Regulating gene transcription conserves energy

As a normal inhabitant of the human intestine, E. coli must be able to adjust to sudden changes in its chemical environment. Its host may present it with one foodstuff one hour (e.g., glucose in fruit) and another the next (e.g., lactose in milk). Such changes in nutrients present the bacterium with a metabolic challenge. Glucose is its preferred energy source, and is the easiest sugar to metabolize. Lactose is a β-galactoside—a disaccharide containing galactose β-linked to glucose (see Key Concept 3.3). Three proteins are involved in the initial uptake and metabolism of lactose by E. coli:

  1. β-Galactoside permease is a carrier protein in the bacterial cell membrane that moves the sugar into the cell.

  2. β-Galactosidase is an enzyme that hydrolyses lactose to glucose and galactose.

  3. β-Galactoside transacetylase transfers acetyl groups from acetyl CoA to certain β-galactosides. Its role in the metabolism of lactose is not clear.

When E. coli grows and reproduces in a lab medium that contains glucose but no lactose or other β-galactosides, the levels of these three proteins are extremely low—the cell does not waste energy and materials making the unneeded enzymes. But if the environment changes such that lactose is the predominant sugar available and very little glucose is present, the bacterium promptly begins making all three enzymes after a short lag period. While few molecules of β-galactosidase are present in an E. coli cell in the presence of glucose, in the absence of glucose the addition of lactose can induce the synthesis of about 1,500 times more molecules of β-galactosidase per cell (Figure 16.2A)!

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Figure 16.2 An Inducer Stimulates the Expression of a Gene for an Enzyme (A) When lactose is added to the growth medium for the bacterium E. coli, the synthesis of β-galactosidase begins only after an initial lag period. (B) There is a lag period because the mRNA for β-galactosidase has to be made before the protein can be made. The amount of mRNA decreases rapidly after the lactose is removed, indicating that transcription is no longer occurring. These changes in mRNA levels indicate that the mechanism of induction by lactose is transcriptional regulation.

What’s behind this dramatic increase? An important clue comes from measuring the amount of mRNA for β-galactosidase. The mRNA level increases during the lag period after lactose is added to the medium, and this mRNA is translated into protein (Figure 16.2B). Moreover, the high mRNA level depends on the presence of lactose, because if the lactose is removed, the mRNA level goes down. The response of the bacterial cell to lactose is clearly at the level of transcription.

Compounds such as lactose that stimulate the synthesis of a protein are called inducers. The proteins that are produced are called inducible proteins, whereas proteins that are made all the time at a constant rate are called constitutive proteins. (Think of the constitution of a country, a document that does not change under normal circumstances.)

We have now seen two basic ways of regulating the rate of a metabolic pathway. In Key Concept 8.5 we described the allosteric regulation of enzyme activity, which allows the rapid fine-tuning of metabolism. Regulation of protein synthesis—that is, regulation of the concentration of enzymes—is slower but results in greater savings of energy and resources. Protein synthesis is a highly endergonic process, since assembling mRNA, charging tRNA, and moving the ribosomes along mRNA all require the hydrolysis of nucleoside triphosphates such as ATP. Figure 16.3 compares these two modes of regulation.

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Figure 16.3 Two Ways to Regulate a Metabolic Pathway Feedback from the end product of a metabolic pathway can block enzyme activity (allosteric regulation), or it can stop the transcription of genes that code for the enzymes in the pathway (transcriptional regulation).