Glycolysis Flashcards

1
Q

What is glycolysis ?

A
  • it is the conversion of glucose to pyruvate
  • it doesn’t require oxygen
  • takes place in the cytosol of eukaryotes
  • it is an ancient pathway employed by a wide range of organisms
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2
Q

Why do red blood cells only use glucose as a fuel ?

A

They cannot use anything else as they do not contain any mitochondria

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3
Q

What is the most important and common fuel for most cells ?

A

Glucose

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4
Q

How many stages does glycolysis have ?

A

It is a 2 stage process

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5
Q

Summarise the first stage of glycolysis

A
  • it is the trapping and destabilising stage of glucose in order to produce 2 3C molecules
  • it has 5 steps
  • requires 2 ATP molecules per glucose
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6
Q

Summarise the second stage of glycolysis

A
  • it involves the oxidation of the 3C molecules into pyruvate
  • it has 5 steps
  • 4 molecules of ATP are generated per glucose
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7
Q

Why can glucose not cross the plasma membrane without help ?

A

glucose is hydrophilic and so it enters the ell via facilitated diffusion through specific transport proteins

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8
Q

What are the 3 main glucose transport proteins ?

A
  • GLUT 2
  • GLUT 3
  • GLUT 4
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9
Q

Describe GLUT 2

A
  • it is insulin dependent
  • has a very low affinity for glucose
  • found in the liver and pancreatic beta cells
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10
Q

Describe GLUT 3

A
  • used by most tissues and the brain
  • has a high affinity for glucose
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11
Q

Describe GLUT 4

A
  • found in skeletal muscle
  • most of these transport proteins are found in the cytosol of the skeletal muscles and not on the surface
  • insulin will send a signal to the muscle and allow the translocation of the GLUT4 transporters to the surface of the muscle and so the muscle can grab the glucose and utilise it
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12
Q

Describe step 1 of stage 1 of glycolysis

A
  • glucose enters the cell by facilitated diffusion through specific transport proteins
  • once in the cell glucose is trapped by phosphorylation
  • a hexokinase enzyme will use a phosphate group from ATP to phosphorylate glucose into glucose 6 - phosphate
  • glucose 6 - phosphate is negatively charged and so it cannot diffuse freely out of the cell
  • this begins the destabilisation process of glucose
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13
Q

What type of enzyme is hexokinase ?

A

it is a regulatory enzyme

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14
Q

Describe step 2 and 3 of stage 1 of glycolysis

A
  • glucose 6 - phosphate is isomerised into fructose 6 - phosphate by the enzyme phosphoglucose isomerase
  • a second phosphorylation reaction will take place where fructose 6 - phosphate is phosphorylated to fructose 1,6 - bisphosphate
  • this is done by the enzyme phosphofructokinase
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15
Q

What type of enzyme is phosphofructokinase ?

A
  • it is a regulatory enzyme
  • it is inhibited by ATP, citrate and H+ ions
  • it is stimulated by AMP, ADP and fructose 2,6 - bisphosphate in the liver
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16
Q

Describe step 4 and 5 of stage 1 of glycolysis

A
  • fructose 1,6 - phosphate is split into 2 triose phosphates : DHAP and glyceraldehyde 3 - phosphate
  • this is done by the enzyme aldose
  • glyceraldehyde 3 - phosphate (GAP) is on the direct pathway to be converted to pyruvate but DHAP is not and so it is converted to GAP by the enzyme triose phosphate isomerase
17
Q

Describe step 1 of stage 2 of glycolysis (step 6)

A
  • glyceraldehyde 3 - phosphate is oxidised and phosphorylated by the enzyme G3-P dehydrogenase
  • NAD+ is reduced to NADH
  • the resulting intermediate is 1,3 - bisphosphoglycerate and it is an acyl phosphate so it has a high energy bond
18
Q

What is the clinical significance of G3-P dehydrogenase ?

A
  • mercury which is found in amalgam fillings inhibits GAPDH by binding to the sulfhydryl group within the enzyme and so it can inhibit glycolysis
  • arsenate also inhibits GAPDH by substituting for a phosphate group
19
Q

Describe step 2 of stage 2 of glycolysis (step 7)

A
  • ATP is generated from 1,3 - bisphosphoglycerate by substrate level phosphorylation
  • the enzyme phosphoglycerate kinase will produce 3 - phosphoglycerate
20
Q

Describe step 3,4 and 5 of stage 2 of glycolysis (step 8,9 and 10)

A
  • the phosphoryl group on 3 - phosphoglycerate shifts to the C2 position and makes 2 - phosphoglycerate using the enzyme phosphoglycerate mutase
  • 2 - phosphoglycerate will be dehydrated by the enzyme enolase to form phosphenolpyruvate
  • phosphenolpyruvate is dephosphorylated by pyruvate kinase to make pyruvate and this generates ATP
21
Q

What type of enzyme is pyruvate kinase ?

