Transport properties of single-file pores with two conformational states.

Complex facilitative membrane transporters of specific ligands may operate via inner channels subject to conformational transitions. To describe some properties of these systems, we introduce here a kinetic model of coupled transport of two species, L and w, through a two-conformational pore. The basic assumptions of the model are: a) single-file of, at most, n molecules inside the channel; b) each pore state is open to one of the compartments only; c) there is at most only one vacancy per pore; d) inside the channel, a molecule of L occupies the same positions as a molecule of w; and e) there is at most only one molecule of L per pore. We develop a general representation of the kinetic diagram of the model that is formally similar to the one used to describe one-vacancy transport through a one-conformational single-file pore. In many cases of biological importance, L could be a hydrophilic (ionic or nonionic) ligand and w could be water. The model also finds application to describe solute (w) transport under saturation conditions. In this latter case, L would be another solute, or a tracer of w. We derive steady-state expressions for the fluxes of L and w, and for the permeability coefficients. The main results obtained from the analysis of the model are the following. 1) Under the condition of equilibrium of w, the expression derived for the flux of L is formally indistinguishable from the one obtainable from a standard four-state model of ligand transport mediated by a two-conformational transporter. 2) When L is a tracer of w, we can derive an expression for the ratio between the main isotope and tracer permeability coefficients (Pw/Pd). We find that the near-equilibrium permeability ratio satisfies (n - 1) < or = (Pw/Pd)eq < or = n, a result previously derived for the one-conformational, single-file pore for the case that n > or = 2. 3) The kinetic model studied here represents a generalization of the carrier concept. In fact, for the case that n = 1 (corresponding to the classical single-occupancy carrier), the near-equilibrium permeability ratio satisfies 0 < or = (Pw/Pd)eq < or = 1, which is characteristic of a carrier performing exchange-diffusion.     

Electrophysiological characteristics of cardiac pacemaker cells of the frog Caudiverbera caudiverbera

1. The cardiac pacemaker cells of the frog Caudiverbera caudiverbera are centrally located in the sinus venosus. These cells are rounded, smaller than contractile fibres and have large nuclei. 2. Intracellular recording confirmed the existence of primary and transitional pacemaker cells. 3. Action potentials from primary cells were resistant to blockade by tetrodotoxin (TTX), but were abolished by verapamil suggesting that their bioelectric activity is dependent on a slow inward current. 4. Transitional cells appeared to have two different inward currents contributing to the upstroke: a fast TTX-sensitive and a slow verapamil-sensitive current.     

Effect of feeding pattern on the sensitivity of hepatic carnitine palmitoyl-transferase to inhibition by malonyl-CoA in the rat

1. The feeding pattern influences the inhibitory effects of malonyl-CoA on carnitine palmitoyltransferase-I. 2. The sensitivity of liver carnitine palmitoyltransferase-I to malonyl-CoA is increased in rats meal-fed when compared to rats fed ad libitum. 3. Moreover, liver carnitine palmitoyltransferase-I of meal-fed rats remains more sensitive to inhibition by malonyl-CoA during a 24 hour fast than liver carnitine palmitoyltransferase-I of rats previously fed ad libitum.     

Correlation of pause sites in MDV-1 RNA replication with kinetic refolding of the growing chain. A Monte Carlo simulation of the Markov process

We consider a template-instructed MDV-1 RNA replication catalyzed by Q beta replicase. The relaxation of the effective binding of the growing chain to the enzyme is simulated, considering a Markov process where refolding events in the chain are concomitant with chain elongation events. When realistic transition probabilities are considered, it becomes evident that the pause sites in replication are due to relaxation of the binding by folding of the growing chain.     

Nitrogen-source-induced activation of neutral trehalase in Schizosaccharomyces pombe and Pachysolen tannophilus: role of cAMP as second messenger

Abstract Resting cells of the fission yeast Schizosaccharomyces pombe , suspended in buffer with glucose, responded to the addition of asparagine by increasing trehalase activity. This response was preceded by a peak in cAMP concentration. The addition of the nitrogen source to resting cells, devoid of the catalytic subunit of cAMP-dependent protein kinase, produced the transient increase in cAMP but did not promote any change in trehalase activity. In the budding yeast Pachysolen iannophilus , the activation of trehalase by nitrogen source was also accompanied by a sharp peak in cAMP. These results suggest that in the two yeasts cAMP acts as a second messenger in the transduction of the nitrogen-source-induced signal causing the activation of trehalase.     

Plasma somatostatin-like immunoreactivity during growth-hormone-releasing hormone therapy in non-growth-hormone-deficient children

To date, the effects of long-term growth hormone (GH)-releasing hormone [GHRH(1-29)-NH2] treatment on the plasma concentrations of somatostatin-like immunoreactivity (SLI) remain undefined. In the present study, the effect of GHRH(1-29)-NH2 therapy on plasma SLI levels has been studied in 11 non-GH-deficient children. The pattern of administration was 5 micrograms/kg body weight, given subcutaneously once every day. There was no significant change in plasma SLI levels after bolus injection of GHRH(1-29)-NH2 before and during GHRH(1-29)-NH2 therapy. However, plasma SLI rose in basal plasma and nocturnal sleep after 3 months of GHRH(1-29)-NH2 therapy and remained the same during 6 months of treatment with GHRH(1-29)-NH2. The reason for this finding is uncertain, but an increase in SLI release from the enteroinsular axis is a possible explanation. The association of our findings with the role of the circulating SLI on nutrient homeostasis and the effects of GNRH on growth velocity is discussed.     

Synthesis and structure-activity relationship of 2-(aminoalkyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives: a novel series of 5-HT(2A/2C) receptor antagonists. Part 2.

Following the programme started at Janssen Research Foundation searching for 5-HT(2A/2C) antagonists, we now report on the synthesis of a series of substituted 2-(Dimethylaminomethyl)-2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepine derivatives. The 5-HT(2A), 5-HT(2C) and H(1) receptor affinities as well as the mCPP antagonistic activity of the compounds synthesised is described.     

Human enzyme polymorphism in the Canary Islands. III. Tenerife Island population

We analyzed the genetic polymorphism of eight red cell enzymes in samples from different geographical areas of Tenerife and the Iberian peninsula. The gene frequency heterogeneity found within the Tenerife samples was at the same level as that of Tenerife-mainland comparisons. The presence of the Negroid G6PD A+ allele in the Tenerife samples is evidence of an African admixture with a mean estimation of 4.5%.     

Detection and quantification of patulin and griseofulvin by high pressure liquid chromatography in different strains of Penicillium griseofulvum Dierckx

Patulin and griseofulvin production by twelve strains ofPenicillium griseofulvum Dierckx, eleven of which were isolated from pistachio (Pistacia vera) nuts and the other was supplied by the Spanish Collection of Type Culture, was investigated. Six strains of the eleven isolated had ability to produce patulin and griseofulvin in Yes medium. All the strains studied had no ability to produce patulin in Wickerham medium. Griseofulvin production was significant in both media but higher in Wickerham. These metabolites were separated and determined in the chloroform extracts of cultures by high performance liquid chromatography with ultraviolet detection. The best conditions were: acetonitrile — water (45∶55) as mobile phase, a flow rate of 2.0 mL/min and a μ Bondapack C₁₈ column.