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Metabolism > Glycolysis > Flashcards

Glycolysis Flashcards

1
Q

Where is glucose a primary fuel?

A

brain, red blood cells and the renal medulla

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2
Q

Is glycolysis aerobic or anaerobic?

A

anaerobic

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3
Q

Glycolysis definition

A

Metabolic pathway that converts glucose into pyruvate and a hydrogen ion. Occurs in a hypoxic environment

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4
Q

Where does it take place?

A

cytoplasm

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5
Q

brief 3 stages

A

energy investment, 6C splitting and energy harvest

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6
Q

What mediates the control?

A

supply and demand, supply in terms of selecting the best fuel, demand in terms of the energy needs of the cell

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7
Q

What does glycolysis produce as a waste product?

A

lactate

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8
Q

How is glucose taken up into the cell?

A

GLUT1-4 mediated facilitated diffusion and SGLT1-2 mediated secondary active transport

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9
Q

Differences in tissue uptake + main transporter

A

Liver, endocrine pancreas, dependent on plasma glucose concentration- GLUT2- insulin independent

peripheral tissues- depends on energy needs of tissues and is regulated in tissues that can use non-carbohydrate substrates- GLUT 4- insulin dependent

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10
Q

When is uptake independent of substrate concentration?

A

Km is less than physiological

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11
Q

When is uptake highly dependent on substrate concentration?

A

Km is more than or equal to physiological

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12
Q

The three stages of glycolysis?

A

glucose priming, splitting of P’ated i/mediate, oxidoreduction phosphorylation

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13
Q

First reaction in glycolysis + enzyme

A

glucose phosphorylation

ATP–> ADP , glucose –> glucose 6-phosphate

hexokinase/glucokinase

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14
Q

Differences between hexokinase and glucokinase

A 
hexokinase
- most tissues
regulatory step
broad substrate specificity 
low kM (high affinity)
low vMax

glucokinase

  • liver, pancreatic islets
  • similar specificity
  • different regulation
  • high km
  • high vmax
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15
Q

second reaction in glycolysis + enzyme

A

reversible isomerisation reaction

glucose 6-phosphate into fructose 6-phosphate

enzyme= phosphoglucose isomerase

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16
Q

Third reaction in glycolysis + enzyme

A

fructose 6-phosphate into fructose 1,6- bisphosphate

ATP—> ADP

phosphofructokinase-1

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17
Q

fourth reaction + enzyme

A

fructose-1,6-bisphosphate –> glyceraldehyde 3-phosphate + dihydroxyacetone phosphate

aldolase

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18
Q

Why does the proportion of glyceraldhyde 3-phosphate and dihydroxyacetone phosphate vary?

A

They can be changed from one form to the other using triose phosphate isomerase

at equilibrium, 96% of triose phosphate is DHAP

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19
Q

What if formed in the fifth reaction?

A

1,3-biphosphoglycerate

20
Q

How does the oxidation of glyceraldehyde-3-phosphate take place?

A

reduction of cofactor NAD+ and Pi to form NADH and an H+

same time OAA becomes malate, thanks to NADH

21
Q

Where is the original energy of glucose?

A

1,3-bisPGA used directly for the synthesis of ATP

NADH used indirectly for the synthesis of ATP

22
Q

6th step + enzyme

A

1,3- bisphosphoglycerate to 3-phosphoglycerate

ADP to ATP

phosphoglycerate kinase

23
Q

What type of reaction is the 6th step?

A

substrate level phosphorylation

24
Q

7th step + enzyme

A

3-phosphoglycerate to 2-phosphoglycerate

phosphoglycerate mutase

25
Q

8th step + enzyme

A

phosphoglycerate to phosphoenolpyruvate with release of water

enolase

26
Q

9th step + enzyme

A

phosphoenolpyruvate to pyruvate

ADP to ATP

Pyruvate kinase

27
Q

How many products for one molecule of glucose?

A

2x pyruvate

2 xATP

2x NADH

28
Q

What happens to pyruvate in the aerobic pathway?

