Lactose enter into cell with Help of permease....but permease enzyme is produced by lactose? Which one is first. Lac or permease?

Although when the repressor is bound (Or when CAP is unbound) transcription becomes incredibly difficult, it still occurs but just very, very inefficiently. So there will be tiny amounts of permease produced normally through these rare chance events, which can "kick start" the process if there happens to be lactose outside the cell :)

If the expression of the lac operon is induced by the isomer of lactose, allolactose, and beta-galactosidase, the protein product of this operon, is the enzyme responsible for lactose isomerisation, where does the initial allolactose come from? Is it a natural mechanism, as in, in happens spontaneously, or is some of the beta-galactosidase present in the cell anyway?

Very good question! To understand this it helps to keep in mind that very few things in biology are 100% — this sloppiness or leakiness turns out be absolutely critical for many biological processes. In the case of the _lac_ operon, there is a low level of expression even when it is shut-off by the _lac_ repressor. This means a small amount of the ß-galactosidase (encoded by _lacZ_ ) is always present. (The low level expression of the symporter encoded by _lacY_ (ß-galactoside permease) is also required to allow lactose into the cell.) There is a very extensive Wikipedia article on this: https://en.wikipedia.org/wiki/Lac_operon

Why is lac operon so important in modern molecular biology?

Great question. The reason I have found that the lac operon is so important, is that it is the most study operon and has become the most classic example of how an operon works. My biology teacher for AP said that is the most common example. Hope that helps!

if bacteria has both glucose lactose present and it chose to digest glucose first will it still transcribe lactose digestion proteins?

If it metabolized most if not all the glucose molecules, yes.

What three enzymes would be needed that will help process the lactose?

lactase is the main enzyme that breaks down lactose into glucose and galactose

what does the ack operon produce? is it lactose?

No, it produces lactase, which is an enzyme that breaks down lactose.

Is lac operon only related to lactose metabolism in E.coli? Does humans need any such operon to metabolise lactose??

Operons only occur in Prokaryotic genomes. E.coli is a prokaryote and is one of the most known and studied one, so it is easy to use it as an example.

Main content

The lac operon

Google Classroom

Regulation of genes for lactose utilization. lac repressor, catabolite activator protein, and cAMP.

Key points:

The lac operon of E. coli contains genes involved in lactose metabolism. It's expressed only when lactose is present and glucose is absent.
Two regulators turn the operon "on" and "off" in response to lactose and glucose levels: the lac repressor and catabolite activator protein (CAP).
The lac repressor acts as a lactose sensor. It normally blocks transcription of the operon, but stops acting as a repressor when lactose is present. The lac repressor senses lactose indirectly, through its isomer allolactose.
Catabolite activator protein (CAP) acts as a glucose sensor. It activates transcription of the operon, but only when glucose levels are low. CAP senses glucose indirectly, through the "hunger signal" molecule cAMP.

Introduction

Lactose: it's what's for dinner! While that may not sound delicious to us (lactose is the main sugar in milk, and you probably don't want to eat it plain), lactose can be an excellent meal for E. coli bacteria. However, they'll only gobble up lactose when other, better sugars – like glucose – are unavailable.

With that for context, what exactly is the lac operon? The lac operon is an operon, or group of genes with a single promoter (transcribed as a single mRNA). The genes in the operon encode proteins that allow the bacteria to use lactose as an energy source.

What makes the lac operon turn on?

E. coli bacteria can break down lactose, but it's not their favorite fuel. If glucose is around, they would much rather use that. Glucose requires fewer steps and less energy to break down than lactose. However, if lactose is the only sugar available, the E. coli will go right ahead and use it as an energy source.

To use lactose, the bacteria must express the lac operon genes, which encode key enzymes for lactose uptake and metabolism. To be as efficient as possible, E. coli should express the lac operon only when two conditions are met:

Lactose is available, and
Glucose is not available

How are levels of lactose and glucose detected, and how how do changes in levels affect lac operon transcription? Two regulatory proteins are involved:

One, the lac repressor, acts as a lactose sensor.
The other, catabolite activator protein (CAP), acts as a glucose sensor.

These proteins bind to the DNA of the lac operon and regulate its transcription based on lactose and glucose levels. Let's take a look at how this works.

Structure of the lac operon

The lac operon contains three genes: lacZ, lacY, and lacA. These genes are transcribed as a single mRNA, under control of one promoter.

Genes in the lac operon specify proteins that help the cell utilize lactose. lacZ encodes an enzyme that splits lactose into monosaccharides (single-unit sugars) that can be fed into glycolysis. Similarly, lacY encodes a membrane-embedded transporter that helps bring lactose into the cell.

