Repression of enzyme synthesis

Lipogenesis is regulated at the acetyl-CoA carboxylase step by allosteric modifiers, phosphorylation/de-phosphorylation, and induction and repression of enzyme synthesis. Citrate activates the enzyme, and long-chain acyl-CoA inhibits its activity. Insulin activates acetyl-CoA carboxylase whereas glucagon and epinephrine have opposite actions. 

The nature of the molecular defect Is unclear and presumably lies In the repression mechanism for the gene controlling formation of the enzyme protein. Exposure to any of the drugs listed In Table V results In further marked de-repressIon of enzyme synthesis and severe porphyria. 

DRUGS INDUCING MARKED DE-REPRESSION OF ENZYME SYNTHESIS... 

The regulatory mechanisms described above modify the activity of existing enzyme molecules. However, cells can also regulate the amount of enzyme present—usually by altering the rate of enzyme synthesis. The increased (induction) or decreased (repression) of enzyme synthesis leads to an alteration in the total population of active sites. [Note The efficiency of existing enzyme molecules is not affected.] Enzymes subject to regulation of synthesis are often those that are needed at only one stage of development or under selected... 

The flow of intermediates through metabolic pathways is controlled by 1bir mechanisms 1) the availability of substrates 2) allosteric activation and inhibition of enzymes 3) covalent modification of enzymes and 4) induction-repression of enzyme synthesis. This scheme may at first seem unnecessarily redundant however, each mechanism operates on a different timescale (Figure 24.1), and allows the body to adapt to a wde variety of physiologic situations. In the fed state, these regulatory mechanisms ensure that available nutrients are captured as glycogen, triacylglycerol, and protein. 

Reoviruses 248. See also front cover Repair systems 16 Replication cycle. See Cell cycle Repression of enzyme synthesis 536, 538, 539 Repressor(s) 76, 239... 

FIGURE 3.9.2 Inhibition of enzyme activity can be due to a high concentration of the product, or through direct inhibition of the product on the substrates, or through product repression of enzyme synthesis. 

Table 2. Differences between feedback inhibition and repression of enzyme synthesis.

Induction (derepression) and repression of enzyme synthesis by transcriptional regulation on the DNA template, or the RNA polymerase. 

Viral Action at the Level of Translation. It is known that in eukaryotic cells induction and repression of enzyme synthesis can occur at the level of messenger RNA (Tomkins and Martin, 1970). Thus, the SV40, polyoma, and Moloney sarcoma viruses could contain the genetic information for a common repressor molecule which could interfere with the synthesis of aminosugar transferase. Both DNA viruses can code for 5-10 polypeptides (Eckhart, 1969), and the potential coding capacity of the large RNA tumor viruses is extensive. 

Coarse control involves then, regulation by induction and repression of enzyme synthesis. Fine control involves regulation by activation and inhibition of enzy me activity. Other factors, such as availability of co-factors, will naturally also affect the rate of enzyme reactions (see p. 69). 

In other cases we encounter not induction but repression of enzyme synthesis by a metabolite in whose synthesis the enzyme is concerned (the same may also be inhibited in its activity by other components of the reaction sequence in which it it involved, see p. 252). The enzyme whose activity is lost or markedly reduced is not necessarily that which completes the synthesis of the repressor molecule (i.e. not that catalysing the last reaction of the biosynthetic pathway). For instance, uracil can suppress, in certain strains of the bacterium, Escherichia coU, the activity of the enzyme aspartate carbamyl-transferase which promotes the interaction between aspartic acid and carbamyl phosphate, a reaction which is the first step in the reaction sequence involved in pyrimidine biosynthesis. Further, the experimental evidence indicates that the uracil acts as a repressor by preventing synthesis of the enzyme. 

A second model (Fig. 9.7) can be based upon the concept of the role of structural and regulator genes in the induction and repression of enzyme synthesis (Chapter 8, p. 251) and involves two reaction sequences interconnected in that each produces an inducer of the other. The two systems, not necessarily otherwise closely related in metabolism (they could be involved in widely different metabolic systems), are mutually dependent. One system automatically induces the other by inactivating the appropriate repressor substance. If a metabolic pattern was the outcome of a number of reaction sequences interconnected in this way, a point activation... 

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