9 - Regulation Of Metabolic Pathways Flashcards

1
Q

What is allostery?

A

Where a regulator (activator or inhibitor) binds at ‘another’ site. Changes activity of enzyme

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2
Q

What is covalent modification of an enzyme?

A

Enzyme gets de/phosphorylated, changing the conformity of the protein and therefore the activity

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3
Q

What are the two ways of product inhibition in metabolic pathway?

A

1. Increase in conc of an intermediate in a reversible reaction leads to a shift in equilibrium. Binding rate of previous intermediate decreases so increase in pathway intermediates

2. Feedback inhibition - allosteric binding of end product to first enzyme in pathway. Reduces entry of substrate and therefore stops build up of intermediates

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4
Q

What is the commiting step in a pathway?

A

Irreversible enzymatic reaction that once occurs, the molecules are comitted and will end up in the end product of the pathway

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5
Q

What is the committed step of glycolysis?

A

Point where phosphofructokinase-1 phosphorylates fructose-6-p

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6
Q

What reactions of glycolysis are regulated and why?

A

1, 3 and 10. They are irreversible. Reversible cannot be regulated as equilibrium will still be reached

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7
Q

How can regulating the committing step affect a pathway?

A

Inhibiting the commiting step diverts substrate to other pathways. e.g product of pathway could allosterically inhibit enzyme for substrate

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8
Q

How are catabolic pathway enzymes regulated?

A
  • High energy signals : ATP, NADH, FADH2 inhibit
  • Low energy signals: AMP, ADP, NAD activate
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9
Q

How can hormonal regulation affect metabolic pathways?

A
  • Hormone binds to receptor
  • This activates signalling pathway and therefore activates protein kinase or protein phosphotase
  • These enzymes de/phosphorylate target enzymes involved in glycolysis and change their conformity so either activate or deactivate them
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10
Q

What type of regulation is feed forward an example of?

A
  • Allosteric
  • Substrate provides positive allosteric signal to enzymes further down the pathway
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11
Q

Give two examples of phosphoregulation with hormones.

A

Adrenaline

Activates protein kinase A.

Phosphorylation activates phosphorylase kinase and glycogen phosphorylase. Stimulate glycogen breakdown

Insulin

Activate protein phosphotase 1.

  • Dephosphorylates pyruvate dehydrogenase, activating it and stimulating glucose utilisation.
  • Dephosphorylates glycogen phosphorylase which inhibits it, inhibiting glycogen breakdown
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12
Q

What is the key regulator of glycolysis?

A

Phosphofructokinase-1

(first commiting step)

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13
Q

What does phosphofructokinase do?

A

Catalyse phosphorylation of fructose-6-p to fructose-1,6-p

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14
Q

How is glycolysis metabolicaly inhibited?

A

High energy levels of NADH from step 5 causes inhibition of step 6 (phosphorylation)

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15
Q

How is glycolysis allostericaly regulated?

A

Phosphofructokinase 1

Activated: AMP, F2,6-BP (high fructose levels)

Inhibited: ATP, PEP (last product of glycolysis), Citrate (Krebs), H+ (metabolism forms acid)

Hexokinase

Inhibited: G-6-P which builds up due to stop of step 4 and 6

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16
Q

How is glycolysis regulated by hormones? (Phosphoregulation)

A

PFK1

Insulin –>Protein Phosphatase–> Dephosphorylate PFK–> +

Glucagon –> Protein Kinase A –> Phosphorylate PFK –> -

Pyruvate Kinase** **(Final enzyme)

Same as above

17
Q

Explain all of the ways glycolysis is regulated.

A
18
Q

How is step 1 of glycolysis regulated?

A

Hexokinase has product inhibition by G-6-P