Glycolysis Flashcards
Glycolysis definition
the first step in the breakdown of glucose to extract energy for cellular metabolism
Glucose
- The most convenient
- Glucose is the most important carbohydrate
- More than half of all organic compounds is in starch and cellulose, two polysaccharides
- It is our primary source of energy and is oxidised to carbon dioxide and water
- Remember: GOCOWE!
- Glucose + O2 → CO2 + H2O + Energy
- Sometimes it takes another path and ends up as substances e.g. fat
- Cells such as erythrocytes, retina and renal medulla use only glucose as an energy source
- Need glucose for brain to function
- Think: need chocolate to study!
Glycolysis reaction
Glucose + O2 → CO2 + H2O + Energy
Intracellular stages of metabolism
- glycolysis
- citric acid cycle
- electron transfer chain
GLUT 1
- brain
- low Km
GLUT 2
- liver, pancreatic beta cells
- insulin independent
GLUT 3
- brain
- low Km
GLUT 4
- muscle, adipose tissue
- insulin dependent
GLUT 5
- gut
- fructose dependent
How is glucose transported into cells
via passive transport a.k.a. facilitated diffusion, through glucose transporters
Action of GLUT 1
- A conformational change is triggered by the binding of glucose to the outside of the cell. This causes the binding site to face inwards.
- Glucose is then released into the cell.
- This causes another conformational change which regenerates the binding site back onto the outside of the cell
Glycolysis reaction
glucose + 2 ADP + 2 Pi + 2 NAD+ → 2 pyruvate + 2 ATP + 2 H2O + 2 NADH + 2 H+
Stages of glycolysis
- Glucose is trapped and destabilised.
- Two 3-carbon molecules are formed.
- Generation of ATP
Two main cellular requirements
- ATP production
- Provision of building blocks for synthetic reactions
Control points in glycolysis
Enzymes act as potential control points by catalysing irreversible reactions.
Hexokinase
Glucose + ATP → glucose 6-phosphate + ADP + H+
△ G = -33.5 kJ mol-1
Pyruvate Kinase
phosphoenolpyruvate + ADP + H+ → pyruvate + ATP
△ G = -16.7 kJ mol-1
Phosphofructokinase
fructose 6-phosphate + ATP → fructose 1,6-bisphosphate + ADP + H+
△ G = -22.2 kJ mol-1
The key enzyme in control of glycolysis
Phosphofructokinase
Negative modulators
- ATP
- Citrate (early intermediate in the citric acid cycle; biosynthetic precursors are abundant)
- H+ (prevents excessive lactic acid formation)
- a negative feedback loop to maintain homeostasis
Positive modulators
- AMP
- Fructose 2, 6-bisphosphate
Energy charge
- energy charge = the ATP/AMP ratio
The cell is fully charged if…
all adenylate nucleotides are in the shape of ATP
The cell is discharged if…
the cell only contains AMP and Pi
So why is AMP and not ADP the positive regulator?
BECAUSE if ATP is readily used up (ATP → ADP + Pi) then adenylate kinase can use some of the energy in ADP (2 ADP → ATP + AMP).
Glucose transport into cell
- Glucose is not readily diffusible through plasma membrane, it is too big!
- Not lipophilic enough
- Therefore, requires a transporter, specifically, a symporter
- It utilises a Na gradient
- Inside cell high concentration of potassium and low concentration of sodium
- Outside cell low concentration of potassium and high concentration of sodium
- NA/K pump is an antiporter, transports Na out against concentration gradient and K in against its concentration gradient
- Energetically unfavourable reaction
- Opposite of osmosis
- Maintains this balance at an energy cost
- Glucose and Na move together with concentration gradient – doesn’t require energy.
Glucose transport into cells: passive or active transport?
- passive (facilitated diffusion)
What does Low Km mean?
the receptor has a high affinity (binds readily)
Why does the brain have a low Km?
it needs to be able to bind to even very low concentrations of glucose for survival
Stages of glucose transport into cell
- A conformational change is triggered by the binding of glucose to the outside of the cell. This causes the binding site to face inwards.
- Inside has a low concentration of glucose therefore glucose will be released
- The off-rate is higher than the on-rate
- Glucose is then released into the cell.
- This causes another conformational change which regenerates the binding site back onto the outside of the cell.
Stage 1 of glycolysis
- Glucose is trapped and destabilised.
- C6 of Glucose is phosphorylated to form glucose 6-phosphate
- Isomerised to produce fructose 6-phosphate (more symmetrical molecule than glucose)
- Symmetry is favourable
- Phosphorylate C1 to make more symmetrical, forming fructose 1,6 – triphosphate
- Kinase phosphorylates
- A hexokinase
- Got a phosphate, rearrange it, you get another phosphate!
Stage 2 of glycolysis
- Two 3-carbon molecules are formed
- Carbon 2 and carbon 3 are swapped around
- Can be readily swapped by an enzyme called isomerase
- G3P very rapidly converted into something else and so it disappears
- All of this reaction is driven to completion by G3P
Stage 3 of glycolysis
- Generation of ATP
- Control Points in Glycolysis
- G3P gets further phosphorylated
- Phosphates used to make ATP
- Isomerisation reactions occurring
