Catabolite repression
Encyclopedia
Carbon catabolite repression, or simply catabolite repression, is an important part of global control system of various bacteria
and other micro-organisms. Catabolite repression allows bacteria to adapt quickly to a preferred (rapidly metabolisable) carbon and energy source first. This is usually achieved through inhibition
of synthesis of enzymes involved in catabolism
of carbon sources other than the preferred one. The catabolite repression was first shown to be initiated by glucose
and therefore sometimes referred to as the glucose effect. However, the term "glucose effect" is actually a misnomer
since other carbon sources are known to induce catabolite repression. Catabolite repression by the catabolite activator protein
is a well known example of a modulon
.
. E. coli grows faster on glucose than on any other carbon source. For example, if E. coli is placed on an agar plate
containing only glucose and lactose
, the bacteria will use glucose first and lactose second. When glucose is available in the environment, the synthesis of β-galactosidase is under repression due to the effect of catabolite repression caused by glucose. The catabolite repression in this case is achieved through the utilization of phosphotransferase system.
An important enzyme from the phosphotranferase system called Enzyme II A (EIIA) plays a central role in this mechanism. There are different catabolite-specific EIIA in a single cell, even though different bacterial groups have specificities to different sets of catabolites. In enteric bacteria one of the EIIA enzymes in their set is specific for glucose transport only. When glucose levels are high inside the bacteria, EIIA mostly exists in its unphosphorylated form. This leads to inhibition of adenylyl cyclase and lactose permease
, therefore cAMP
levels are low and lactose can not be transported inside the bacteria. After some time, the glucose is all used up and the second preferred carbon source (i.e. lactose) has to be used by bacteria. Absence of glucose will "turn off" catabolite repression.
Furthermore, when glucose levels are low the phosphorylated form of EIIA accumulates and consequently activates the enzyme adenylyl cyclase, which will produce high levels of cAMP
. cAMP binds to catabolite activator protein
(CAP) and together they will bind to a promoter sequence on the lac operon
. However, this is not enough for the lactose genes to be transcribed. Lactose must be present inside the cell to remove the lactose repressor
from the operator sequence (transcriptional regulation
). When these two conditions are satisfied, it means for the bacteria that glucose is absent and lactose is available. Next, bacteria start to transcribe lactose gene and produce β-galactosidase enzymes for lactose metabolism. The example above is a simplification of a complex process. Catabolite repression is considered to be a part of global control system and therefore it affects more genes rather than just lactose gene transcription.
Note that E. coli also has an alternative cAMP
independent catabolite repression mechanism that utilizes a protein called catabolite repressor activator (Cra). This same mechanism is also present in Gram positive bacteria such as Bacillus subtilis
, however it is called catabolite control protein A (CcpA
). In this alternative pathway CcpA negatively represses other sugar operons so they are off in the presence of glucose. It works by the fact that Hpr is phosphorylated by a specific mechanism, when glucose enters through the cell membrane protein EIIC, and when Hpr is phosphoralated it can then allow CcpA to block transcription of the alternative sugar pathway operons at their respective cre sequence binding sites.
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
and other micro-organisms. Catabolite repression allows bacteria to adapt quickly to a preferred (rapidly metabolisable) carbon and energy source first. This is usually achieved through inhibition
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
of synthesis of enzymes involved in catabolism
Catabolism
Catabolism is the set of metabolic pathways that break down molecules into smaller units and release energy. In catabolism, large molecules such as polysaccharides, lipids, nucleic acids and proteins are broken down into smaller units such as monosaccharides, fatty acids, nucleotides, and amino...
of carbon sources other than the preferred one. The catabolite repression was first shown to be initiated by glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
and therefore sometimes referred to as the glucose effect. However, the term "glucose effect" is actually a misnomer
Misnomer
A misnomer is a term which suggests an interpretation that is known to be untrue. Such incorrect terms sometimes derive their names because of the form, action, or origin of the subject becoming named popularly or widely referenced—long before their true natures were known.- Sources of misnomers...
since other carbon sources are known to induce catabolite repression. Catabolite repression by the catabolite activator protein
Catabolite Activator Protein
Catabolite Activator Protein or CAP is a transcriptional activator that exists as a homodimer in solution, with each subunit comprising a ligand-binding domain at the N-terminus , which is also responsible for the dimerization of the protein, and a DNA-binding domain at the C-terminus...
is a well known example of a modulon
Modulon
An operon is a set of genes controlled by a single DNA binding protein. Multiple operons controlled by the same repressor are grouped together as a regulon....
.
