Negative feedback network

Overproduction of E (isoleucine) inhibits enzyme E6 (threonine deaminase), and the consequent rise of D (threonine) reduces the rate of production of C (homoserine) via enzyme E3 (homoserine dehydrogenase). The concentration of B (aspartate semialdehyde) rises, and this in turn inhibits Ej (aspartokinase). It is therefore obvious why the control system is called a negative feedback network, or sequential feedback system. 

Because biomagnification and other transport processes take time, the harmful effect of many compoimds may not become evident for decades. This makes direct causal relationships between specific pollutants and environmental change difficult to establish. Substantiating such relationships is further complicated by the complex network of positive and negative feedbacks that occur among most parts of the crustal-ocean-atmosphere fectory. 

In recent years, work by Loomis and co-workers has raised the possibility that cAMP oscillations in D. discoideum may originate from an intracellular regulatory network rather than from the mixed positive and negative feedback exerted by extracellular cAMP [84, 85]. These authors obtained evidence for an intracellular feedback loop involving MAP kinase and the cAMP-dependent protein kinase, PKA. The later enzyme would inactivate adenylate cyclase after a cAMP pulse. Numerical simulations of a model based on this intracellular negative feedback loop confirm that it can produce sustained oscillations of cAMP. 

Signal transduction pathways and protein regulatory networks are not linear (26) but contain branches, negative feedback loops, and common points of connection between seemingly parallel pathways known as nodes. Furthermore, these pathways and networks are tightly controlled within cells so that disruption of any point has a rippling effect often activating compensatory mechanisms... 

The operational amplifier or in short, op-amp, is used so extensively in modem electronic circuits that it is called a panacea. Op-amps are always used with negative feedback so that the circuits are essentially determined by the feedback networks only. Within certain limits, the characteristics of the op-amps can often be neglected (Fig. H.2). 

It is not clear how this network is reprogrammed on activation of the p53 protein. Possibly, the DNA-damage-induced phosphorylation of p53 interferes with its interaction with the MDM2 protein, which leads to attenuation of the negative feedback loop. 

Mees, A.I. P.E. Rapp. 1978. Periodic metabolic systems Oscillations in multiple-loop negative feedback biochemical control networks. J. Math. Biol. 5 99-114. 

Chemical reaction network is a typical example of complexity, where the reactants can interact in a variety of ways depending on the nature of interaction (chemical as well as non-chemical). Oscillatory reactions involve a number of steps, including positive and negative feedbacks. The complexity leads to periodic as well as aperiodic oscillations (multi-periodic, bursting/intermittency sequential oscillations separated by a time pause, relaxation and chaotic oscillations). The mechanism is usually determined by non-linear kinetics and computer modelling. Once the reaction mechanism has been postulated, the non-linear time-dependent kinetic equation can be formulated in terms of concentrations of different reactants, which would yield a multi-variable equation. Delay differential equations are sometimes used to characterize oscillatory behaviour as in economics (Chapter 14). 

One of the few successful attempts, by investigators other than Clarke, to utilize stochastic network analysis was carried out by Eiswirth et al. (1991), who divide the known mechanisms of chemical oscillators into four categories two based on the positive feedback loop, and a threefold division of one of these according to the negative feedback loop. The structure of the classification scheme resembles somewhat the results of the approach described in section 5.4.2, but the analysis is considerably more detailed and rigorous. 

Without the capacitor network, the inverted signal fed back to the base directly would give us negative feedback. However, we will now delay it 180°, which is called a "phase shift." Then we will have delayed negative feedback. 

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