Regulation of Glycolysis and TCA Flashcards
What type of reaction is used to break down glucose?
A series of redox reaction
What are redox reactions?
Oxidation reduction reactions
What does it mean to be oxidised?
It means the molecule has lost electrons
What does it mean to be reduced?
It means the molecule has gained electrons
How does a redo reaction help make ATP
Redox reactions transfer energy (stored in the glucose bonds) to electron carriers
What is an electron carrier?
A molecule that transports electrons during cellular respiration
Give examples of electron carriers?
NAD
FAD
How is energy stored using NAD?
Energy is stored by adding 2 electrons to NAD+:
NAD+ + 2H-> NADH + H+
How is the stored energy in NAD released?
Energy stored is released when FADH2 and NADH are oxidised to NAD+ and FAD
FAD + 2H ->FADH2
What is the net profit of ATP following glycolysis?
2 ATP
What is the net profit of NADH following glycolysis?
2 NADH
What is the net profit of ATP following TCA?
2 ATP
What is the net profit of NADH following TCA?
6 NADH
What is the net profit of FADH following TCA?
2 FADH
What happens under anaerobic conditions to yeast?
Under anaerobic conditions
yeast can not go through
the TCA and ETC
So fermentation occurs
The regeneration of which molecule is important to maintain glycolysis?
The regeneration of NAD+
When does fermentation occur in skeletal muscles?
When the muscles are deprived of oxygen
Name the three stages of AEROBIC respiration
- Glycolysis
- TCA
- Electron transport chain
What happens to the TCA when theres a shortage of oxygen?
The TCA does not use oxygen but it does stop in the absence of oxygen because we run out of NAD+ and FAD
Which stage is common in both aerobic and anaerobic respiration?
Glycolysis
What is produced as a by product in anaerobic respiration in the skeletal cells ?
Lactic acid
Briefly go through glycolysis
Glucose is converted into pyruvate which is converted into acetyl coA
The net ATP yield form this reaction is 2
What is the anaerobic pathway?
It is the pathway where simple sugars (glucose) are converted into ethanol and carbon dioxide without the presence of oxygen
Where does fermentation occur in yeast cells?
Occurs in the cytosol of yeast cells
Following glycolysis what steps occur to convert pyruvate into ethanol?
- Pyruvate undergoes decarboxylation (CO2 released) aided by pyruvate decarboxylase
- This forms acetaldehyde
- acetaldehyde reacts wit alcohol dehydrogenase to form ethanol
Name the enzyme that aids pyruvate decarboxylation
pyruvate decarboxylase
During glycolysis in yeast which reactions are absent
Theres no net oxidation reduction reaction
What is the difference between ATP production in anaerobic and aerobic glycolysis?
Glycolysis is maintained in anaerobic glycolysis but only a fraction of energy is produced
What happens to the ethanol and carbon dioxide produced in fermentation in yeast?
They are waste product and can be toxic to the yeast cell
What can happen when you distill ethanol from yeast and is this good or bad?
You can get methanol which is toxic
How do we cure methanol poisoning
Alcohol
What are the three stages of aerobic respiration
- Glycolysis (yields 2 ATPs)
- TCA cycle (Yields 2 ATPs)
- Electron transport chain (Yields 28 ATPs)
Why does a shortage of oxygen affect the TCA cycle when oxygen isn’t used up in TCA?
The TCA doesn’t use oxygen but it runs out of NAD+ and FAD when oxygen is lacking
Which stages of aerobic reparation are affected when theres a lack of oxygen?
- TCA as theres no NAD and FAD
2. Electron transport chain as oxygen is the final electron acceptor
What role does oxygen have in the electron transport chain?
It is the final electron acceptor
Which process is common in both anaerobic and aerobic respiration?
Glycolysis
Where does glycolysis occur in the cell?
In the cytoplasm
What are the final products of glycolysis
2 ATPs
2 NADHs
2 pyruvate molecules
What happens when the body doesn’t have enough oxygen but needs to keep moving (eg when exercising)
The cells begin to do lactic acid fermentation
What is lactic acid fermentation
The resection of Pyruvate by NADH to produce lactate (aided by lactate dehydrogenase)
Name the enzyme involved in the reduction of pyruvate into lactate
Lactate dehydrogenase
What is produced when pyruvate is reduced into lactate and what does this by product do?
NAD+ form which re enters glycolysis
Which 2 monosaccharides is lactose made up of?
