Anaerobic fates of pyruvate Flashcards
What happens when there is a lack of oxygen for respiration?
We need an alternative pathway for when there is no oxygen
Without O2, oxidative phosporylation cannot occur therefore depletes NAD+ and glycolysis stops
Humans - use homolactic fermentation (in muscles, to form lactate)
Yeast (microbial organisms)- use alcoholic fermentation (forming CO2 and ethanol)
In homolactic fermentation what reaction takes place?
Pyruvate + NADH ⇌ Lactate + NAD
Using lactate dehydrogenase (LDH)
NAD is regenerated in order to maintain flux through glycolysis
When ATP demand drops, lactate can be converted back to pyruvate for entry to the citric acid cycle
What is the LDH mechanism?
A hydride is transferred from C4 of NADH to C2 of pyruvate, accompaning a hydrogen atom transfer from His-195
His 195 and Arg 171 interact electrostatically with the pyruvate to orient it for catalysis in the active site
This is a stereo-specific reaction, the relative orientation of pyruvate and NADH means that it is always a specific hydride transferred from NADH
What is the overall reaction for glycolysis in the muscles undertaking anaerobic respiration?
Glucose + 2 ADP + 2 Pi ® 2 lactate + 2 ATP + 2H2O + 2H+
What is significant about lactate?
Lactate is the end, either converted ack to pyruvate or transported to the liver and used to synthesise glucose
It is not lactate in muscles that cause fatigue but rather a drop in pH (due to increase in H+)
What is the differenciation between the fibres used in respiration?
Slow twitch fibres - used for slow and steady contraction, aerobic respiration
Appear dark due to presence of chromosomes
Fast twitch fibres - used for fast bursts of energy, anaerobic respiration
Appear white as certain proteins aren’t needed for anaerobic respiration
What takes place within alcohol fermentation?
Pyruvate is converted into ethanol and CO2
This alcohol can be generated for brewing and more recently biofuels.
Release of CO2 is a rising agent for bread
What are the reactions that take place within alcohol fermentation?
- Pyruvate is converted into acetaldehyde, using pyruavte decarboxylase and releasing CO2
- Acetaldehyde + NADH is converted into ethanol + NAD, using alcohol dehydrogenase
Describe pyruvate decarboxylase?
Highly unstable and requires an ‘electron sink’
Not present in animals
Uses TPP as a cofactor - which is bound tightly but not covalently (it’s functional group is a thiazolium ring)
Describe the mechanism of pyruvate decarboxylase?
- Nucleophilic attack by ylid
- CO2 elimination - forms a resonance stabilised carbanion (here the thiazolium ring acts as an electron sink)
- Protonation of carbanion - to give hydroxyethylthiamine pyrophosphate
- TPP is eliminated to release acetaldehyde and regenerate the enzyme
As thiamine (vitamin B1) is essential in TPP cofactor, what is the effect of a deficiency?
Beriberi - thiamine deficiency
This leads to pain, paralysis and atrophy due to neurological disturbances
Therefore we now enrich our foods to avoid this issue
Wernicke-Korsakoff syndrome: characterised by dementia, ataxia and atrophy of the brain
Descrive alcohol dehydrogenase?
It is a metalloenzyme tetramer
It has an active site containing a catalytic zinc ion
How does alcohol dehydrogenase work?
The positive charge on the Zn2+ polarises the carbonyl group of acetaldehyde stabilising negative charge developing in transition state
Allows stereospecific transfer of hydrogen from NADH to acetaldehyde to form ethanol
What are the energetics of alcohol fermentation?
It is energetically favourable
Glucose -> 2 lactate + 2H+ ∆G = -196 kJ/mol
Glucose -> 2CO2 + 2ethanol ∆G = -235 kJ/mol
Homolactic fermentation is 31% efficient
Alcoholic fermentation is 26% efficient
What is the pasteur effect?
Far more sugar needs to be consumed anaerobically
As 2 ATPs are produced per glucose anaerobically compared to 32 ATPs produced per glucose under oxidative phosphorylation
