The lac Operon Explained [Updated]

Click to enlarge Photo: NIH 

The lac operon is a favorite of microbiology and biology textbooks, used to explain transcription, regulation, and catabolism. Here's my quick synopsis of the regulation involved, making sure the cell only transcribes genes that encode lactose-eating enzymes only when it is physiologically necessary. But first, a GENETICS crash course in biology:

An operon is a group of genes transcribed as a single unit. It's like buying Orange Box. There's five separate games, but they're all purchased at once in a neat box. The same thing with an operon. If the operon is ON, you get all of the genes activated. If the operon is OFF, none of the genes are activated.

RNA polymerase is a protein that reads DNA molecules in the cell to make RNA. This RNA is then read again by ribosomes to direct the synthesis of specific proteins..

The lac operon is just a string of DNA with two regulatory sites on the DNA and three structural genes (but we'll only talk about two here). The first of the two regulatory sites is the promoter, where the RNA polymerase binds to read the operon to make an RNA copy of it. The second regulatory site is called the operator, where the repressor binds to the operon. The promoter and operator overlap, so if the operator site is occupied by the repressor, RNA polymerase can't access the promoter to start reading the rest of the operon. Imagine the repressor and RNA polymerase as two brothers, and think of the operator and promoter sites as a chair that just big enough for one of two brothers to sit in. One of the brothers, the repressor, is lazy and if he sits in the chair he's going to nap. If the other brother, RNA polymerase, gets to sit in the chair, he's going to be productive and a ton of protein's going to be made. These brothers aren't going to share the chair; either the repressor or RNA polymerase sits in it, but not both. If the repressor binds to operator, the operon is in the OFF position. No genes in the operon are being transcribed, no proteins are being made in that operon. If RNA polymerase binds to the promoter, the operon is in the ON position, and the structural genes are being transcribed. What decides who gets the chair, then?

Turns out the lazy repressor brother is allergic to lactose, so if there's lactose around, he dies and RNA polymerase gets to sit in the chair. In the presence of lactose, the repressor is inactivated, and as a result, the RNA polymerase is free to bind to the promoter of the operon and begin transcription of lacZ and lacY genes, which will be subsequently translated into galactosidase and permease proteins, respectively. These proteins allow the cell to break down lactose and use it as an energy source. First, permease must to allow lactose to enter the cell. Then galactosidase is required to break down lactose, a two ring sugar, into galactose and glucose, both single ringed sugars. Both proteins are required if the cell is to use lactose effectively as a source of energy. The fact that RNA polymerase only gets access to the promoter ("the chair") in the presence of lactose means the cell will only produce proteins required for lactose breakdown when there is actually lactose to break down. Otherwise, the repressor binds to the operator, and neither permease nor B-galactosidase is made.

In addition to negative regulation by the repressor, the lac operon is positively regulated by cAMP, cyclic adenosine monophosphate. E. coli doesn't really like lactose. Positive regulation by cAMP ensures the cell will use lactose as a carbon source only in the absence of glucose, which is the preferred sugar for most cells because it is more efficient metabolically. This is known as catabolite repression. Glucose and cAMP levels are inversely proportional; the higher the concentration of glucose, the lower the concentration of cAMP. Only under low concentrations of glucose and high concentration of cAMP will the lac operon be activated and galactosidase and permease be produced. 

So there you have it. The operon is on only in the presence of lactose, when lactose binds and inactivates the repressor. The operon is on (to a much higher degree) when the cell is "starving" because there's no glucose around, and so the cell uses lactose as a backup carbon source.