- Glucose
2. Galactose
What happens if you are lactose intolerant?
You don’t produce enough lactose enzyme to break down all the lactose so the lactose remain unbroken end persist with in your gut and are fermented by bacteria
Give some symptoms of lactose intolerance
- Farting
- Diarrhoea
- Bloating
- Stomach cramps and pains
- Stomach rumbling
- Feeling sick
What is Galactosemia?
It is an inherited autosomal recessive disorder and can be screened for at birth
What can Galactosemia lead to?
Can cause:
- enlargement of the liver
- Central nervous system failure
What is Galactosemia caused by?
Due to a deficiency of galactose 1-phosphate uridyl transferase
What does having a deficiency in galactose 1-phosphate uridyl transferase mean?
Means you can’t break down galactose
Why is Galactosemia screened for at birth?
As babies main source of food is milk so if they have this disease they won’t be able to digest milk
Describe the eyes of a patient who is suffering from Galactosemia
May develop cataracts in their eyes
Why might patients with Galactosemia develop cataracts in their eyes?
If lactose cannot be brown down instead Aldose reductase converts the galactose into an alcohol which leads to cataracts
Where do bacteria in deep dental plaque get their energy from and why?
Get their energy through glycolysis as Dental plaque deep layers are highly anaerobic
How does fluoride help fight dental plaque?
As floride can inhibit the enzyme enolase (needed in glycolysis) thus stopping glycolysis so bacteria can’t get any energy
Briefly summarise glycolysis
- Bacteria reacts with hexokinase forming glucose 6-phosphate (uses ATP)
- G6P reacts reversibly with phosphglucise isomerase to Forman fructose 6-phosphate
- fructose 6-phosphate reacts with PFK to form fructose 1-6 biphosphate
- fructose 1-6 biphosphate reacts with aldose to form GAP and DHAP
- GAP then produces 2 NADHs and 1,3- bisphophate
- 1,3- bisphophate reacts with phophuglycerate kinase adncascades down to form 2-phosphoglycerate
- Phosphoglycerate reacts with enclave to form 2 ATPs and 2 pyruvate molecules
Which molecule do we need to be able to enter the TCA cycle?
Acetyle CoA
How is pyruvate inverted into Acetyl CoA?
Via the enzyme pyruvate dehydrogenase
How does acetyl CoA feed into the citric acid cycle?
Via a reaction with oxyl acetate
What percentage of our genes are used to regulate metabolism
12% (2050/20,000)
What are the different ways we can regulate metabolism?
- Genetic regulation
2. Regulating enzyme concentraion
How does genetics regulate metabolism?
Genetics determines the concentration of enzymes in a cell
Name the 4 ways we can regulate enzymes in a cell
- Association with regulatory proteins
- Sequestration (compartmentalisation)
- Allosteric regulation
- Covalent modification
What is allosteric regulation enzymes?
It is when an inhibitor binds to our enzymes and actively changes the shape of the enzyme rendering it useless
How does covalent regulation help regulate active enzyme concentration in a cell?
Covalent modification changes the covalent structure of an enzyme changing its structure
How does Association with regulatory proteins help regulate active enzyme concentration in a cell?
This limits the amount of enzymes that can associate with in our reactions
How does Sequestration (compartmentalisation) help regulate active enzyme concentration in a cell?
This alters the accessibility of the enzyme with the substrate
How is Sequestration (compartmentalisation) achieved?
Achieved through membranes within our cells as they only let what is needed for the ruction into the cell
Name the 3 enzymes that can be regulated in glycolysis
- Hexokinase
- Phosphofructokinase
- Pyruvate kinase
Name the 3 enzymes that can be regulated in the TCA cycle
- Citrate synthase
- Isocitrate dehydrogenase
- Alpha ketoglutarate dehydrogenase
What does hexokinase do?
Aids the reaction of glucose into glucose 6-phosphate
What does Phosphofructokinase do?
Aids the reaction of fructose 6-phosphate into fructose 1,6-biphosphate
What does Pyruvate kinase do?
Aids the conversion of phosphoenolpyruvate into pyruvate
How is heoxkinase regulated?
by allosteric feedback inhibition
When do glucose 6-phophate levels increase?
When glucose is inhibited at sites further along the pathway as GGP prevents hexokinase form working
How do glucose 6-phophate inhibit glycolysis?
