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Biomedical subjects

M G Choc

Publications and source records attributed to M G Choc.

25 records · Page 2Linked to original sources
PubMed1987

Multiple-dose pharmacokinetics of clozapine in patients.

After a 2-day buildup, patients were dosed continuously with clozapine solution at three ascending dose levels (37.5, 75, and 150 mg bid for 7 days at each dose level). Following the morning administration on the twenty-third day of dosing a drug holiday was instituted which lasted for a minimum of 48 hr. Serial plasma samples were obtained during each of the periods and during the drug holiday for the calculation of the steady-state parameters AUCSS, CSSmax, and CSSmin at each dose level as well as for the assessment of the terminal elimination rate. Mean parameter values for AUCSS, CSSmax, and CSSmin showed a linearly increasing response with the dose, well described by a straight line passing through the origin. The terminal elimination appeared to follow linear kinetics and had a mean half-life of 15.8 hr (range, 5.8-33 hr).

Adolescent↗
PubMed1984

Respiratory proteins from the extremely thermophilic aerobic bacterium, Thermus thermophilus. Purification procedures for cytochromes c552, c555,549, and c1aa3 and chemical evidence for a single subunit cytochrome aa3.

We have developed a chemically defined, minimal growth medium for Thermus thermophilus which is suitable for nutritional studies, isotopic enrichment, and genetic manipulation of the organism. Reliable procedures are described for the large scale purification of cytochrome c552 from the periplasm and for cytochrome c555,549 and cytochrome c1 aa3 from the plasma membrane. In contrast to a previous report (Fee, J. A., Choc, M. G., Findling, K. L., Lorence, R., and Yoshida, T. (1980) Proc. Natl. Acad. Sci. U. S. A. 77, 147-151) which suggested a molecular weight near 200,000, the cytochrome c1aa3 complex was shown by protein and amino acid analyses to have Mr approximately 93,000. Sodium dodecyl sulfate-urea-polyacrylamide gel electrophoresis and reversed phase high performance liquid chromatography, combined with amino acid analyses, revealed the presence of only two proteins in a 1:1 ratio: C-protein has Mr approximately 33,000, binds heme C, and is thought to correspond to cytochrome c1. A-protein has Mr approximately 55,000 and is thought to bind the four redox components (2 heme A and 2 Cu) of cytochrome aa3.

Amino Acids↗
PubMed1981

Evidence from infrared and 13C NMR spectra for discrete rapidly interconverting conformers at the carbon monoxide binding sites of hemoglobins A and Zurich.

Fully liganded hemoglobin carbonyls in solution exhibit infrared and 13C NMR spectra that indicate the normal presence of discrete, rapidly interconverting conformers at the carbon monoxide binding sites. The CO ligands bound to Hb A give infrared bands with vCO = 1968 and 1951 cm-1. With Hb Zurich [beta 63 His leads to Arg], vCO values of 1968, 1958, and 1951 cm-1 are observed. Changing either the temperature (3-32 degrees C) or the pH (4 to 11.9) produces reversible redistributions of individual infrared band intensities without a significant change in the total integrated intensity for all bands; only small shifts in frequency occur. In 13C NMR spectra for 13C16O ligands only one resonance is observed for each type of subunit: alpha A and alpha Zh at approximately 206.4 ppm, beta A at approximately 206.0 ppm, beta Zh at approximately 205.5 ppm, each from tetramethylsilane. Since the multiple conformers observed in infrared spectra are not evident in the 13C NMR spectra, the interconversions among the conformers are considered to be too rapid for the individual conformers to be detected by NMR spectroscopy. Estimated differences in enthalpy and in entropy between the separate conformers range from 1.5 to 5.2 kcal/mol and 6.6 to 11.5 entropy units, respectively. The structural differences between carbonyl conformers are sufficiently great that iron (II)--CO bonding and the reactivity of the individual conformers are expected to vary significantly. These findings demonstrate a dynamic aspect of structure due to the flexibility of the protein at the ligand binding site that is important in any consideration of structure-function or structure-property relationships.

Binding Sites↗
PubMed1981

Dynamic protein structures: infrared evidence for four discrete rapidly interconverting conformers at the carbon monoxide binding site of bovine heart myoglobin.

Infrared spectra for the carbon monoxide complex with myoglobin isolated as the oxygenyl species from bovine heart muscle were carefully examined in the C--O stretch region as either the pH or the temperature was varied. Deconvolutions of these spectra into bands of Gaussian shape suggest the presence of four bands near 1938(I), 1944(II), 1954(III), and 1965(IV) cm-1 with halfband widths of about 18, 9, 9, and 10 cm-1, respectively. The relative intensities of the four bands varied with changes in pH or temperature. 13C NMR spectra and other evidence indicate that the four C--O stretch bands arise from four discrete rapidly interconverting conformers: CI, CII, CIII, and CIV. Under conditions of physiological pH and temperature, the relative stabilities are CI approximately CII much greater than CIII approximately CIV. The delta H and delta S values for conformer interconversions are estimated to range from -8 to 34 kJ/mol and -27 to 87 J.mol-1 K-1, respectively; therefore the structures of the conformers may be expected to vary significantly. These findings provide evidence for a highly flexible, dynamic structure at the ligand-binding site of bovine myoglobin, even when ligands are bound.

Animals↗
PubMed1980

Properties of a copper-containing cytochrome c1aa3 complex: a terminal oxidase of the extreme thermophile Thermus thermophilus HB8.

From the plasma membrane of Thermus thermophilus HB8 we have partially purified a detergent-solubilized complex of cytochromes a and c1 that actively catalyzes the transfer of electrons from ascorbate via a redox dye to oxygen. The complex is composed of two types of polypeptides, with molecular weights of approximately 55,000 and 33,000. Quantitative analysis revealed the presence of heme a, heme c, and copper in a ratio of 2:1:2, with the heme a being present at 10 +/- 1.3 nmol/mg of protein. The heme c was shown to be associated with the molecular weight 33,000 peptide and is suggested to be of the c1 type. The optical and electron paramagnetic resonance properties of this complex were found to be similar to those of eukaryotic cytochrome oxidase, suggesting the following arrangement of chromophores: a magnetically isolated cytochrome c1 and an oxygen-reducing functional unit consisting of two heme a groups and two copper ions associated with one or more larger peptides.

Copper↗