Regulatory circuits

The regulation of NCR-sensitive amino acid transporters in Saccharomyces cerevisiae has many points in common with that of catabolic enzymes. Amino acid permeases, as well as some other transporters of nitrogenous nutrients, are integrated into the regulatory circuits, both general and specific, which control catabolic processes. 

Nurse Even if it was one gene you could set up the system so that it would have limited variability. It would depend on the numbers of molecules involved in that circuit. You can devise limited variability in different ways. One is by having many different elements in the way that you have described, but you can also do it by having lots of molecules involved in a single regulatory circuit, which would reduce variability. 

Manipulation of one enzymatic step in a system can have wide reaching consequences because of the interplay between metabolite levels and a wide range of regulatory circuits. These circuits can operate at the level of transcription, translation, post-translational modification, or through allosteric and competitive influences on the kinetic properties of enzymes. 

The ultradian sleep—wake and temperature rhythm produced by 3rd ventricle infusion of TGFa closely resembles the effect of a focal excitotoxic lesion of SPZ neurons (Lu et al 2001). This ultradian rhythm is normally suppressed by circadian control and is disinhibited when SPZ neurons fail to relay SCN circadian information to sleep—wake circuits. Our results indicate that chronic TGFa administration uncouples SPZ neurons from sleep-regulatory circuits and that SPZ neurons expressing the EGFR transmit circadian information from the SCN to sleep—wake centres, in addition to likely regulating circadian locomotor activity. 

Protein-DNA binding interactions are the basis of the intricate regulatory circuits fundamental to gene function. We now turn to a closer examination of these gene regulatory schemes, first in prokaryotic, then in eukaryotic systems. 

Operons that produce the enzymes of amino acid synthesis have a regulatory circuit called attenuation, which uses a transcription termination site (the attenuator) in the mRNA. Formation of the attenuator is modulated by a mechanism that couples transcription and translation while responding to small changes in amino acid concentration. 

The complexity of regulatory circuits in eukaryotic cells is extraordinary as the following discussion shows. We conclude the section with an illustrated description of one of the most elaborate circuits the regulatory cascade that controls development in fruit flies. 

FIGURE 28-37 Regulatory circuits of the anterior-posterior axis in a Drosophila egg. The bicoid and nanos mRNAs are localized near the anterior and posterior poles, respectively. The caudal, hunchback, and pumilio mRNAs are distributed throughout the egg cytoplasm. The gradients of Bicoid (Bed) and Nanos proteins lead to accumulation of Hunchback protein in the anterior and Caudal protein in the posterior of the egg. Because Pumilio protein requires Nanos protein for its activity as a translational repressor of hunchback, it functions only at the posterior end. 

Preliminary experiments done in our laboratory showed that antibodies specific for cellobiohydrolase failed to cross react with either purified cellobiase, purified endoglucanase, or crude endoglucanase. These results, together with data reported in the literature, which show that endoglucanase and cellobiohydrolase have different physical structures, indicate that the three cellulases could be transcribed and translated by different genomes. In this context, then, the question arises as to whether cellulase production is regulated by a common regulatory circuit or by different circuits. 

Bernhardt C, Zhao M, Gonzalez A, Lloyd A, Schiefelbein J. 2005. The bHLH genes GL3 and EGL3 participate in an intercellular regulatory circuit that controls cell patterning in the Arabidopsis root epidermis. Development 132 291-298. 

In addition to the obvious deactivating role of deiodinases, there has been recent evidence that a relationship exists between regulation of deiodination of thyroid hormones in target cells and the intracellular effects of T4 and T3 on pituitary and hypothalamus function. In the rat pituitary, and probably the human, type-II deiodinase-catalyzed conversion of T4 to T3 is a prerequisite for inhibition of TRH release. rT3, produced from T4 by type-III deiodinase, is a potent inhibitor of type-II deiodinase. In a postulated regulatory circuit, rT3 formed from T4 by type-III deiodinase in surrounding CNS (Central Nervous System) tissue enters the pituitary and inhibits type-II enzyme. The resulting decrease in T3 concentration, in turn, causes an increase in TSH secretion49. 

K. Yoshida, Z. Kuromitsu, N. Ogawa, K. Ogawa and Y. Oshima (1987). Regulatory circuit for phosphatase synthersis in Saccharomyces cerevisiae. In Phosphate metabolism and cellular regulation in microorganisms. Washington, Amer. Soc. Microbiol., pp. 49-55. 

Henze MW, Kuhn LC (1996) Molecular control of vertebrate iron metabolism mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress. Proc Natl Acad Sci USA 93 8175-8182... 

Such regulatory circuits include both positive (e.g. TRH, TSH) and negative (e.g. T4, T3) components. A faU in T4/T3 levels causes a positive feedback and increase in TRH and TSH synthesis once T4/T3 levels are restored to a new steady state, negative feedback suppresses TRH and TSH. 

Thus, it appears that the activating effect exerted by the benzodiazepine alkaloids rests on a specific property of the primary metabolic enzymes involved in the biosynthesis of benzodiazepine precursors and present during the phase of alkaloid formation. If this effect would also occur in vivo (as suggested by the above characteristics), it would serve the coordination of precursor (and alkaloid) biosynthesis within a far-reaching feedback mechanism. Such a regulatory circuit... 

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