Lac+operon

=Lac operon=

The **lac operon** is a bacterial operon, originally discovered and characterised in //E. coli.// An **operon** is a cluster of genes that are transcribed simultaneously, from a single promoter region, into a monocistronic mRNA.

The lac operon includes a **coding region** containing three genes, each gene coding for a different protein required in lactose uptake and metabolism; an **operator sequence** upstream of the coding region which binds regulatory molecules, and a **promoter sequence** further upstream of the operator. As with all prokaryotic genes, the lac operon also ends with a terminator; the terminator lies //downstream// of the coding region.

Because all three genes can be switched on or off from the same operator sequence, this ensures tight regulation of the genes' expression in accordance with the demand for their products - i.e. according to how much lactose is available to be metabolised by the cell.

The three structural genes found in the coding region of the lac operon are:
 * //Lac Y// which encodes lactose permease, a membrane channel protein required for the import of lactose
 * //Lac Z// which encodes beta galactosidase, the enzyme which hydrolyses lactose to its monosaccharide constituents
 * //Lac A// which encodes transacetylase, an enzyme which acetylases other galactoside sugars so that the cell can focus on metabolising lactose exclusively

By default, the lac operon is switched 'off'. This is because a bacterium's preferred source of carbon and energy is glucose rather than lactose, so it would be energetically wasteful to continually synthesise the lactose-metabolising proteins.

Further upstream, though not directly adjacent, to the lac operon is another gene called **//lac I//**. //Lac I// is constitutively (always) expressed. The gene product of //Lac I// is a repressor molecule. The repressor molecule binds to the operator sequence of the lac operon, preventing RNA polymerase from binding to it and thereby inhibiting transcription of the lac operon genes. It is because of the constitutive expression of this repressor molecule that the lac operon is by default inactive.

When lactose is present in the cell, even in small concentrations, a compound called **allolactose** becomes available. Allolactose is an **inducer molecule**: it binds to the repressor molecule causing it to release from the operator sequence of the lac operon. Now RNA polymerase can access the lac operon and the structural genes are transcribed. Once transcribed and translated, the proteins are available to metabolise lactose. Once lactose has been metabolised and its concentration in the cell is once again depleted, the repressor molecule is no longer inhibited and can once again 'turn off' the lac operon. Because the lac operon is induced by the presence of lactose, it is described as an **inducible system**. The form of control described here is **negative control.**

However, the lac operon is also under **positive control**. In the absence of glucose uptake, a protein in the membrane called adenylate cyclase is phosphoprylated, leading to the synthesis of a messenger molecule called cyclic AMP (cAMP). cAMP binds to another protein called CRP to form a cAMP-CRP complex which, when bound to DNA, induces lac operon transcription by increasing the affinity of RNA polymerase to the promoter region, in spite of the presence of the repressor molecule. This means that when glucose supplies are depleted and the cell needs to turn to metabolising what lactose is available, it can. This process is called **catabolite repression**.