The lacZ gene encodes an enzyme called β-galactosidase, which is responsible for splitting lactose (a disaccharide) into readily usable glucose and galactose (monosaccharides).

The lacY gene encodes a membrane protein called lactose permease, which is a transmembrane "pump" that allows the cell to import lactose.

The lacA gene encodes an enzyme known as a transacetylase that attaches a particular chemical group to target molecules. It's not clear if this enzyme actually plays any role in lactose breakdown. (Weird but true!)

In addition to the three genes, the lac operon also contains a number of regulatory DNA sequences. These are regions of DNA to which particular regulatory proteins can bind, controlling transcription of the operon.

_Image modified from "Prokaryotic gene regulation: Figure 3," by OpenStax College, Biology (CC BY 4.0)._

The promoter is the binding site for RNA polymerase, the enzyme that performs transcription.
The operator is a negative regulatory site bound by the lac repressor protein. The operator overlaps with the promoter, and when the lac repressor is bound, RNA polymerase cannot bind to the promoter and start transcription.
The CAP binding site is a positive regulatory site that is bound by catabolite activator protein (CAP). When CAP is bound to this site, it promotes transcription by helping RNA polymerase bind to the promoter.

Let's take a closer look at the lac repressor and CAP and their roles in regulation of the lac operon.

The lac repressor

The lac repressor is a protein that represses (inhibits) transcription of the lac operon. It does this by binding to the operator, which partially overlaps with the promoter. When bound, the lac repressor gets in RNA polymerase's way and keeps it from transcribing the operon.

When lactose is not available, the lac repressor binds tightly to the operator, preventing transcription by RNA polymerase. However, when lactose is present, the lac repressor loses its ability to bind DNA. It floats off the operator, clearing the way for RNA polymerase to transcribe the operon.

This change in the lac repressor is caused by the small molecule allolactose, an isomer (rearranged version) of lactose. When lactose is available, some molecules will be converted to allolactose inside the cell. Allolactose binds to the lac repressor and makes it change shape so it can no longer bind DNA.

Allolactose is an example of an inducer, a small molecule that triggers expression of a gene or operon. The lac operon is considered an inducible operon because it is usually turned off (repressed), but can be turned on in the presence of the inducer allolactose.

Catabolite activator protein (CAP)

When lactose is present, the lac repressor loses its DNA-binding ability. This clears the way for RNA polymerase to bind to the promoter and transcribe the lac operon. That sounds like the end of the story, right?

Well...not quite. As it turns out, RNA polymerase alone does not bind very well to the lac operon promoter. It might make a few transcripts, but it won't do much more unless it gets extra help from catabolite activator protein (CAP). CAP binds to a region of DNA just before the lac operon promoter and helps RNA polymerase attach to the promoter, driving high levels of transcription.

CAP isn't always active (able to bind DNA). Instead, it's regulated by a small molecule called cyclic AMP (cAMP). cAMP is a "hunger signal" made by E. coli when glucose levels are low. cAMP binds to CAP, changing its shape and making it able to bind DNA and promote transcription. Without cAMP, CAP cannot bind DNA and is inactive.

CAP is only active when glucose levels are low (cAMP levels are high). Thus, the lac operon can only be transcribed at high levels when glucose is absent. This strategy ensures that bacteria only turn on the lac operon and start using lactose after they have used up all of the preferred energy source (glucose).

So, when does the lac operon really turn on?

The lac operon will be expressed at high levels if two conditions are met:

Glucose must be unavailable: When glucose is unavailable, cAMP binds to CAP, making CAP able to bind DNA. Bound CAP helps RNA polymerase attach to the lac operon promoter.
Lactose must be available: If lactose is available, the lac repressor will be released from the operator (by binding of allolactose). This allows RNA polymerase to move forward on the DNA and transcribe the operon.

These two events in combination – the binding of the activator and the release of the repressor – allow RNA polymerase to bind strongly to the promoter and give it a clear path for transcription. They lead to strong transcription of the lac operon and production of enzymes needed for lactose utilization.

Putting it all together

Now that we’ve seen all the moving parts of the lac operon, let’s put what we’ve learned together to see how the operon reacts to a variety of different conditions (presence or absence of glucose and lactose).

