Metabolic Synergy Research Articles

The importance of “first-blood circulation stage”, a new insight into the pathogenesis of clinical manifestations of preeclampsia

The tested hypothesis points out that exposure to environmental toxic substances originating from coal or other fossil fuels burning is the most decisive for the impacts of the metabolic synergy of nitrogen oxides as oxidants that cause hemoglobin oxidation to methemoglobin, and sulphur dioxide metabolites as inhibitors of antioxidants, in the bloodstream throughout the period of pregnancy. The main difference between the present three-stage hypothesis and other hypotheses is the assertion that, in the pathogenesis of early and late complicated pregnancy, methemoglobin takes on an important role. Methemoglobin by itself and from heme, redox-active ferric iron as a product of methemoglobin catabolism, has prooxidant properties and causes important structural and functional changes in the vascular endothelium, such as growth arrest, senescence, morphological alterations and cell apoptosis. Our own prospective study of methemoglobin in pregnancy revealed a significant rise and correlation between the ground level of SO2 and the level of methemoglobin: >1.5 g/L (r = 0.72, p 2, NOx, NO, NO2 and others) and that is an early biomarker of the identification of women with a pregnancy risk, and having an significant role upon adverse effects on mother and fetus health.

Synergistic metabolism in hybrid corn indicates bottlenecks in the carotenoid pathway and leads to the accumulation of extraordinary levels of the nutritionally important carotenoid zeaxanthin

Lutein and zeaxanthin cannot be synthesized de novo in humans, and although lutein is abundant in fruit and vegetables, good dietary sources of zeaxanthin are scarce. Certain corn varieties provide adequate amounts because the ratio of endosperm β:ε lycopene cyclase activity favours the β-carotene/zeaxanthin branch of the carotenoid pathway. We previously described a transgenic corn line expressing the early enzymes in the pathway (including lycopene β-cyclase) and therefore accumulating extraordinary levels of β-carotene. Here, we demonstrate that introgressing the transgenic mini-pathway into wild-type yellow endosperm varieties gives rise to hybrids in which the β:ε ratio is altered additively. Where the β:ε ratio in the genetic background is high, introgression of the mini-pathway allows zeaxanthin production at an unprecedented 56 μg/g dry weight. This result shows that metabolic synergy between endogenous and heterologous pathways can be used to enhance the levels of nutritionally important metabolites.

Emergent cooperation in microbial metabolism

Mixed microbial communities exhibit emergent biochemical properties not found in clonal monocultures. We report a new type of synthetic genetic interaction, synthetic mutualism in trans (SMIT), in which certain pairs of auxotrophic Escherichia coli mutants complement one another's growth by cross-feeding essential metabolites. We find significant metabolic synergy in 17% of 1035 such pairs tested, with SMIT partners identified throughout the metabolic network. Cooperative phenotypes show more growth on average by aiding the proliferation of their conjugate partner, thereby expanding the source of their own essential metabolites. We construct a quantitative, predictive, framework for describing SMIT interactions as governed by stoichiometric models of the metabolic networks of the interacting strains.

In vivo chondroprotection and metabolic synergy of glucosamine and chondroitin sulfate.

Supplements of glucosamine hydrochloride, low molecular weight chondroitin sulfate, and manganese ascorbate were tested separately and in combination for their ability to retard progression of cartilage degeneration in a rabbit instability model of osteoarthrosis. Computerized quantitative histologic evaluation of safranin O stained sections of the medial femoral condyles measured the grade and extent of tissue involvement of lesions. Severe lesions (Mankin grade greater than 7) were absent in all animals supplemented with a dietary mixture of glucosamine, chondroitin sulfate, and manganese ascorbate. Total linear involvement (mm of lesioned surface) and total grade (mean grade x number of lesions per animal) were reduced significantly in animals given the combination compared with controls (59% and 74% respectively). Animals supplemented with glucosamine, chondroitin sulfate, or manganese ascorbate alone had less moderate and severe tissue involvement than controls but not to the extent of the combined group. In vitro, a combination of glucosamine hydrochloride and chondroitin sulfate acted synergistically in stimulating glycosaminoglycan synthesis (96.6%). Chondroitin sulfate and manganese ascorbate but not glucosamine were effective in inhibiting degradative enzyme activity. These data suggest that the disease modifying effect (the ability to retard progression of cartilage degeneration) of a mixture of glucosamine, chondroitin sulfate, and manganese ascorbate is more efficacious than either agent alone.

MODELLING SYNERGISTIC EFFECTS OF TWO TOXIC AGENTS IN THE HONEYBEE

In previous experiments, a synergistic lethal effect on the honeybee has been demonstrated with two toxic agents: deltamethrin and prochloraz. The toxic agents were applied simultaneously or sequentially. Deltamethrin is metabolized by esterase and by cytochrome P-450-dependent monooxygenase. Prochloraz is a potent competitive inhibitor of cytochrome P-450. An attractive hypothesis explaining this synergic toxicity is that the persistence of deltamethrin is due to inhibition of the oxidative metabolism of deltamethrin by prochloraz. We tested this hypothesis using a mathematical model. A compartmental model in continuous time was constructed to represent this synergy by analyzing the degradation of toxic agents. This pharmacokinetic model was based on differential equations, using numerical resolution and Runge-Kutta’s integration method. When applied to a mixture of toxic agents, this model implies that the cumulative mortality of both compounds might be delayed compared to the mortality from treatment with toxic agents used separately. The hypothesis of metabolic synergy is compatible with experimental data only if the half-life of deltamethrin is short. The data from the model and the experimental data, diverged when deltamethrin was administered before prochloraz, which suggests that the phenomenon is more complex than expected.