Example - Escherichia coli
Catabolite repression was extensively studied in Escherichia coliEscherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
. E. coli grows faster on glucose than on any other carbon source. For example, if E. coli is placed on an agar plate
Agar plate
An agar plate is a Petri dish that contains a growth medium used to culture microorganisms or small plants like the moss Physcomitrella patens.Selective growth compounds may also be added to the media, such as antibiotics....
containing only glucose and lactose
Lactose
Lactose is a disaccharide sugar that is found most notably in milk and is formed from galactose and glucose. Lactose makes up around 2~8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey. The name comes from or , the Latin word for milk,...
, the bacteria will use glucose first and lactose second. When glucose is available in the environment, the synthesis of β-galactosidase is under repression due to the effect of catabolite repression caused by glucose. The catabolite repression in this case is achieved through the utilization of phosphotransferase system.
An important enzyme from the phosphotranferase system called Enzyme II A (EIIA) plays a central role in this mechanism. There are different catabolite-specific EIIA in a single cell, even though different bacterial groups have specificities to different sets of catabolites. In enteric bacteria one of the EIIA enzymes in their set is specific for glucose transport only. When glucose levels are high inside the bacteria, EIIA mostly exists in its unphosphorylated form. This leads to inhibition of adenylyl cyclase and lactose permease
Permease
The permeases are membrane transport proteins, a class of multipass transmembrane proteins that facilitate the diffusion of a specific molecule in or out of the cell by passive transport...
, therefore cAMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
levels are low and lactose can not be transported inside the bacteria. After some time, the glucose is all used up and the second preferred carbon source (i.e. lactose) has to be used by bacteria. Absence of glucose will "turn off" catabolite repression.
Furthermore, when glucose levels are low the phosphorylated form of EIIA accumulates and consequently activates the enzyme adenylyl cyclase, which will produce high levels of cAMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
. cAMP binds to catabolite activator protein
Catabolite Activator Protein
Catabolite Activator Protein or CAP is a transcriptional activator that exists as a homodimer in solution, with each subunit comprising a ligand-binding domain at the N-terminus , which is also responsible for the dimerization of the protein, and a DNA-binding domain at the C-terminus...
(CAP) and together they will bind to a promoter sequence on the lac operon
Lac operon
The lac operon is an operon required for the transport and metabolism of lactose in Escherichia coli and some other enteric bacteria. It consists of three adjacent structural genes, lacZ, lacY and lacA. The lac operon is regulated by several factors including the availability of glucose and of...
. However, this is not enough for the lactose genes to be transcribed. Lactose must be present inside the cell to remove the lactose repressor
Repressor
In molecular genetics, a repressor is a DNA-binding protein that regulates the expression of one or more genes by binding to the operator and blocking the attachment of RNA polymerase to the promoter, thus preventing transcription of the genes. This blocking of expression is called...
from the operator sequence (transcriptional regulation
Transcriptional regulation
Transcriptional regulation is the change in gene expression levels by altering transcription rates. -Regulation of transcription:Regulation of transcription controls when transcription occurs and how much RNA is created...
). When these two conditions are satisfied, it means for the bacteria that glucose is absent and lactose is available. Next, bacteria start to transcribe lactose gene and produce β-galactosidase enzymes for lactose metabolism. The example above is a simplification of a complex process. Catabolite repression is considered to be a part of global control system and therefore it affects more genes rather than just lactose gene transcription.
Note that E. coli also has an alternative cAMP
Cyclic adenosine monophosphate
Cyclic adenosine monophosphate is a second messenger important in many biological processes...
independent catabolite repression mechanism that utilizes a protein called catabolite repressor activator (Cra). This same mechanism is also present in Gram positive bacteria such as Bacillus subtilis
Bacillus subtilis
Bacillus subtilis, known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium commonly found in soil. A member of the genus Bacillus, B. subtilis is rod-shaped, and has the ability to form a tough, protective endospore, allowing the organism to tolerate...
, however it is called catabolite control protein A (CcpA
CcpA
E-coli also has an alternative cAMP independent catabolite repression mechanism that utilizes a protein called catabolite repressor activator . This same mechanism is also present in Gram-positive bacteria such as Bacilus subtilis, however it is called catabolite control protein A...
). In this alternative pathway CcpA negatively represses other sugar operons so they are off in the presence of glucose. It works by the fact that Hpr is phosphorylated by a specific mechanism, when glucose enters through the cell membrane protein EIIC, and when Hpr is phosphoralated it can then allow CcpA to block transcription of the alternative sugar pathway operons at their respective cre sequence binding sites.
External links
- http://www.mun.ca/biochem/courses/4103/topics/catabintro.html
- http://pathmicro.med.sc.edu/mayer/geneticreg.htm