Lecture 28: GLUCOSE AS A FUEL MOLECULE - GLYCOLYSIS Flashcards
What happens to glucose in glycolysis?
It is oxidised
Where is glucose found?
In all organisms (animals, fungi, plants and bacteria)
Where is glycolysis usually in eukaryotes?
Usually cytoplasmic (other pathways are in the mitochondria)
What cells can use glucose?
All cells can use glucose but some rely on/preferentially use it
What is glucose an essential fuel for?
Red blood cells because they don’t have mitochondria and so lack the other pathways
Where is glucose the favoured fuel?
In the brain and eyes
What is the energy requirement of the brain?
High - human brain requires around 120g of glucose per day
Do brain cells have mitochondria?
Yes
What are the theories as to why glucose is the favoured fuel in the brain?
Supply and safety
What is involved in the supply theory?
Glucose easily crosses the blood-brain barrier (through thick blood vessels) but fats do not
What is involved in the safety theory?
A high level of fatty acid metabolism is dangerous. Relying on mitochondria risks anoxia (low oxygen) and production of reactive oxygen species (damaging)
Why is glucose favoured in the eye?
Because blood vessels (bringing oxygen) and mitochondria would refract light in the optical path (lens, cornea) to retina interfering with our vision
What do white muscle cells use?
Glucose (sprinting)
What do red muscle cells use?
Fats (endurance)
What happens in glycolysis?
Glucose (6C) is split to form 2 pyruvate (3C) to conserve/extract energy in ATP and NADH. Pyruvate may be further metabolised
What are the two phases of glycolysis?
Energy investment and energy payoff
What happens in the energy investment phase?
Activation of glucose - getting the molecule into a form so that energy can be captured. Uses 2xATP
What happens in the energy payoff phase?
Make 4ATP and 2NADH
When does the splitting of the molecules occur?
At the end of the investment phase
What is formed from splitting the molecule?
2 different 3C molecules. After a conversion, both are processed in the same way
What is the reaction of glucose to glucose-6-phosphate (G-6-P)?
The first activation of glucose which is coupled to ATP hydrolysis (delta G = -16kJ/mol)
What is the reaction of glucose-6-phosphate (G-6-P) to fructose-6-phosphate (F-6-P)?
A rearrangement (delta G = +1.6kJ/mol). It is driven froward in the reaction because the reactant (G-6-P) is constantly being formed and the product (F-6-P) is constantly being used
What is the reaction of fructose-6-phosphate to fructose-1,6-biphosphate (FBP)?
2nd activation of glucose by adding a phosphate coupled to ATP hydrolysis (delta G = -14kJ/mol)
What is the reaction of FBP to dihydroxyacetone phosphate and glyceraldehyde-3-phosphate (G-3-P)?
The splitting/aldolase reaction. 1x 6C, 2P to 2x 3C, 1P
What does triosephosphate isomerase do?
Converts between the two products of splitting. G-3-P is used in the pathway
What are the pathways for ATP synthesis?
Substrate level phosphorylation and oxidative phosphorylation
What happens in substrate level phosphorylation?
Direct (A+ADP»_space; B+ATP). Energy comes from the substrate
What happens in oxidative phosphorylation?
Indirect (reduced coenzymes)
What is one way to release the energy to drive a substrate level phosphorylation?
To cleave high energy phosphoanhydride bond on the substrate but we add a phosphate in the activation so what is the gain?
What is a key reaction for making an ATP profit?
Oxidation of glyceraldehyde-3-phosphate to 1,3-biphosphoglycerate. NAD+ is reduced and provides the oxidising power and so the addition of the phosphate powered by the oxidation of G-3-P does not require ATP
What is in the first substrate level phosphorylation?
The #1 carbon phosphate of 1,3-BPG is very reactive and so removal of the phosphate by phosphoglycerate kinase releases energy (delta G = 49.3 kJ/mol) that is used fro substrate level phosphorylation (ADP +PI >ATP = +30 kJ/mol, overall = -19.3 kJ.mol). It is the phosphate from the substrate used to make ATP
What does arsenic do to glycolysis?
it poisons it as arsenate substitutes for phosphate. G-3-P >1-Arseno-3-phosphoglycerate>3PG
What does arsenate do?
It is unstable and so hydrolyses spontaneously by energy which is not captured. ATP is not synthesised by phosphoglycerate kinase and there is no net gain of energy in glycolysis
What are the steps after the first substrate level phosphorylation?
Rearrangements to get the molecule into a form that enables the following reactions
What happens in the second substrate level phosphorylation?
removal of phosphate from PEP to make pyruvate releases energy (delta G = -61.9 kJ/mol) that is used in substrate level phosphorylation (ADP + P1 > ATP, delta G=+30 kJ/mol). Overall delta g = -31.9 kJ/mol. The phosphate is used to make ATP
What is the overall formula for glycolysis?
Glucose + 2NAD+ + 2ADP + 2Pi»_space; 2 pyruvate + 2NADH + 2ATP + 2H+
What is the overall delta G for glycolysis?
-73.3 kJ/mol so the pathway is energetically favourable
what happens to pyruvate in aerobic conditions?
Aerobic oxidation. Pyruvate is converted into acetyl-CoA to be further metabolised int he citric acid cycle
Where is pyruvate converted into Acetly-CoA?
In the mitochondrial matrix
What is the enzyme which concerts pyruvate to Acetyl-CoA?
Pyruvate dehydrogenase which is a multi enzyme complex with lots of cofactors/enzymes
What is the net reaction of converting pyruvate to acetyl-CoA?
Oxidative decarboxylation
What happens with the energy from oxidation of pyruvate?
It is captured in NADH and used to add coenzyme a (CoA)
What is the delta G of pyruvate oxidation?
-33.4kJ/mol
What happens to pyruvate in anaerobic (low oxygen) conditions?
It is converted to lactate by lactate dehydrogenase using energy captured in NADH (energy is lost).The lacteal causes muscle fatigue
Why does the anaerobic pathway of oxidation occur?
There are low concentrations of enzymes in cells asn during anaerobic oxidation coenzymes are oxidised (regenerated) in oxidative phosphorylation
What happens is the lactate dehydrogenase reaction?
NAD is oxidised to produce sufficient NAD+ for the glyceraldehyde-3-phosphate dehydrogenase reaction so glycolysis can continue to generate ATP
What happens to pyruvate in anaerobic conditions in yeast?
Anaerobic alcoholic formation - pyruvate is converted to ethanol and carbon dioxide to recycle NAD+
