Metabolite repression

Enzyme repression Mechanism by which the presence of a particular metabolite represses the genes coding for enzymes used in its synthesis. 

Microorganisms exhibit nutritional preferences. The enzymes for common substrates such as glucose are usually constitutive, as are the enzymes for common or essential metabohc pathways. Furthermore, the synthesis of enzymes for attack on less common substrates such as lactose is repressed by the presence of appreciable amounts of common substrates or metabolites. This is logical for cells to consei ve their resources for enzyme synthesis as long as their usual substrates are readily available. If presented with mixed substrates, those that are in the main metabolic pathways are consumed first, while the other substrates are consumed later after the common substrates are depleted. This results in diauxic behavior. A diauxic growth cui ve exhibits an intermediate growth plateau while the enzymes needed for the uncommon substrates are synthesized (see Fig. 24-2). There may also be preferences for the less common substrates such that a mixture shows a sequence of each being exhausted before the start of metabolism of the next. 

Microbial activity can also be stimulated by mineral colloids through their ability to sorb metabolites that would otherwise have an adverse effect on microbial growth (Filip et al. 1972 Filip and Hattori 1984) This may be due to the toxicity of metabolites, and their feed back repression and, encouraging competitors. Predictably, montmorillonite (CEC —100 cmol kg-1 and specific surface of 800 m g 1) is more effective than kaolinite and finely ground quarts. Other substances, such as antibiotics and pesticides that are toxic to some microorganisms, can also be adsorbed by the surfaces of mineral colloids (Theng and Orchard 1995 Dec et al. 2002). 

Inducible or repressible refers to the type of response the system makes to the presence of a metabolite. Inducible genes are turned on when they sense the presence of a metabolite. Usually, this means that the metabolite is a precursor of something the cell needs. If the precusor is present, inducible genes are turned on to metabolize it. Repressible genes are turned off by the presence of a metabolite. These genes are usually involved in the synthesis of the metabolite. If the cell has enough of the metabolite, the pathway is turned off (repressed). If the metabolite is not present, the pathway is turned on. 

The nematode species of most interest for the control of crop insect pests are from the genera Steinernema and Heterorhabditis, both characterised by their association with bacteria from the genera Xenorhabdus and Photorhabdus. These nematodes invade the insect and then release their symbiotic bacteria into the insect s haemocoel. The nematodes release metabolites that repress the immune system of the insect, allowing the bacteria to develop. The bacteria then release toxins that kill the insect within two to three days and also produce antibiotics that prevent the invasion of the dead insect by other bacteria. These bacteria then invade the entire insect cadaver and the nematodes subsequently begin to consume the bacteria. 

Some enzymes and carriers are synthesized only in response to the presence of the sugar, or of a structurally similar compound these enzymes and carriers are said to be inducible. Contrariwise, enzyme synthesis may be repressed by an increase in the concentration of ATP, or of some other metabolite. Induction and repression of enzymes and carriers provide two important kinds of control in metabolic regulation. 

Figure 11-1 Some control elements for metabolic reactions. Throughout the book modulation of the activity of an enzyme by allosteric effectors or of transcription and translation of genes is indicated by dotted lines from the appropriate metabolite. The lines terminate in a minus sign for inhibition or repression and in a plus sign for activation or derepression. Circles indicate direct effects on enzymes, while boxes indicate repression or induction of enzyme synthesis.

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. 

Cell line selection is one of the traditional and effective approaches to enhancing metabolite accumulation, and biochemical studies provide the fundamental information for the intentional regulation of secondary metabolism in plant cells. In a carrot suspension culture regulated by 2,4-dichlorophenoxyace-tic acid, Ozeki et al. [7] found that there was a correlation between anthocyanin synthesis and morphological differentiation for somatic embryogenesis they also demonstrated the induction and repression of phenylalanine ammonia lyase (PAL) and chalcone synthase correlated with formation of the respective mRNAs. Two biosynthetic enzymes, i. e., PAL and 3-hydroxymethylglutaryl-CoA reductase, were also related with shikonin formation in Lithospermum erythro-rhizon cultures [8]. 

As noted earlier, the velocity of any enzyme-catalyzed reaction is dependent upon the amount of effective enzyme present. Enzyme biosynthesis, like that of all proteins, is under genetic control, a long-term process. Biosynthesis of enzymes may be increased or decreased at the genome level. Various hormones can activate or repress the mechanisms controlling gene expression. Enzyme levels are the result of the balance between synthesis and degradation. This enzyme turnover may be altered by diverse physiological conditions, by hormone effects, and by the level of metabolites. 

In end-product repression (see later), it was postulated that the repressor protein is inactive until it binds the repressing metabolite (corepressor) to form an active repressor-corepressor complex that can combine with the operator gene to block synthesis at the operon. 

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