Pheromone deactivation catalyzed by receptor molecules: a quantitative kinetic model

A quantitative model of pheromone-receptor interaction and pheromone deactivation, the supposed rate-limiting processes underlying the receptor potential kinetics, is worked out for the moth Antheraea polyphemus. In this model, the pheromone interacts with the receptor molecule while bound to the reduced form of the pheromone binding protein. The receptor molecules--besides their receptor function-- catalyze the observed shift of the pheromone-binding protein from the reduced to the oxidized form (Ziegelberger, G., Eur. J. Biochem., 232, 706-711, 1995), which deactivates the pheromone bound to pheromone binding protein. With the following parameters, the model fits morphological, radiometric, electrophysiological and biochemical data: a maximum estimate of 1.7 x 10(7) receptor molecules/cell (with 40,000 units/micron 2 of receptor cell membrane), rate constants k1 = 0.2/(s.microM) for the association, k2 = 10/s for the dissociation of the ternary complex of binding protein, pheromone and receptor, and k3 = 10/s for the deactivation via the redox shift. With these parameters, the duration of elementary receptor potentials elicited by single pheromone molecules (approximately 50 ms) reflects the lifetime of the ternary complex, tau = 1/(k2 + k3). The receptor occupancy produced by the model for threshold stimuli fits the sensitivity of the receptor cell to single pheromone molecules.      

Effect of recombinant human growth hormone on urinary 15N-nitrogen balance in girls with Turner syndrome as compared to children with growth hormone deficiency

15N-nitrogen balances before and on human growth hormone (hGH) were studied in 13 girls with Turner syndrome (TS) aged 4.4-16 (median 13.2) years (45,X0 or equivalent, no X0/XX mosaicism, no estrogen replacement). The results were compared with those reported from 9 patients with growth hormone deficiency (GHD). The TS patients received subcutaneous hGH doses of 2 x 3 (group A, n = 6), 3 x 2 (group B, n = 3), or 2 x 6 (group C, n = 4) IU/m2 on consecutive days. The mean 15N dose given to the patients of groups A and C was higher (13.6 mg/kg) than that given to those of group B (2.7 mg/kg). The lower hGH doses in the first two groups induced small positive mean 15N balance changes (+0.6 +/- 0.6 mg/kg 15N, group A; +0.03 mg/kg, group B). The higher hGH dose in group C caused a more marked mean balance change (+3.0 mg/kg 15N) comparable to that in GHD patients (+3.2 mg/kg). Individual variation of response, however, was larger in patients with TS than in those with GHD. With low and high hGH doses, there were responders and nonresponders. It is concluded from this pilot study in a small number of cases that 15N balance studies might be potentially useful to choose the appropriate hGH dose for long-term treatment in TS patients.     

Using a logical model to predict the growth of yeast

Background  

A logical model of the known metabolic processes in S. cerevisiae was constructed from iFF708, an existing Flux Balance Analysis (FBA) model, and augmented with information from the KEGG online pathway database. The use of predicate logic as the knowledge representation for modelling enables an explicit representation of the structure of the metabolic network, and enables logical inference techniques to be used for model identification/improvement.     

Complexity of developmental control: analysis of embryonic cell lineage specification in Caenorhabditis elegans using pes-1 as an early marker.

In the early Caenorhabditis elegans embryo five somatic founder cells are born during the first cleavages. The first of these founder cells, named AB, gives rise to 389 of the 558 nuclei present in the hatching larva. Very few genes directly involved in the specification of the AB lineage have been identified so far. Here we describe a screen of a large collection of maternal-effect embryonic lethal mutations for their effect on the early expression of a pes-1::lacZ fusion gene. This fusion gene is expressed in a characteristic pattern in 14 of the 32 AB descendants present shortly after the initiation of gastrulation. Of the 37 mutations in 36 genes suspected to be required specifically during development, 12 alter the expression of the pes-1::lacZ marker construct. The gene expression pattern alterations are of four types: reduction of expression, variable expression, ectopic expression in addition to the normal pattern, and reduction of the normal pattern together with ectopic expression. We estimate that approximately 100 maternal functions are required to establish the pes-1 expression pattern in the early embryo.     

Flux detectors versus concentration detectors: two types of chemoreceptors

Dose-response curves relating the external stimulus concentration to receptor occupancy differ in two types of chemoreceptor organs. In 'concentration detectors' the receptor molecules at the receptor cell membrane are directly exposed to the external stimulus concentration; these organs exhibit the well-known hyperbolic dose-response relationship reflecting the association-dissociation of stimulus and receptor molecules. In contrast, 'flux detectors' accumulate the stimulus molecules in a perireceptor compartment. In flux detectors, deactivation of stimulus molecules may be in balance with arrival, as a prerequisite for producing a constant effective stimulus concentration at constant adsorptive flux of stimulus molecules. In a simple model of a flux detector in which receptor molecules themselves catalyze the deactivation, the dose-response relationship is linear. It reflects the rate of stimulus deactivation. If the deactivation is catalyzed by a separate enzyme, the dose-response relationship can be close to hyperbolic, or linear. In all cases, the receptor molecules are maximally occupied if the adsorptive flux equals or exceeds the maximum rate of stimulus deactivation. The time course of the receptor potential recorded from moths' pheromone receptors depends on the odor compound, which suggests that a peripheral process, possibly the stimulus deactivation, is the slowest, rate-limiting process of the transduction cascade. Further evidence comes from experiments with stimuli oversaturating the mechanism responsible for the decline of the receptor potential.