A

TCA cycle, oxidative phosphorylation

29
Q

What happens to pyruvate in the anaerobic pathway?

A

pyruvate forms lactate, using NADH

30
Q

Which muscle fibres require glycolysis the most?

A

skeletal muscle type IIb (fast twitch fibres)

31
Q

Why is the phosphorylation of glucose in the first step so important?

A

Forms G6P which then maintains low glucose concentration in the cell, promoting continuous transport of glucose into the cell through plasma membrane transporters

also prevents glucose from leaking out, as the cell lacks transporters for G6P

hexokinase is inhibited by its product

32
Q

Difference in Km between hexokinase and glucokinase

A

glucokinase has a lower affinity for glucose, with the Km in the vicinity of normal glycemia

33
Q

Importance of second stage

A

GGP converted into fructose-6-phosphate

allows the reaction to drive forward because of low conc of F6P, which is constantly consumed in the next stage of glycolysis

isomerisation to a keto sugar is necessary for the carbanion stabilisation

34
Q

What happens if F6P concentration is high? + why

A

reaction readily runs in reverse, explained by Le Chatelier’s Principle

35
Q

Importance of third step

A

the glycolytic process becomes irreversible, as phosphofructokinase 1 is coupled to the hydrolysis of ATP (an energetically favourable step)

forms the rate limiting step

second phosphorylation event allows the formation of two charged groups, ensuring the prevention of free diffusion from the cell

destabilising the molecule, to allow next step to happen with ease

36
Q

What inhibits PFK?

A

A high ratio of ATP to ADP

H+ allosterically

37
Q

what activates PFK?

A

Fructose 2,6-bisphosphate, which is also produced from fructose 6-phosphate by PFK1

more F6P leads to more F-2,6-BP, whose binding increases the affinity of PFK1 for F6P and minimises inhibitory effect of ATP

38
Q

Pyruvate kinase function

A

catalyses last step in glycolysis

transfer of phosphate group from phosphoenolpyruvate to ADP, to produce one pyruvate and one ATP

39
Q

Two conformations of pyruvate kinase + what binds

A

R state- high substrate affinity, stabilised by PEP and fructose 1,6-bisphosphate

T state- inactivated form, low substrate affinity, bound and stabilised by ATP and alanine- causing the phosphorylation of pyruvate kinase and inhibition of glycolysis

40
Q

What is the cofactor? + experiment that confirmed this

A

magnesium 2+

in yeast cells, interaction of yeast pyruvate kinase with PEP and allosteric effector fructose 1,6-bisphosphate was shown to be enhanced by presence of MG2+

41
Q

How does Fructose -1,6-bisphosphate allow a feed forward mechanism?

A

FBP is a glycolytic intermediate produced early on in the reaction

binds to allosteric binding site at domain C of pyruvate kinase and changes the conformation of the enzyme

the higher the conc of FBP, the greater the allosteric activation and the magnitude of pyruvate kinase activity

42
Q

What process is able to utilise pyruvate to form new proteins?

A

Transamination

43
Q

Explain transamination

A

chemical reaction that transfers an amino acid group to a ketoacid to form new amino acids.

alanine transaminase catalyses the addition of a nitrogen group (from alpha amino acid) to pyruvate to form a ketoacid and then form alanine

44
Q

Glycerol-3-phosphate shuttle definition

A

mechanism that regenerates NAD+ from NADH

45
Q

Stages of using galactose as a fuel

A
  1. galactose to galactose 1-phosphate (ATP to ADP) catalysed by galactokinase
  2. galactose 1-phosphate uridyltransferase then catalyses the conversion into glucose 1-phosphate
  3. glucose-1-phosphate isomerises and forms glucose-6-phosphate, which is then able to enter the glycolytic pathway
46
Q

stages of using fructose as a fuel

A
  1. fructose becomes fructose 6-phosphate, catalysed by hexokinase

able to enter the pathway

47
Q

galactosaemia definition

A

accumulation of galactose in blood, cannot be metabolised properly

Metabolism (13 decks)

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