Metabolism - Lec 4 Flashcards Preview

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Flashcards in Metabolism - Lec 4 Deck (18)
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1
Q

what is allostery?

A

activation or inhibition of an enzyme by binding at the regulatory site

it affects catalytic activity

2
Q

an example is covalent modification such as de/phosphorylation.

what is this ?

A

de/phosphorylation
introducing the bulky negative PO4 2-
this can alter protein strucutre and hence activity

3
Q

what are the principles of metabolic pathway regulation?

A

Irreversible steps are possible points of regulation

reducing activity - reduces flux of substrates through pathway - reduces products

reversible steps are not regulated, reactions will always come to equilibrium - product levels are unaffected

4
Q

how does product inhibition work ?

A

if pathway intermediates build up, they will sit at equilibrium and flux through pathway slows - this is inefficient

overall result is a reduced rate of catalysis

most common biological solution to this is to inhibit the first step of the pathway, reduces substrate entry and intermediate build up. this is called FEEDBACK INHIBITION
the trigger for this is high concentrations of product

5
Q

what is the committing step?

A

it is a step, that can be inhibited, that would commit the substrate to this path.

if inhibited we can divert substrate into other pathways

6
Q

how is the catabolic pathway regulated?

A

it is inhibited by high energy signals - ATP NADH FADH2 - Body says lots of energy atm, stop making more - divert to storage

its activated by low energy signals - ADP, NAD+,FAD -
body says low energy need to make more - bring stuff out of storage

7
Q

Outline hormone regulation

A

hormones bind to a receptor to activate a signalling pathway

Protein kinases will phosphorylate or protein phospahte will dephosphorylate the target enzyme

altering activity

8
Q

what is feed forward?

A

early pathway substrate provides positive allosteric signal

activates a enzyme later in the pathway

an example of this is fructose 2,6 Bisphosphate

9
Q

give two examples of phosphoregulation

A
  1. Adrenaline - activates protein kinase A
    Phosphorylation activates Phosphorylase kinase
    Phosphorylation of Glycogen Phosphorylase - stimulates glycogen breakdown
    a multi step respone
  2. Insulin - stimulated signalling pathway actiavtes protein phosphotase 1
    desphosphorylates and activates pyruvate dehydrogenase - stimulating glucose ultilisaiton
    dephosphorylates glycogen phosphotase - inhibiting glycogen breakdown

Key Point : phosphorylation and dephosphroylation may be stimulatory or inhbitory depending on the target enzyme

10
Q

What is the key regulator of glycolysis ?

A

phosphofructokinase 1

11
Q

how does phosphofructokinase 1 (PFK) work ?

A

converts Fructose 6 phosphate to fructose 1,6- bisphosphate - this provides a energtically unstable molecule to break into two c3 molecules

uses an ATP to ADP - energy used

12
Q

how is PFK regulated ?

A

Allosteric regulation (Muscle) -

  • Inhibited by high ATP
  • Stimulated by high AMP

Hormonal regulation (Liver) -

  • Stimulated by Insulin
  • Inhibited by Glucagon

Fructose 2,6 bisphosphate production from Fructose 6 phosphate also stimulates PFK 1
it is fructose FEED FORWARD encouraging fructose metabolsim

there are other inhibitors such as H+ ions, Citrate from TCA cycle and PEP (extra)

13
Q

What are other regulation mechanisms in glycolysis ?

may be best to draw the pathway in full if you can

A

Hexokinase - 1st step phosphorylation uses ATP
inhibted by Glucose 6 phosphate - G-6-P - a intermediary later in pathway

High NADH, Low NAD+

Hormonal Activation - PFK and Pyruvate kinase
high amounts of insulin to glucagon ratio will lead to this activation of pathway

14
Q

consider and explain product inhibition by NADH

A

High NADH or low NAD+ is a high energy signal
causes a product inhibtion of step 6
inhibiting glycolyisis
substrates feed out into storage pathways

15
Q

How is PKF phosphoregulated ?

pyruvate kinase is the same

A

insulin signals to Protein phosophotase 1 which removes P and stimulates PKF-1

Glucagon signals to protein kinase A (PKA) - adds P - inhibits PKF-1

16
Q

what does pyruvate kinase do, how is it phosphoregulated?

A

final step to produce ATP and Pyruvate

exactly the same system as PKF phosphoregulation

insulin signals to Protein phosophotase 1 which removes P and stimulates pyruvate kinase

Glucagon signals to protein kinase A (PKA) - adds P - inhibits Pyruvate kinase

17
Q

how is hexokinase regulated ?

A

hexokinase is the first step to phophorylate, using an ATP

inhibition at step 6 - High NADH, Low NAD+
inhibiton at step 4 - PKF inhibted due to high energy siganls

prevents metabolism of fructose1,6 Bisphosphate backing up th eintermediates
Glucose-6-phosphate Builds up- G-6-P is a negative regulator of hexokinase

summary - the inhibition of molecules later in the path from high energy signals leads to build up of G-6-P which ihibts hexokinase

18
Q

what is the committing step of glycolysis ?

A

Phosphofuctokinase 1 - stopping this allows feed out into other pathways