Lecture 16 - Regulation Flashcards
What is an example of short term regulation?
Feedback inhibition (and activation)
What is an example of post-translational control?
Protein kinase and protein phosphatase in glycogen metabolism control by covalent modification (+/- phosphate)
What is an example of long term control?
Control of RNA and protein levels because the response time is longer
What is an example of compartmentation regulation?
Beta-oxidation occurs inside the mitochondria, whereas fatty acid synthesis occurs in the cytoplasm
What is an example of hormonal regulation?
Glycogen regulation
How are branched pathways regulated?
1) Multiple enzyme control
2) Sequential control
3) Synergistic feedback
Describe multiple enzyme control
Multiple alleles of the same enzyme (1 and 2) catalyze a step early in the pathway, and are affected differently by different inhibitors (E and G)
What is the problem with multiple enzyme control?
Additional sites of control are required in each branch after the initial branch point
Describe sequential control
The end products inhibit a step after the branch, which causes a build-up of an intermediate, which in turn acts sequentially to inhibit a step earlier in the pathway
Describe synergistic feedback
- 2 end products work synergistically to inhibit a step early in the pathway and together have a much larger effect than individually
- Can be cumulative (effects of E and G are additive) or concerted (neither has an effect individually)
What does control of transcription affect?
The number of mRNA molecules produced, thereby affecting the number of protein (enzyme) molecules produced
Is transcriptional control common? Why or why not?
Yes because it provides greater energy efficiency in stopping both RNA and protein synthesis
What is an operon?
A grouping of genes, the products of which have a common metabolic purpose
What is the function of lac operon?
Metabolism of lactose (galactose-beta1,4-glucose)
What does lac operon encode?
- Transport protein (lactose permease) to transport lactose into the cell
- Cleavage enzyme (beta-galactosidase) to cleave the 2 sugars
- Beta-galactoside transacetylase for detoxification
Which reactions does beta-galactosidase catalyze?
1) Lactose galactose + glucose
2) Galactose + glucose allolactose
What affects the synthesis of beta-galactosidase mRNA?
The carbon sources present in the growth medium
When is beta-galactosidase produced?
When substrate is present
Is lac operon produced when succinate is present?
No
Is lac operon activated when lactose is present?
Yes, to digest the lactose
Is lac operon activated when glucose is added?
No, because glucose is a better substrate than lactose, so beta-galactosidase isn’t required
What are the 3 states of lac operon?
1) Repressed
2) Induced
3) Catabolite repressed
When is lac operon repressed?
When succinate is the carbon source
When is lac operon induced?
When lactose is present in the medium
When is lac operon catabolite repressed?
When glucose is in the medium
What does the I gene of lac operon do?
Encodes repressor protein
What does the Pi gene of lac operon do?
Promotes the I gene
What does the P gene of lac operon do?
Promotes the lac gene
What does the Z gene of lac operon do?
Encodes beta-galactosidase
What does the Y gene of lac operon do?
Encodes galactosidase permease
What does the A gene of lac operon do?
Encodes transacetylase
What does the O1 gene of lac operon do?
Main operator for the lac operon
Which genes of lac operon are the regulatory system?
I, O, and P
Which genes of lac operon are the structural genes?
Z, Y, and A
What does the crp gene encode? Is it linked to the lac operon?
- Encodes a transcription activator protein known as catabolite gene activator protein (CAP) or cAMP receptor protein (CRP)
- Not linked
What does CAP require for activity?
cAMP
What occurs in the repressed state of lac operon?
The repressor binds to the operator, which overlaps the promoter and prevents RNA polymerase and CAP from binding
What occurs in the induced state of lac operon?
- CAP-cAMP facilitates RNA-P binding to the promoter, which activates transcription
- Repressor is bound by allolactose
How does allolactose inhibit the repressor?
It brings the equilibrium of the repressor closer to the T (inactive) state
What occurs in the catabolite repressed state of lac operon?
- Glucose causes cAMP levels to drop, reducing the amount of CAP-cAMP
- Repressor is inactive because of the presence of lactose/allolactose
Is lac operon a catabolic or anabolic operon and why?
- Catabolic
- Only turned on when the substrate of the operon is present so energy is not wasted
Is trp operon a catabolic or anabolic operon and why?
- Anabolic
- Turned off when the product of the operon enzymes is present so that energy is not wasted
When is the trp operon induced?
When glucose is present as a substrate and no tryptophan is present
When is the trp operon repressed?
When tryptophan is added (no need to produce more)
How does the trp operon become repressed?
Tryptophan binds to the repressor protein, which binds to the operator, blocking the mRNA from the tryptophan synthetic enzymes
What are 2 examples of multiple feedback inhibition?
1) Threonine and methionine inhibit homoserine dehydrogenase
2) Threonine, homoserine, and isoleucine inhibiti aspartate kinases
What is an example of sequential feedback inhibition?
Isoleucine blocks threonine, which blocks homoserin
What is an example of synergistic feedback inhibition?
Isoleucine and lysine together inhibit aspartate semialdehyde
What are 2 examples of long term transcriptional control in the isoleucine synthesis pathway?
1) Threonine and isoleucine are corepressors of the operon with genes encoding aspartyl kinase 1 and homoserine dehydrogenase 2
2) Methionine is a corepressor of the operon with genes encoding aspartyl kinase 2 and homoserine dehydrogenase 1
