L8- Regulation of metabolic pathways Flashcards

1
Q

where does glycolysis occur

A

in the cytoplasm of all tissues

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2
Q

how can glycolysis operate anaerobically

A

LDH

  • production of NADH (reducing powers) meaning glycolysis can continue
  • e.g. in RBC, muscles etc
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3
Q

allosteric means

A

other site

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4
Q

enzyme shave two sites

A

catalytic site

regulatory site

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5
Q

catalytic site

A

substrate binding

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6
Q

regulatory site

A

binding of specific regulatory molecules

  • affects catalytic activity
  • can activate or inhibit
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7
Q

allosteric regulation cause

A

covalent modification e.g. phosphorylation/ dephosphorylation

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8
Q

covalent modification e.g. phosphorylation/ dephosphorylation

A

alters protein conformation and therefore activity

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9
Q

pathways are regulated by

A

irreversible steps

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10
Q

with irreversible steps reduced activity reduces the rate of flow of..

A

substrates through the pathway directly, reducing levels of product

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11
Q

with reversible steps, even when inhibited

A

reactions still come to equilibrium so levels of product unaffected

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12
Q

product inhibition

A

where the product displaces the equilibrium towards the substrate
- reduces rate of catalysis of substrate to product

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13
Q

feedback inhibitor

A

where final product inhibits first enzyme in pathway

- reduces entry of substrate into the pathway leading to build up of intermediates

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14
Q

committing step

A

inhibition of committing step allows substrate to be diverted into other pathways

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15
Q

regulation of enzymes can be

A

inhibitory or stimulatory

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16
Q

catabolic pathways such as glycolysis and the kerb cycle are inhibited

A

by high energy signals such as ATP, NADH and FAD2H

17
Q

catabolic pathways such as glycolysis and the kerb cycle are stimulated by

A

low energy signals such as o ADP, AMP, NAD+, FAD+

18
Q

hormonal regulation

A

hormone receptor binding can activate signalling pathways e.g. insulin (tyrosine kinase receptor)
- this can activate Protein kinases (phosphorylation) or phosphates (dephosophorylation)

19
Q

phosphorylation/ dephospho rylation of target enzyme

A

alters protein conformation/ activity positively or negatively depending on the target enzyme

20
Q

example of phosphorylation: adrenaline

A

adrenaline binds to GPCR
o Activates protein kinase A
o Phosphorylation activates phosphorylase kinase
o Phosphorylation of glycogen phosphorylase
i. Stimulates glycogen break down

21
Q

example of phosphorylation: insulin

A

Insulin binds to TK receptor
o Stimulated signalling pathway activates protein phosphatase 1
o Dephosphorylates/activates pyruvate dehydrogenase
i. Stimulates glucose utilisation
o Dephosphorylates glycogen phosphorylase
i. Inhibits glycogen breakdown

22
Q

feed forward

A
  • Early pathway substrate provides positive allosteric signal to stimulate a later enzyme to activate the pathway
23
Q

name the 3 key regulators of glycolysis

A
  1. Hexokinase (glucokinase in the liver) (1)
  2. Phosphofructokinase-1 (3)
  3. Pyruvate kinase (10)
24
Q

hexokinase

A

Product inhibition by Glucose-6-P

 Enzyme activity will reduce as more glucose is catalysed to glucose-6-p- negative regulator

25
Q

phosphofructokinase-1 (PFK) is the most

A

important enzyme in the regulation of glycolysis

26
Q

how can PFK regulate glycolysis

A

allosteric regulation (muscle)

hormonal regulation (liver)

27
Q

PFK and allosteric regulation (muscle)

A

o Inhibited by high ATP

o Stimulated by high AMP

28
Q

PFK and hormonal regulation (liver)

A

o Stimulated by insulin

o Inhibited by glucagon

29
Q

Pyruvate kinase

A

regulated via phosphoregulaton

  • final stage of glycolysis
30
Q

when glucagon (starvation hormone) binds to its receptor

A

protein kinase A conc in the cell increases and this phosphorylated ADP–> ATP ( low energy signal)
-INHIBITING GLYCOLYSIS

31
Q

when insulin (well fed hormone) binds to it receptor

A

protein phosphatase 1 conc increases and this dephosphorylates ATP–> ADP (high energy signal)
- STIMUALTING GLYCOLYSIS

32
Q

hexokinase is inhibited by

A

glucose-6-phosphate (its own product) - therefore PRODUCT INHIBITION

33
Q

high ATP ……. PFK

A

inhibits

34
Q

high AMP ……. PFK

A

stimulates

35
Q

where is the commuting step in glycolysis

A

phosphofructokinase

36
Q

high insulin and low glucagon will

A

stimulate glycolysis by causing enzyme depths (more high energy signals such as ADP)