1. Regulatory Strategies

Question 1

Why must all cells regulate their metabolism?

Answer 1

To meet basic requirements (energy, carbon, nitrogen, minerals) and to respond to changing external conditions (carbon, solutes, pH)

Question 2

What is the concentration of the solute compare to enzymes in the intracellular environment?

Answer 2

Equal

Question 3

What two types of substrate are there? Where may they be present?

Answer 3

Hydrophilic substrate - may only cross membranes via transporter proteins

Hydrophobic substrates - associate with membranes/binding proteins/lipid droplets

Question 4

Which coenzymes are conserved?

Answer 4

NADH, NADPH, ATP, GTP, FADH2

Question 5

What is the equation for the energy charge of a cell? Give a rough estimate of an average cell energy charge.

Answer 5

[ATP]+0.5[ADP]/[ATP]+[ADP]+[AMP]

0.9-0.95

EC may go from 0-1

Question 6

Why is it important for the ratios of the forms of conserved metabolites to be maintained within trick limits?

Answer 6

The changing ratio will affect the direction of reactions. To avoid this, any deviation from ideal ratios stimulates the cell to implement measures to equalise.

Question 7

What methods may cells use to regulate their internal processes (4)? Keeping the conserved metabolite ratio the same.

Answer 7

1. Take up different substrates (altering transport proteins)
2. Halt uptake of other substrates
3. Process different substrates (alter metabolic pathways)
4. Synthesise new substances (that aren’t available in surrounding)

Question 8

In multicellular organisms the external environment (of the cells) is usually kept constant, so why may cells deliberately alter substrate availability? Give an example

Answer 8

In order to support changes in metabolism of other cells, or to spare substrates for other tissues

e.g. Some tissues internalise glucose transporters in the fasting state, and adipose increases fatty acid release

Question 9

What 7 ways may proteins be regulated?

Answer 9

1. Transcription
2. mRNA stability
3. Translation
4. Degradation
5. Location
6. Allosteric Control
7. Covalent modification

Question 10

How does protein regulation through transcription occur?

Answer 10

Control of which genes are transcribed - vary in different conditions

Question 11

How does protein regulation occur through mRNA stability?

Answer 11

The rate at which mRNA is degraded is regulated - so longer lasting mRNAs can transcribe more proteins (and vice versa)

Question 12

How does protein regulation occur through degradation?

Answer 12

Proteins may be tagged by ubiquitin and degraded by 26S proteasomes

OR

Broken down in lysosomes

Question 13

How will halting the degradation of a protein with a short half life vary its concentration compared to halting the degradation of a long half lie protein?

Answer 13

Short half life will quickly increase concentration whereas the long half life will increase concentration but much slower

Question 14

How does the location of the protein affect its efficacy? Roughly how long does it take to for a protein to be moved?

Answer 14

Protein must be in the right location to work. This takes seconds-minutes (quick)

Question 15

What is allosteric control? How fast does this control protein levels?

Answer 15

Allosteric control is the reversible, non-covalent binding of effectors to enzymes resulting in activation or inhibition.

milliseconds-seconds

Question 16

What is the difference between the T state and the R state?

Answer 16

T (tense) star does not allow the substrate to bind well, whereas the R (relaxed) state binds substrate easily

Question 17

In allosteric control, what is the relationship between v0 and [S] if the substrate binds and stabilises the R-state of the oligomeric protein? What does this mean for the sensitivity of the enzyme/protein?

Answer 17

There is a sigmoidal relationship between v0 and [S].

The steep gradient of the sigmoidal curve (at some points) means there is a large variation in v0 for small variation in [S], meaning that the protein is very sensitive to changes in [S]

Question 18

What is the difference between competitive, non-competitive and uncompetitive inhibitors? How may these affect the Km and Vmax of the enzyme they are bound to?

Answer 18

Competitive: Binds to the active site, increases Km, Vmax constant

Non-competitive: Binds away from active site of E and E:S complexes, decreases Vmax, Km remains the same

Uncompetitive: Binds E:S complex away from active site, Vmax decreases, Km decreases

Question 19

What two types of effector are there?

Answer 19

Homotropic (if effector is enzymes substrate/product) and heterotropic

Question 20

How does covalent modification of proteins occur? What modifications may be made? How fast does this occur?

Answer 20

Enzyme catalysed (stable)

Phosphorylation, Adenylation, ADP-Ribosylation, methylation

Seconds-minutes

Question 21

Which amino acids may be phosphorylated?

Answer 21

Serine, Threonine and Tyrosine (on the hydroxyl groups)

Question 22

Which enzymes is phosphorylation catalysed by? Which enzyme catalyse dephosphorylation?

Answer 22

(Protein) Kinases phosphorylate

(Phosphoprotein) phosphatase dephosphorylates

Question 23

What does phosphorylation do to proteins?

Answer 23

Activate or inhibit them

Question 24

What kind of reactions do rate-limiting enzymes catalyse? Where are regulatory enzymes typically placed on an enzyme pathway? Why?

Answer 24

These enzymes catalyse reactions where cellular concentrations are far from equilibrium. Reactions are usually exothermic and irreversible.

Just after branch points, ensuring that the pathway is ‘committed’

Question 25

What is the flux control coefficient? What is it’s symbol? How may it be calculated?

Answer 25

Defines which enzymes contribute the most towards pathway control

C

Experimentally determined (may change depending on circs.)

Question 26

What do the C values for a pathway always add up to?

Answer 26

1