A
  • it is a regulatory enzyme
  • inhibited by ATP
  • activated by fructose 1,6 - bisphosphate
22
Q

Describe the catabolic fates of pyruvate in aerobic conditions

A
  • pyruvate will enter the mitochondria and is oxidised to acetyl CoA
  • NADH cannot enter the mitochondria and so NAD+ is regenerated indirectly by oxidative phosphorylation using specific shuttles
  • the shuttle systems are used to take electrons from the cytosol and move them in to the mitochondria so they can be used in oxidative phosphorylation to generate NADH
23
Q

Describe the catabolic fates of pyruvate in anaerobic conditions

A
  • pyruvate is reduced to lactate by the enzyme lactate dehydrogenase
  • NADH will be oxidised to NAD+ and so glycolysis can carry on
  • this takes place in bacteria and skeletal muscles during exercise
  • yeast will form ethanol under anaerobic conditions
  • pyruvate will be decarboxylated to acetaldehyde
  • acetaldehyde is reduced to ethanol and NADH is oxidised to NAD+
24
Q

Describe the enzyme pyruvate dehydrogenase

A
  • it is a multienzyme complex of 3 kinds of enzymes
  • there are 5 coenzymes associated with it of which 3 are catalytic cofactors (thiamine pyrophosphate, lipoic acid and FAD) and 2 are stoichiometric cofactors (CoA and NAD+)
  • regulated allosterically and by covalent modification
  • it links glycolysis and the krebs cycle
25
Q

Describe the clinical significance of pyruvate dehydrogenase

A
  • mercury which is found in amalgam fillings and arsenic both inactivate pyruvate dehydrogenase
  • causes neurological symptoms
26
Q

How does sucrose enter glycolysis ?

A
  • sucrose is hydrolysed into its monosaccharides glucose and fructose by the enzyme sucrase
  • glucose will enter glycolysis
  • fructose needs to be metabolised
27
Q

How is fructose metabolised so it can enter glycolysis ?

A
  • in adipose tissue hexokinase will phosphorylate fructose to fructose 6 - phosphate which is an intermediate of glycolysis
  • in the liver fructose will enter glycolysis via the fructose 1 - phosphate pathway
28
Q

Describe the fructose 1 - phosphate pathway

A
  • fructose is hydrophilic so will enter the cell via facilitated diffusion and transport proteins
  • fructose is then phosphorylated by fructokinase into fructose 1 - phosphate
  • fructose 1 - phosphate will split into 2 3C molecules by the enzyme fructose 1 - phosphate aldolase
  • the 3C molecules are glyceraldehyde and DHAP
  • triose kinase will phosphorylate glyceraldehyde into glyceraldehyde 3 - phosphate
  • DHAP and glyceraldehyde 3 - phosphate are intermediates of the glycolysis pathway
29
Q

What is fructosuria ?

A
  • it mild autosomal recessive disorder
  • a lack of fructokinase means fructose will remain the gut leading to diarrhoea
  • fructose will be present in the urine
30
Q

What is hereditary fructose intolerance ?

A
  • a very lethal condition
  • lack of fructose 1 - phosphate aldolase will severely reduce the production of ATP
  • ATP driven ion channels will not function and the cells will begin to swell
  • it can cause severe liver damage and hypoglycaemia
  • it can lead to death in young children
  • must avoid sucrose and so the teeth will generally be better
31
Q

How does lactose enter glycolysis ?

A
  • lactose is hydrolysed into its monosaccharides by the enzyme lactase
  • glucose will enter glycolysis
  • galactose will need to be converted to glucose before it can enter
32
Q

Describe the conversion of galactose to glucose

A
  • galactokinase will phosphorylate galactose into galactose 1 - phosphate to trap it in the liver
  • galactose 1 - phosphate combines with UDP glucose to form UDP - galactose and glucose 1 - phosphate
  • glucose 1 - phosphate can then enter glycolysis
  • UDP - galactose is epimerised into UDP - glucose which can then be used in the steps above
33
Q

What is lactose intolerance ?

A
  • a deficiency in the lactase enzyme
  • in a lactase deficient person lactose is degraded in the gut by bacteria producing lactic acid and other gases
  • lactic acid draws water into the gut causing diarrhoea
34
Q

What happens in response to deficiency in galactokinase ?

A
  • a lack of the enzyme will lead to a build up of galactose in the body
  • galactose is fairly reactive and so it will bind to where it shouldn’t
  • it can be converted into galactitol which will cause the development of cataract in the eye
35
Q

What is the net yield of ATP molecules in the glycolysis pathway ?

A
  • there is a net yield of 2 ATP
  • 2 ATP molecules are used and 4 ATP molecules are generated
36
Q

What are the 3 regulatory enzymes of glycolysis ?

A
  • hexokinase
  • phosphofructokinase
  • pyruvate kinase