Specific site inhibitors of NAD-specific isocitrate dehydrogenase from bovine heart.
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Animals↗
Biomedical subjects
J L Gabriel
Publications and source records attributed to J L Gabriel.
Comparative studies of kinetic and optical properties of rabbit muscle, sturgeon muscle, and yeast pyruvate kinase.
The kinetic and optical properties of pyruvate kinase isolated from rabbit muscle, sturgeon muscle, and yeast were compared using various activating divalent metal ions as probes for functional features and using ultraviolet circular dichroism (cd) measurements for conformational features, respectively. All three preparations of pyruvate kinase were similar in many aspects, such as activating efficiencies of the four activating metal ions, Mg(II), Co(II), Mn(II), and Ni(II) and pH-rate profiles, suggesting the presence of a similar metal binding locus of these enzymes as well as a common underlying mechanism of action. L-Phe inhibited the rabbit muscle enzyme and turned the hyperbolic kinetics into a sigmoidal kinetic with respect to phosphoenolpyruvate at alkaline pH, while fructose-1,6-biphosphate activated the sturgeon muscle and yeast enzymes and turned the sigmoidal kinetics into hyperbolic kinetics with respect to phosphoenolpyruvate. The ultraviolet cd spectral changes qualitatively correlated well with kinetic observations of all three native enzymes in the presence and absence of allosteric effectors. Our results suggested that there are at least two conformational states of pyruvate kinase which are inducible by the binding of substrate and (or) allosteric effectors. The conformational changes from one form to another in these enzymes are very similar, especially between the rabbit and sturgeon muscle enzymes.
Animals↗
Circular dichroism of cobaltous complexes of creatine kinase.
Circular dichroic spectra in the visible wavelength region were used to investigate the local environment of Co(II), an activating metal, at the active site of rabbit muscle creatine kinase. There was a small spectral change when CoADP- was bound to creatine kinase, no change when creatine was added, and another small change when NO3- was added to form the transition state analogue. Using matrix rank analysis to quantitate these small spectral changes, a titratable group with a pK = 7.4 was found which modified the enzyme-bound metal-nucleotide interaction. These data suggest that, throughout the enzyme's catalysis, the metal-nucleotide interaction remains very similar in structure to the complex not bound to the enzyme.
Adenosine Diphosphate↗
Quantitative structure-activity relationships of perfluorinated hetero-hydrocarbons as potential respiratory media. Application to oxygen solubility, partition coefficient, viscosity, vapor pressure, and density.
It has been extensively reported that liquid-assisted ventilation, using inert perfluorocarbon liquids (PFCs), can reduce interfacial surface tension and allow for improved ventilation at decreased alveolar pressures. PFCs are bioinert, minimally absorbed, and have no deleterious histologic, cellular, or biochemical effects when used as respiratory media. Although several types of PFCs have been characterized, a select few are considered to be compatible with life. Compatibility is often related to the physicochemical profile inherent to the PFC liquids. It is essential that certain physical properties such as respiratory gas solubility, vapor pressure, density, viscosity, and tissue permeability be within a narrow, acceptable range for a PFC to be considered as a possible candidate for respiratory media. The current study sought to characterize the physicochemical profile of commercially available PFCs. This was accomplished by creating a method for accurate, rapid prediction of a host of unknown physical characteristics of PFCs. The physicochemical properties of 16 perfluorinated hetero-hydrocarbons were catalogued from the literature. The input data were categorized into three major groups: empiric properties, geometric indices, and quantum mechanical descriptors, to generate a database. Algorithms were then developed, one for each dependent variable (FUNCTION), including oxygen solubility, partition coefficient (logP), vapor pressure, viscosity, and density, that related the values of these physical properties of potential breathable PFC liquids to the parameters listed in the database. The general form of the algorithm can be written as follows: FUNCTION = sigma (CiPi/magnitude of Pi) + constant; where the FUNCTIONS are oxygen solubility, logP, vapor pressure, viscosity, and density. Ci is a coefficient that weights the relative contribution of each parameter. Each independent parameter, Pi, was normalized by the average value of the parameter used in the analysis, magnitude of Pi. Residual analysis demonstrated validity with all five equations. This method is expected to assist in the prediction of physical properties of PFC liquids with acceptable accuracy, such that PFC production and selection from currently available liquids can be optimized for each liquid ventilation application.
Absorption↗