Glucose present, lactose absent: No transcription of the lac operon occurs. That's because the lac repressor remains bound to the operator and prevents transcription by RNA polymerase. Also, cAMP levels are low because glucose levels are high, so CAP is inactive and cannot bind DNA.
Glucose present, lactose absent: No transcription of the lac operon occurs. That's because the lac repressor remains bound to the operator and prevents transcription by RNA polymerase. Also, cAMP levels are low because glucose levels are high, so CAP is inactive and cannot bind DNA.
_Image modified from "Prokaryotic gene regulation: Figure 3," by OpenStax College, Biology (CC BY 4.0)._
Glucose present, lactose present: Low-level transcription of the lac operon occurs. The lac repressor is released from the operator because the inducer (allolactose) is present. cAMP levels, however, are low because glucose is present. Thus, CAP remains inactive and cannot bind to DNA, so transcription only occurs at a low, leaky level.
Glucose present, lactose present: Low-level transcription of the lac operon occurs. The lac repressor is released from the operator because the inducer (allolactose) is present. cAMP levels, however, are low because glucose is present. Thus, CAP remains inactive and cannot bind to DNA, so transcription only occurs at a low, leaky level.
_Image modified from "Prokaryotic gene regulation: Figure 3," by OpenStax College, Biology (CC BY 4.0)._
Glucose absent, lactose absent: No transcription of the lac operon occurs. cAMP levels are high because glucose levels are low, so CAP is active and will be bound to the DNA. However, the lac repressor will also be bound to the operator (due to the absence of allolactose), acting as a roadblock to RNA polymerase and preventing transcription.
Glucose absent, lactose absent: No transcription of the lac operon occurs. cAMP levels are high because glucose levels are low, so CAP is active and will be bound to the DNA. However, the lac repressor will also be bound to the operator (due to the absence of allolactose), acting as a roadblock to RNA polymerase and preventing transcription.
_Image modified from "Prokaryotic gene regulation: Figure 3," by OpenStax College, Biology (CC BY 4.0)._
Glucose absent, lactose present: Strong transcription of the lac operon occurs. The lac repressor is released from the operator because the inducer (allolactose) is present. cAMP levels are high because glucose is absent, so CAP is active and bound to the DNA. CAP helps RNA polymerase bind to the promoter, permitting high levels of transcription.
Glucose absent, lactose present: Strong transcription of the lac operon occurs. The lac repressor is released from the operator because the inducer (allolactose) is present. cAMP levels are high because glucose is absent, so CAP is active and bound to the DNA. CAP helps RNA polymerase bind to the promoter, permitting high levels of transcription.
_Image modified from "Prokaryotic gene regulation: Figure 3," by OpenStax College, Biology (CC BY 4.0)._

Summary of lac operon responses

Glucose	Lactose	CAP binds	Repressor binds	Level of transcription
+	-	-	+	No transcription
+	+	-	-	Low-level transcription
-	-	+	+	No transcription
-	+	+	-	Strong transcription

Explore outside of Khan Academy

Do you want to learn more about the lac operon? Check out this scrollable interactive from LabXchange.

LabXchange is a free online science education platform created at Harvard’s Faculty of Arts and Sciences and supported by the Amgen Foundation.

This article is licensed under a CC BY-NC-SA 4.0 license.

References:

Berg, J. M., Tymoczko, J. L., and Stryer, L. (2002). Prokaryotic DNA-binding proteins bind specifically to regulatory sites in operons. In Biochemistry (5th ed., section 31.1). New York, NY: W. H. Freeman. Retrieved http://www.ncbi.nlm.nih.gov/books/NBK22512/.

Bergmann, D. C. (2011). Gene regulation: How to only make RNA (and protein) at the right time and place. In BIO41: 2011 Molecular biology lectures on DNA, RNA and biotechnology (pp. 9-13).

Inducer. (2015, August 11). Retrieved Saturday, April 16 from Wikipedia: https://en.wikipedia.org/wiki/Inducer.

Kovach, T. K. (2014, February 26). Jacob-Monod: The lac operon. In Gene control. Retrieved from https://www.khanacademy.org/test-prep/mcat/biomolecules/gene-control/v/jacob-monod-the-lac-operon.

OpenStax College, Biology. (2015, September 29). Prokaryotic gene regulation. In OpenStax CNX. Retrieved from http://cnx.org/contents/GFy_h8cu@9.87:drSgdNIj@5/Prokaryotic-Gene-Regulation.

Reece, J. B., Urry, L. A., Cain, M. L., Wasserman, S. A., Minorsky, P. V., and Jackson, R. B. (2011). Bacteria often respond to environmental change by regulating transcription. In Campbell biology (10th ed., pp. 361-365). San Francisco, CA: Pearson.

