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I Ortega-Blake

Publications and source records attributed to I Ortega-Blake.

9 recordsLinked to original sources
PubMed1998

On the role of sterol in the formation of the amphotericin B channel.

Amphotericin B is an antimycotic agent that has been studied for a long time, both because of its pharmacological action and the interest in understanding how this ionic channel works. It has been proposed that the channel is formed by a barrel of monomers, and that the presence of sterol is needed for the formation of such a barrel. As a matter of fact this need of a sterol has been used as a guiding idea in attempts to design derivatives more efficient in the discrimination of the cholesterol containing membranes, as compared to the ergosterol containing ones, henceforth diminishing the unwanted side effects in its pharmacological use. In this work we show that unitary channels that appear in a cholesterol containing membrane also appear when this membrane is free of cholesterol. We prove this to be the case for two membranes, a biological one, asolectin, and a synthetic one, DMPC. We then advance the idea that the role of sterols in the formation of the amphotericin B channel is related to the effects they have on the structure of the membrane itself, rather than to a direct involvement in the channel formation. We further look into the effect that different cholesterol concentrations in the membrane produce on the single channel properties.

Amphotericin B↗
PubMed1994

The role of hydration in the hydrolysis of pyrophosphate. A Monte Carlo simulation with polarizable-type interaction potentials.

The exchange of energy in biochemical reactions involves, in a majority of cases, the hydrolysis of phosphoanhydrides (P-O-P). This discovery has lead to a long discussion about the origin of the high energy of such bonds, and to a proposal that hydration plays a major role in the energetics of the hydrolysis. This idea was supported by recent ab initio quantum mechanical calculations (Saint-Martin et al. (1991) Biochim. Biophys. Acta 1080, 205-214) that predicted the hydrolysis of pyrophosphate is exothermic in the gas phase. This exothermicity can account for only a half of the total energy release that one measures in aqueous solutions. Here we address the problem of hydration of the reactants and products of the pyrophosphate hydrolysis by means of Monte Carlo simulations, employing polarizable potentials whose parameters are fitted to energy surfaces computed at the SCF/6-31G** level of the theory. The present results show that the hydration enthalpies of the reactants and products contribute significantly to the total energy output of the pyrophosphate hydrolysis. The study predicts that both, the orthophosphate and the pyrophosphate, have hydration spheres with the water molecules acting as proton acceptors in the P-OH ... O(water) hydrogen bonds. These water molecules weakly repel the water molecules in the further hydration spheres. The perturbation of the structure of the solvent caused by the presence of the solute molecules is short ranged: after ca. 5 A from the P atoms, the energy and the structure of water correspond to bulk water. Due mainly to nonadditive effects, the molecular structure of the hydrated pyrophosphate is quite different from two fused structures of the hydrated orthophosphates. The hydration sphere of pyrophosphate is very loose and has a limited effect on the water network, whereas for orthophosphate it has a well developed shell structure. Hence, upon hydration there will be both a gain in hydration enthalpy and a gain in entropy because of distortion of the water molecular network.

Action Potentials↗
PubMed1991

Ab initio calculations of the pyrophosphate hydrolysis reaction.

Ab initio quantum mechanical calculations were used to study the hydrolysis reaction H4P2O7 + H2O in equilibrium with 2H3PO4, as well as some molecular properties of the reactants and products. SCF calculations with several basis sets ranging from minimal to extended with polarization functions were used to look at the basis dependency of the reaction enthalpies and optimized geometries. Although the minimal basis sets yield erratic predictions of the enthalpy, when a more extended basis (3-21G*) was used for the geometry optimization, and the total energies of the reactants and products were computed with this and larger basis sets, we obtained more consistent predictions of the structural properties of the P-O-P bridge and of the heat of the hydrolysis reaction (delta E = -7.39 kcal/mol at the SCF/6-31G** level). A comparison is made with previous estimates performed with smaller basis sets and without taking into account the electron correlation effects, which are calculated in the present work. The inclusion of the zero point energy calculated using the harmonic approximation, and of the electronic correlation energy determined at the MBPT(2) level, raised the computed heat of the reaction to -3.83 kcal/mol, and when an estimate for the thermal energy was added, the value obtained was of -3.38 kcal/mol. In conclusion, we found that the hydrolysis of pyrophosphate should be exothermic in the gas phase. The implications of this result in relation to some recent theories about enzyme catalysis are discussed.

Diphosphates↗
PubMed1991

A microscopic electrostatic model for the amphotericin B channel.

A microscopic model of an amphotericin B channel is proposed. The structure of the pores is generated using the atomic coordinates of the molecule in the structure determined experimentally by X-ray diffraction. The net charges of the atoms are determined by Mulliken analysis. With these charges the electrostatic energy profiles are calculated for a monovalent ion passing through the channels formed by different number of antibiotic molecules having different radii. The water inside the channel was considered through a continuum medium using the dielectric constant of the bulk, and the membrane contribution was included using the virtual images of the pore in a dielectric slab of epsilon = 3. The model satisfactorily explains the permeability and selectivity characteristics as well as other observations yet unexplained. The electrostatic profiles obtained reinforce the hypothesis of the existence of channels formed by a variable number of units.

Amphotericin B↗
PubMed1991

Effect of Na(3)VO(4) on the P State of Nitella translucens.

The capacity of sodium orthovanadate to inhibit the plasmalemma H(+) ATPase of Nitella translucens internodal cells in vivo was tested. Here we show that 1 millimolar vanadate added externally depolarizes strongly and permanently the membrane potential, both in dark and light, to the Nernst potential for potassium consistent with pump inhibition by vanadate. From the results it is clear that the H(+) ATPase is always active, under light or dark conditions, in contradiction with the widespread idea of pump inactivation by darkness. The changes in conductance for light, dark, and vanadate-induced conditions are analyzed. The effect of dark on membrane passive permeabilities and on the possibility that some plasmalemma channels could be regulated by a phosphorylation-dephosphorylation process is discussed.

Journal Article↗
PubMed1985

A group theory analysis of the ambiguities in the genetic code: on the existence of a generalized genetic code.

It is known that in the transcription of genetic information there are ambiguities, i.e. the fact that a triplet codes for several aminoacids. This has generally been taken as due to errors in the transcription mechanisms. However, it has been postulated that instead of accidental miscoding, ambiguities are part of the expression of a generalized genetic code which depends on biological context. Group theory has been used to find the generalized genetic code. Here we present a new group theory approach which we think removes some weaknesses of previous works. The generalized genetic code presented here is different from that previously reported. We compare our results with experimental evidence and discuss the predictions presented.

Amino Acids↗