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
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
3
Q
What is the most important and common fuel for most cells ?
A
Glucose
4
Q
How many stages does glycolysis have ?
A
It is a 2 stage process
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
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
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
8
Q
What are the 3 main glucose transport proteins ?
A
- GLUT 2
- GLUT 3
- GLUT 4
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
10
Q
Describe GLUT 3
A
- used by most tissues and the brain
- has a high affinity for glucose
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
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
13
Q
What type of enzyme is hexokinase ?
A
it is a regulatory enzyme
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
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
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
Describe the clinical significance of pyruvate dehydrogenase
- mercury which is found in amalgam fillings and arsenic both inactivate pyruvate dehydrogenase
- causes neurological symptoms
26
How does sucrose enter glycolysis ?
- sucrose is hydrolysed into its monosaccharides glucose and fructose by the enzyme sucrase
- glucose will enter glycolysis
- fructose needs to be metabolised
27
How is fructose metabolised so it can enter glycolysis ?
- 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
Describe the fructose 1 - phosphate pathway
- 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
What is fructosuria ?
- 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
What is hereditary fructose intolerance ?
- 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
How does lactose enter glycolysis ?
- 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
Describe the conversion of galactose to glucose
- 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
What is lactose intolerance ?
- 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
What happens in response to deficiency in galactokinase ?
- 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
What is the net yield of ATP molecules in the glycolysis pathway ?
- there is a net yield of 2 ATP
- 2 ATP molecules are used and 4 ATP molecules are generated
36
What are the 3 regulatory enzymes of glycolysis ?
- hexokinase
- phosphofructokinase
- pyruvate kinase
Bioenergetics And Transformation
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