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Posted 7 years ago. Direct link to 😊's post “Lactose enter into cell w...”
Lactose enter into cell with Help of permease....but permease enzyme is produced by lactose? Which one is first. Lac or permease?
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(9 votes)
Answer
- alannah.king13
  Posted 6 years ago. Direct link to alannah.king13's post “Although when the repress...”
  Although when the repressor is bound (Or when CAP is unbound) transcription becomes incredibly difficult, it still occurs but just very, very inefficiently. So there will be tiny amounts of permease produced normally through these rare chance events, which can "kick start" the process if there happens to be lactose outside the cell :)
  Button navigates to signup page
  (18 votes)
Revan Rangotis
Posted 6 years ago. Direct link to Revan Rangotis's post “If the expression of the ...”
If the expression of the lac operon is induced by the isomer of lactose, allolactose, and beta-galactosidase, the protein product of this operon, is the enzyme responsible for lactose isomerisation, where does the initial allolactose come from?

Is it a natural mechanism, as in, in happens spontaneously, or is some of the beta-galactosidase present in the cell anyway?
Button navigates to signup pageButton navigates to signup page
(5 votes)
Answer
- tyersome
  Posted 6 years ago. Direct link to tyersome's post “Very good question! To u...”
  Very good question!
  
  To understand this it helps to keep in mind that very few things in biology are 100% — this sloppiness or leakiness turns out be absolutely critical for many biological processes.
  
  In the case of the lac operon, there is a low level of expression even when it is shut-off by the lac repressor. This means a small amount of the ß-galactosidase (encoded by lacZ ) is always present.
  (The low level expression of the symporter encoded by lacY (ß-galactoside permease) is also required to allow lactose into the cell.)
  
  There is a very extensive Wikipedia article on this:
  https://en.wikipedia.org/wiki/Lac_operon
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  (5 votes)
http://facebookid.khanacademy.org/1476580007
Posted 7 years ago. Direct link to http://facebookid.khanacademy.org/1476580007's post “Why is lac operon so impo...”
Why is lac operon so important in modern molecular biology?
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(2 votes)
Answer
- amconnel99
  Posted 7 years ago. Direct link to amconnel99's post “Great question. The reaso...”
  Great question. The reason I have found that the lac operon is so important, is that it is the most study operon and has become the most classic example of how an operon works. My biology teacher for AP said that is the most common example. Hope that helps!
  Button navigates to signup page
  (5 votes)
isabellewild01
Posted 3 years ago. Direct link to isabellewild01's post “what happens if the repre...”
what happens if the repressor is is mutated and cannot bind to the operator. How would this affect transcription when both glucose and lactose are present
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Christina Lynn
Posted 7 years ago. Direct link to Christina Lynn's post “how are E. coli able to u...”
how are E. coli able to use up all of the glucose present before turning to lactose?
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Bailan
Posted 6 years ago. Direct link to Bailan's post “Is lac operon only relate...”
Is lac operon only related to lactose metabolism in E.coli?
Does humans need any such operon to metabolise lactose??
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(1 vote)
Answer
- Carl Daoud
  Posted 6 years ago. Direct link to Carl Daoud's post “Operons only occur in Pro...”
  Operons only occur in Prokaryotic genomes. E.coli is a prokaryote and is one of the most known and studied one, so it is easy to use it as an example.
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Jana
Posted a year ago. Direct link to Jana's post “if bacteria has both gluc...”
if bacteria has both glucose lactose present and it chose to digest glucose first will it still transcribe lactose digestion proteins?
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- Goro Majima
  Posted a year ago. Direct link to Goro Majima's post “If it metabolized most if...”
  If it metabolized most if not all the glucose molecules, yes.
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annika.ermold
Posted 2 years ago. Direct link to annika.ermold's post “What three enzymes would ...”
What three enzymes would be needed that will help process the lactose?
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- David
  Posted 2 years ago. Direct link to David's post “lactase is the main enzym...”
  lactase is the main enzyme that breaks down lactose into glucose and galactose
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Dianna Lozano
Posted a year ago. Direct link to Dianna Lozano's post “what does the ack operon ...”
what does the ack operon produce? is it lactose?
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- RiverclanWarrior
  Posted a year ago. Direct link to RiverclanWarrior's post “No, it produces lactase, ...”
  No, it produces lactase, which is an enzyme that breaks down lactose.
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nur emira ahmad samsuri
Posted 3 years ago. Direct link to nur emira ahmad samsuri's post “What happen when a strain...”
What happen when a strain with a mutation in which the Shine-Dalgarno sequence has been deleted from the gene encoding adenyl cyclase. The mutant is grown in a medium containing lactose and glucose.
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AP®︎/College Biology

Course: AP®︎/College Biology > Unit 6