxidase method. It was found that N-acetyltryptophan and sodium caprylate displace bilirubin from its complex with human serum albumin in vitro. The quantitative findings were used for a rough estimate of the effect of these substances on the free bilirubin concentration in blood plasma, expected when stabilized albumin preparations are given intravenously for prevention of kernicterus. The calculated effect is a delay of the decrease of free bilirubin concentration, or even a temporary increase. Sodium mandelate displaces less strongly.

Bilirubin↗
PubMed1977

Prevention of kernicterus, based on recent progress in bilirubin chemistry.

A review is presented of recent progress in bilirubin chemistry, its binding to albumin, displacement by drugs, and the mechanism of phototherapy. Quantitative formulations of the effect of albumin dosage, of varying pH, and of fatty acids result in a diagram which may be tried as an aid to indications for therapy.

Albumins↗
PubMed1974

Competitive binding of bilirubin and drugs to human serum albumin studied by enzymatic oxidation.

The mechanism of drug-induced displacement of bilirubin from the blood into tissues was studied. A model of simple, competitive binding of bilirubin and drug to one site on serum albumin was established. Variations of the free bilirubin concentration after addition of drugs were studied in vitro by measuring velocities of oxidation with hydrogen peroxide and horseradish peroxidase. In all cases, the results were in agreement with the model. The competitive effects of 20 drugs were measured and expressed quantitatively as binding constants to the bilirubin site on human serum albumin. Several drugs caused changes of the bilirubin-albumin light absorption spectrum, indicating simultaneous binding of both ligands, without an effect on the free bilirubin concentration. Noncompetitive site-to-site effects on bilirubin binding could not be demonstrated. An equation is proposed for calculation of the maximal displacing effect of a drug from knowledge of its plasma concentration, the above-determined binding constant, and the degree of protein binding of the drug. Comparison of these results with previous observations of bilirubin displacement in newborn humans and in experimental animals indicates a general agreement with a simple competitive mechanism of binding of bilirubin and drug to one site on the albumin molecule. Binding of drugs to other, noncompetitive sites is common.

Anti-Bacterial Agents↗