Lecture 24 - Glucose as a fuel molecule #2 Flashcards
What are the basic steps of Glycolysis?
- Splitting of glucose (one 6 Carbon glucose to two 3 Carbon pyruvate molecules)
- Energy is conserved in ATP and NADH
- Pyruvate may be further metabolised aerobically or anaerobically
What is the activation of glucose?
Getting the molecule into a form so energy can be captured - this requires an energy input
What are the two phases of glycolysis?
- Energy Investment phase
- Energy Payoff phase
What happens during the energy investment phase?
Energy is used/invested in making the glucose molecule ready for splitting
The molecule is split (1X6C to 2X3C) at the end of the investment phase
What two molecules are glucose split into during the energy investment phase?
Pyruvate
How many ATP are spent during the energy investment phase?
2 ATP
What happens during the energy payoff phase?
4 ADP turns into 4 ATP
2 NAD+ turns into 2 NADH
What is the first key reaction for the activation of glucose?
Glucose + phosphate ➔ glucose-6-phosphate + H2O
What enzyme adds a phosphate onto glucose
Hexokinase
Is the first key reaction for the activation of glucose energetically favourable?
No, has +ve ΔG, but is required for glucose to be used as a fuel molecule
How is this non-spontaneous first key reaction for the activation of glucose carried out?
By the coupling of the reaction (+ΔG) to ATP hydrolysis(-ΔG). Allowing the overall reaction to be spontaneous (-ΔG)
What is the overall coupled reaction?
Glucose + ATP ➔ glucose-6-phosphate + ADP
What is the second key reaction in the activation of glucose?
Glucosephosphate isomerase - rearrangement from glucose-6-phosphate into fructose-6-phosphate (F-6-P) (+ΔG)
What is the third key reaction in activation of glucose?
Phosphofructokinase - 2nd activation of glucose that uses ATP hydrolysis to convert Fructose-6-phosphate into Fructose-1,6-biphosphate (FBP)
(addition of second phosphate)
What occurs during the splitting (aldolase) reaction?
Occurs after the third key step of glucose activation.
FBP is split by aldolase forming DHAP, and G-3-P
What phase of glycolysis is G-3-P used?
In the energy payoff phase
What is the consequence of G-3-P being used up in the energy payoff phase?
The G-3-P concentration is low which drives the reaction from DHAP to G-3-P
What enzyme catalyses the rearrangement of DHAP into G-3-P?
Triose phosphate isomerase
What is substrate level phosphorylation? (SLP)
The direct use of energy from a substrate molecule to drive the synthesis of ATP (or equivalent)
What is one way to release energy to drive a SLP?
By the cleavage of a high-energy phosphate ester bond on a substrate
What is NAD?
A coenzyme required by some enzymes that catalyse redox reactions
What is NAD derived from ?
Niacin (vitamin B3)
What are the two forms of NAD?
NAD+(the oxidised form)
NADH(the reduced form)
What is the importance of oxidising G-3-P?
It is a reaction for making an ATP profit
How does oxidising G-3-P help make ATP profit?
it powers the addition of a phosphate to itself forming 1,3-BPG
Does the addition of a phosphate require ATP?
No, phosphate from solution added to substrate
What is reduced as G-3-P is oxidised?
NAD+
Which carbon on 1,3-BPG is very reactive?
The first one
What is 1,3-BPG converted into?
3PG
What does occurs during the reaction from 1,3-BPG to 3PG?
Phosphate is cleaved from the 3-BPG by phosphoglycerate kinase this releases energy which is coupled with substrate level phosphorylation producing some ATP
How does arsenic poison glycolysis?
Binds to the phosphoglycerate and formed 1-Arseno-3-phosphoglycerate instead of 1,3-BPG. So no ATP is synthesised by the phosphoglycerate kinase.
What then happens to 3PG?
Rearranged to make 2PG, and then 2PG is rearranged to make PEP. This puts the molecule in a form that enables the next reactions
What happens to PEP?
A phosphate is cleaved off of it by Pyruvate kinase, releasing energy which is coupled to the second substrate level phosphorylation in order to produce ATP
How is the overall change in Gibbs free energy throughout glycolysis?
Negative so pathway is energetically favourable (some energy is converted into heat)
What happens in the citric acid cycle?
Aerobic oxidation - Pyruvate is converted to acetyl-CoA to be further metabolized
in the citric acid cycle
What is Coenzyme A (CoA) derived from?
pantothenic acid (vitamin B5)
Is CoA a carrier of electrons?
No (not reduced/oxidized)
What does CoA carry?
Acyl groups - (2 C to long chains)
What are the two forms of CoA
free coenzyme A: CoASH
acyl group attached: Acyl-CoA (AcCoA)
Where does the aerobic oxidation of pyruvate occur?
In the mitochondrial matrix.
What enzyme complex is involved in the aerobic oxidation of pyruvate?
Pyruvate dehydrogenase complex.
What type of reaction is the conversion of pyruvate to Acetyl-CoA?
Oxidative decarboxylation.
What molecule is released during the decarboxylation of pyruvate?
CO₂ (carbon dioxide).
What is added to the two-carbon chain after pyruvate is oxidized?
Coenzyme A (CoA).
What happens to pyruvate in the pyruvate dehydrogenase reaction?
Pyruvate is oxidized, releasing energy that is captured in NADH.
Which cofactors or coenzymes are involved in the pyruvate dehydrogenase reaction?
TPP (thiamine pyrophosphate), FAD, lipoic acid, NAD⁺, and Mg²⁺.
What is the overall change in free energy (ΔG°’) for the conversion of pyruvate to Acetyl-CoA?
ΔG°’ = -33 kJ/mol.
What happens during anaerobic glycolysis?
Instead of entering the citric acid cycle, pyruvate becomes lactate from the enzyme lactate dehydrogenase
What does lactate do?
Causes muscle fatigue
What happens to the energy captured in NADH during the lactate dehydrogenase reaction?
The energy is lost
How is the concentration of coenzymes in cells?
Low
When are coenzymes oxidised during aerobic oxidation?
In oxidative phosphorylation
What does lactate formation allow?
Lactate formation allows for the regeneration of NAD+ as lactate dehydrogenase
reaction oxidizes NAD meaning that there is enough NAD for the G-3-P dehydrogenase reaction
