TOPIC 3: GLYCOLYSIS Flashcards
Glycolysis occurs where in the fed state
Why glucose?
- Glucose is centrally important molecule for life
- It is rich in potential energy
- Easy for cells to store (starch and glycogen)
- Useful as a building block in cells
- Generates important molecules for other cellular processes (i.e. metabolic precursors)
overview of glycolysis
Hexokinase vs. Glucokinase
- Hexokinase:
o most cells
o Has a K m ~ 0.1 mM (low) high affinity, Vmax gets achieved at very low substrate concentration - Glucokinase
o Active in liver and islet cells of the pancreas
o Is specific for glucose
o Has a K m ~ 10 mM (high) lower affinity for glucose, glucose activity needs to be high before glucokinase activity is saturated
Gycolysis
Converts 1 glucose to 2 pyuvate
Key factors which dictate how a molecule is transported are its
polarity, size and charge.
Simple diffusion
- A passive process
- The unassisted net movement of a solute from a region of high concentration to a region of low concentration
- No protein required to assist as molecule moves solely on the basis of the concentration gradient
- Because membranes have a non-polar interior, simple diffusion only works for gases, and small, non-polar molecules
Facilitated diffusion (aka passive transport)
- A passive process
- Where a protein acts to facilitate the movement of a molecule across a membrane
- Still only moves the molecule down the concentration gradient
- But, facilitated diffusion gets around the hydrophobicity of the membrane interior using the protein
- The protein can either transport or channel the molecule through the hydrophobic region of the membrane.
GLUT transporters
- There are at least 12 glucose transporters (GLUT) in the human genome
- They differ in their kinetics and their tissue specialisation
- However, of the well characterised transporters, all, apart from GLUT5, function to transport glucose from a high concentration to a low concentration (facilitated diffusion)
Why are the intermediates of glycolysis phosphorylated?
- Glucose transport is reversible
1. They can’t traverse the cell membrane
o There are no transporters for G-6-P on the membrane
o Addition of PO 4 3- increases polarity of glucose
o ‘Traps’ glucose in the cell
2. Necessary to form substrate-enzyme complex
o Only recognised by enzyme after phosphorylated
3. Necessary to phosphorylate ADP, yielding a net gain of ATP
ATP production during Glycolysis
+ 2 NADH
Fates of NADH
- Only a limited amount of NAD+ in a cell
- Need to regenerate NAD+, otherwise glycolysis will grind to a halt
- Two ways
1. In aerobic conditions, re-oxidised via ETC
2. In anaerobic conditions, re-oxidised by reducing pyruvate to other products during fermentation
Fates of pyruvate
- In aerobic conditions, cells with active TCA cycle and electron transport chains can fully metabolize pyruvate
- In anaerobic conditions or when cells lack the ability to further utilise pyruvate, two primary fates of pyruvate are Lactate or Ethanol
Ethanol fermentation
- Results in the oxidation of NADH to NAD+
- NAD+ can then return to glycolysis and be reused
- Ethanol fermentation allows cells to recycle NAD +/NADH
- Baking and brewing
Lactate fermentation
- Results in the oxidation of NADH to NAD +
- Lactate fermentation provides a crucial means for hypoxic tissue (low oxygen) that cannot undergo respiration to recycle NAD +/NADH
- Note that the reaction is reversible,
- When [NADH] is high, favours forward reaction
- Skeletal muscle and lactic acid bacteria
Enzyme activity
a) how much substrate is consumed (or how much product is formed) by an enzyme,
b) over a known period of time
c) from a given sample or reaction volume
Specific activity:
an expression that relates the enzyme activity to the mass of protein present in a sample.