Regulatory stimulus

We suspect that other characteristics of the regulatory stimulus not investigated here in detail or systematically are also important for technological change. They include the stringency of the regulatory demands, the time period allowed for the com-... 

Figure 25-8. Control of adipose tissue lipolysis. (TSH, thyroid-stimulating hormone FFA, free fatty acids.) Note the cascade sequence of reactions affording amplification at each step. The lipolytic stimulus is "switched off" by removal of the stimulating hormone the action of lipase phosphatase the inhibition of the lipase and adenylyl cyclase by high concentrations of FFA the inhibition of adenylyl cyclase by adenosine and the removal of cAMP by the action of phosphodiesterase. ACTFI,TSFI, and glucagon may not activate adenylyl cyclase in vivo, since the concentration of each hormone required in vitro is much higher than is found in the circulation. Positive ( ) and negative ( ) regulatory effects are represented by broken lines and substrate flow by solid lines.

For a skeletal element to respond to its mechanical environment, the cells in the tissue must regulate their environment in response to the mechanical stimuli they receive. The regulatory process can be thought of as a feedback loop (Figure 7.5) in which the osteocyte senses the stimulus and... 

Other methods include detection of production of mRNA or protein in response to the presence of the substrate (substrate-induced gene-expression screening). The success of this method is dependent on the retention of native upstream regulatory regions of genes in the clones which can switch on production of mRNA or enzyme in response to the stimulus of the presence of substrate. The method is used in screening libraries derived by random ... 

From a regulatory point of view, CaM kinase II is of particular interest as it has the characteristic of an enzyme with a built-in memory switch". The memory allows the CaM kinase to conserve a stimulatory signal over a longer period of time and to remain in an activated state, even when the initiating stimulus has died away. 

First, I contend that regulation and innovation are both primary responses to a need stimulus, but only rarely to each other. Because we install the regulatory response so quickly, we block out the slower innovative response as having the same cause. 

Every protein has specialized functions, and specific regulatory mechanisms often control transcription of its genes. A cell must respond to a large number of stimuli, and responses often include activation or repression of transcription.4153 In some cases an internal signal, such as a change in concentration of a nutrient or a key metabolite, provides the stimulus. In other cases an external stimulus such as heat or light is the inducer. A few examples follow. Others are mentioned throughout the book. 

The Jacob-Monod operon hypothesis has provided a tremendous stimulus for investigations directed toward understanding not only the lac system but other genetic regulatory systems as well. 

The terminal amino acids are under strict metabolic control. Some act as feedback inhibitors or repressors. Their synthesis is in equilibrium with metabolic requirement. This equilibrium position prevents their accumulation and hence the yield of these compounds is low. By changing the growth requirement (environmental stimulus) or by genetic manipulation, mutants could be found with limited or removed feedback inhibitors and repressors, e.g. auxotrophic and regulatory mutants 49). This needed a better understanding of biosynthesis and regulation of amino acid production. By selection of these mutants it became possible to alter microbial metabolism which led to the accumulation of the desired amino acids. 

The Lundh test also includes intestinal intubation and direct measurement of enzyme output in duodenal juice but uses a standardized test meal as a pancreatic stimulus. Because this test requires release of physiological regulatory mediators from the duodenal mucosa, it is less specific than the SC test and may render falsepositive results in intestinal diseases such as celiac sprue. 

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