By preventing hexokinase from working
How does glucose 6-phophate inhibit hexokinase from working
As it results in allosteric feedback inhibition of hexokinase which ultimately changes the structure of hexokinase
The conversion of fructose 6-phosphate into fructose 1,6-biphosphate is metabolically what?
Metabolically irreversible
What inhibits Phosphofructokinase (PFK1)
ATP
Why does an increased concentration reduce the effectiveness of Phosphofructokinase ?
As High concentrations of ATP lower its affinity for fructose-6-phosphate so conversion into fructose 1,6-biphosphate isn’t as effective
What is Phosphofructokinase
An enzyme that is made up of of 4 identical proteins
Name the substrate for Phosphofructokinase
ATP
What increases Phosphofructokinase activity>
ADP and AMP
What is Phosphofructokinase sensitive to other than concentration of ATP, ADP and AMP?
pH
How does pH effect Phosphofructokinase activity?
Acidic conditions reduces the activity of Phosphofructokinase and also prevents excessive formation of lactic acid
How is PFK regulated?
in 2 ways:
- By ATP concentration
- Fructose 2,6-bisphosphate Allosterically regulares fructose 6-phosphate
How is pyruvate kinase regulated?
By allosteric inhibition and covalent modification
Give the chemically signs that there’s lots of energy in a cell
There will be high levels of ATP and acetyl CoA
Name the molecule that activates pyruvate kinase
Fructose 1,6 bisphosphate
How does ATP affect pyruvate kinase?
ATP allosterically inhibits pyruvate kinase
How many forms of pyruvate kinase are there and what are they called?
2 forms:
1, L form
2. M form
What is the L form of pyruvate kinase susceptible to?
Susceptible to covalent modification via phosphorylation
How does blood glucose affect pyruvate kinase?
Low blood glucose means theres more ADP being. made so that ATP can be conserved
In this process phosphate ion is released and forms phosphorylated pyruvate kinase
When the blood glucose level rises the phosphate from phosphorylates pyruvate kinase is removed activating the pyruvate kinase enzyme
Name the regulatory point of the TCA cycle
- The conversion of pyruvate to acetyl CoA
- The conversion of isocitrate into alpha ketogulturate
- The conversion of alpha ketogulturate into succinylcholine coA
Name the enzyme that can be regulated in the TCA cycle?
- Pyruvate dehydrogenase
How is pyruvate dehydrogenase regulated?
In 2 ways:
- Via allosteric regulation
- Via covalent regulation
What does Pyruvate dehydrogenase do?
Aids in the conversion of pyruvate into acetyl CoA
Where do the allosteric regulators of Pyruvate dehydrogenase occur?
- E2 sites
2. E3 sites
What is the E2 site limited by?
Acetyle CoA
What is the E3 site regulated by
NADH
How is the pyruvate dehydrogenase covalently regulated?
When energy is high ATP is dephosphorylated into ADP
This conversion releases a phosphide ion which reacts with pyruvate dehydrogenase inactivating it
Then when energy Is high again the inactive pyruvate dehydrogenase is dephosphorylated to activate the enzyme again
How does acetyl CoA affect pyruvate dehydrogenase?
Increase in acetyl coA negatively affects pyruvate dehydrogenase
This prevents the kerbs cycle from occurring if there too much acetyl coA as the body isn’t in need of a lot energy
State the reaction that occurs in the TCA cycle
Acetyl-CoA + 3NAD+ +FAD+ GDP+ Pi
=>
CO2 +3NADH+ FADH2+ GTP
How is the TCA regulated?
Allosterically
Can the TCA cycle stop?
NO it can be regulated and slowed down depending on substrate availability
What drives tea TCA cycle when the body is subject to starving conditions
Under starving conditions amino acids can be broken down and fed into the TCA cycle as alpha ketogluterate which will speed of the cycle
Name the 3 enzymes that catalyse irreversible reactions in the TCA cycle
- Citrate synthase
- Isocitrate degydrigenase
- Alpha degydrigenase complex
Name the molecule that can allosterically inhibit:
- Citrate synthase
- Isocitrate degydrigenase
- Alpha degydrigenase complex
NADH and ATP
Which molecules can allosterically inhibit citrate synthase?
- NADH
- ATP
- Citrate
- Succinyl CoA
What molecule can activate isocitrate dehydrogenase?
ADP
Name the 3 enzymes in glycolysis the can be regulated
Hexokinase
Phosphofructokinase
Pyruvate kinase
What is Pyruvate dehydrogenase regulated by?
Covalent modification