Genetic Control of Enzyme Synthesis

B. Genetic Control of Enzyme Synthesis 546 Box 11-A Cholera Toxin and Other Dangerous... 

Three mechanisms of cellular control over enzyme activity exist. One method involves the synthesis of enzyme precursors called zymogens, which are activated when needed by the ceU. The second mechanism relies on the binding of small molecules (modulators), which increase or decrease enzyme activity. Genetic control of enzyme synthesis, the third method, regulates the amount of enzyme available. 

Quantity of enzyme The enzyme concentration in cells is regulated at the synthetic level by genetic control, which may occur positively or negatively. Alternatively, the control can be exerted by the specihc degradative pathways. The genetic control of enzyme (protein) synthesis and specific protein degradation will be considered in the Chapters 12 and 13. 

One way to increase production from an enzyme-catalyzed reaction, given a sufficient supply of substrate, is for a cell to increase the number of enzyme molecules present. The synthesis of all proteins, including enzymes, is under genetic control by nucleic acids (Chapter 11). An example of the genetic control of enzyme activity involves enzyme induction, the synthesis of enzymes in response to a temporary need of the cell. 

Genetic control of enzyme activity means that a cell synthesizes an enzyme when conditions temporarily require it. Such a controlled synthesis is called enzyme induction. 

The molecular and genetic relationship between enzyme induction and repression was clarified by the genetic research of Jacob and Monod at the Pasteur Institute, Paris (see reference l7>). Their classic work led them to develop the operon hypothesis for the control of protein synthesis in prokaryotes, which has since been verified by direct biochemical experiments. 

What can be accomplished by protein turnover One benefit is the removal of proteins that have sustained spontaneous hydrolytic damage or oxidative damage. Another benefit is that protein turnover makes possible the control of enzyme levels by means of genetic regulation. In a condition where an increase in the acbvity of a parbcular enzyme is needed, the rale of transcripbon of the mRNA coding for the enzyme can be increased. This increase results in an increase in translation, that is, the synthesis of the protein s polypeptide chain. In a condition... 

The evidence suggested yeast adenylosuccinate synthetase catalyzed the first committed step in AMP biosynthesis and was also involved in the repression of synthesis of the early enzymes of the pathway. The mechanism by which this repression occurs remains unknown. Woods and co-workers (115,116) have isolated several prototrophic mutants of yeast defective in control of purine synthesis that are not allelic with adel2. Genetic analysis of these mutants suggested that the regulatory function of adenylosuccinate synthetase may be affected in conjunction with as many as three other gene products (116). 

Like other cells, a neuron has a nucleus with genetic DNA, although nerve cells cannot divide (replicate) after maturity, and a prominent nucleolus for ribosome synthesis. There are also mitochondria for energy supply as well as a smooth and a rough endoplasmic reticulum for lipid and protein synthesis, and a Golgi apparatus. These are all in a fluid cytosol (cytoplasm), containing enzymes for cell metabolism and NT synthesis and which is surrounded by a phospholipid plasma membrane, impermeable to ions and water-soluble substances. In order to cross the membrane, substances either have to be very lipid soluble or transported by special carrier proteins. It is also the site for NT receptors and the various ion channels important in the control of neuronal excitability. 

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