Insensitive Feedback

As is clear in this chapter, the recycling of plastics waste has increasingly been accepted as a response to a complex situation and the default understanding of this situation has not led to adequate action. However, despite the accepted value and ease of recycling plastics waste, most individuals have a great deal of difficulty in systemically recycling waste. 

In addition, it has been found that solid waste processes are insensitive to feedback and underestimate time lags between actions and responses. This insensitivity to feedback reflects a failure of the decision-making process to correctly assess the nature and significance of the solid waste management system, particularly the link between the decision and the environment. 

Solid waste management personnel have been astonished by how hard it is for firms to repeat their success when technology or markets change. For instance, no leading plastics manufacturer has been able to replicate its initial success when more advanced technologies were developed and their corresponding markets emerged. 

The failure of solid waste management can sometimes be ascribed to managerial myopia or organisation lethargy, or to insufficient resources or expertise. Many developed countries have great 

Solid waste management involves the manner in which waste is transformed into materials, innovation, technology, information, products or services. Here, innovation refers to a change in technology and technology refers to how an organisation transforms labour, capital and materials [14]. 

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S-(2-Aminoethyl)-L-cysteine (AEC), H2N-CH2-CH2-S-CH2-CH(NH2)-COOH, a lysine analog, acts as a false feedback inhibitor on aspartokinase, which produces aspartylphosphate from aspartate. The inhibitor simulates, for aspartokinase, the absence of lysine and threonine, and as a consequence the AEC insensitive mutant is no longer inhibited by lysine and threonine. The result was a yield increase from 0 to 16 g L 1. 

This feedback mechanism serves to make the radical number densities in the lower troposphere insensitive to the inclusion or exclusion of HNO rainout and to the resulting variations in n(HNO ) [Levy (154)]. With increasing altitude, this all breaks down as R33 becomes a more important path than R35, owing to the difference in activation energies. 

Hormones are molecules organisms use to convey information between cells. When target cells are distant from the hormone-producing cell, such molecules are called endocrine hormones. To ensure proper control of metabolism, the synthesis and secretion of many mammalian hormones are regulated by a complex cascade mechanism ultimately controlled by the central nervous system. In addition, a negative feedback mechanism precisely controls various hormone syntheses. A variety of diseases are caused by either overproduction or underproduction of a specific hormone or by the insensitivity of target cells. 

The pathway of biosynthesis of L-lysine and L-threonine in Corynebacterium glutamicum is shown in Fig. 1. The first step, the formation of phosphoaspartate from aspartate, is catalyzed by aspertokinase and this enzyme is susceptible to the concerted feedback inhibition by L-lysine and L-threonine. The auxotrophic mutant of homoserine (or threonine plus methionine), lacking homoserine dehydrogenase, was constructed and found to produce L-lysine in the culture medium. Second, the mutants which show the threonine or methionine sensitive phenotype caused by the mutation on homoserine dehydrogenase (low activity) was also found to produce appreciable amounts of L-lysine in the culture medium. Furthermore, a lysine analogue (S-aminoethylcysteine) resistant mutant was obtained as an L-lysine producer and in this strain aspartokinase was insensitive to the feedback inhibition. 

Recombinant DNA techniques were employed to improve the L-threonine producer. A threonine-deficient mutant of E. coli was transformed by the genes of threonine operon obtained from a-amino-/ -hydroxyvaleric acid (AHV)-resistant and feedback-insensitive mutants to amplify the expression of enzymes and to increase the amount of L-threonine. E. coli mutant strain was also constructed to have amplified genes of threonine operon obtained from AHV-resistant and feedback-insensitive mutant by the action of Mu phage on the chromosomal DNA. This strain is used in France in the practical production of L-threonine. The productivity of bacterial strains developed as the L-threonine producer is summarized in Table 2 [14]. L-Threonine hyperproducing E. coli mutant, which can produce 100 g/1 of L-threonine in 77 h, was constructed by Okamoto et al. who suggested that the strain has some impairment in L-threo-nine uptake function [15]. 

Trp (43), while AS is inhibited by Tip (43). ° As such, CM and AS are thought to participate in helping control carbon flux between Phe (1)/Tyr (2) and Trp (43) pathways in the chloroplast/plastid. Again, feedback-insensitive forms have been identified for CM and AS in the cytosoF " but the physiological significance is unknown. 

Comprehensive studies are now required, however, to determine the feedback properties of all of the enzymes leading to Phe (1)/Tyr (2) biosynthesis, including the individual Arabidopsis ADTs and the yet to be provisionally identified aminotransferases both in vivo and in vitro. This is a particularly interesting and important question, considering that feedback-insensitive isoforms exist for the other branch point enzymes DAHP synthase, CM, and AS. 

Sabine, J. R., Abraham, S. and Chaikoff, I. L., Control of hpid metabolism in hepatomas insensitivity of rate of fatty acid and cholesterol synthesis by mouse hepatoma BW7756 to fasting and to feedback control. Cancer Res 27 (1967) 793-799. 

On the other hand, feedback control is rather insensitive to all three of these drawbacks but has poor performance for a number of systems (multicapacity, dead time, etc.) and raises questions of closed-loop stability. Table 21.1 summarizes the relative advantages and disadvantages of the two control systems. 

We would expect that a combined feedforward-feedback control system will retain the superior performance of the first and the insensitivity of the second to uncertainties and inaccuracies. Indeed, any deviations caused by the various weaknesses of the feedforward control will be corrected by the feedback controller. This is possible because a feedback control loop directly monitors the behavior of the controlled process (measures process output). Figure 21.7 shows the configuration of a combined feedforward-feedback control system. 

PRPP is an important intermediate in the de novo synthesis of purines pathway (Figure 22.4). Defects in PRPP synthetase may render it insensitive to feedback inhibition by purine nucleotides. Thus, purine nucleotides are overproduced, leading to excessive uric acid synthesis and gout (Figure 22.9). 

TS levels are finely controlled by an autoregulatory feedback mechanism wherein unbound TS inhibits the translational efficiency of its own mRNA. When TS is bound to FdUMP, inhibition of translation is relieved, and levels of free TS are restored. Thus, TS autoregulation may be an important mechanism by which malignant cells become insensitive to the effects of 5-FU. 

Fig. 9.5. Scheme of the model considered for signal-induced, intracellular Ca" oscillations based on Ca Mnduced release (CICR). The stimulus (S) acting on a cell surface receptor (R) triggers the synthesis of IP3 the latter intracellular messenger elicits the release of Cif from an IPj-sensitive store (X, concentration X) at a rate proportional to the saturation function (B) of the IP3 receptor. Fast replenishment of X could involve activation of Ca" uptake from the extracellular medium into the IPj-sensitive store. Cytosolic Ca (Z, concentration Z) is pumped into an IPj-insensitive intracellular store Ca in the latter store (Y, concentration Y) is released into the cytosol in a process activated by cytosolic Ca ". This feedback, known as CICR, plays a primary role in the origin of Ca " oscillations. In its minimal version, the model contains only two variables, i.e. Y and Z, as X is treated as constant owing to fast replenishment of the IPj-sensitive Ca pool (Dupont et ai, 1991). 

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