Energy Metabolism Part 8: What are the differences between aerobic and anaerobic metabolism?
Have you noticed that glycolysis, beta-oxidation, and the citric acid cycle are always referred
to as aerobic metabolic processes, although none of their reactions require oxygen?
In the last episode in this course on energy metabolism, we saw that just the last step
of the electron transport chain depends on oxygen.
Here, oxygen serves as the final electron acceptor for the reducing equivalents NADH
and H+ and FADH2.
Through electron transfer, oxygen is reduced to water at complex IV in the electron transport
chain.
Although just this reaction consumes oxygen, it has a decisive influence on the entire
energy metabolism: If the level of oxygen in a cell is insufficient, the electrons are
no longer able to leave the electron transport chain.
The protein complexes remain reduced and can’t pick up any more electrons from the reducing
equivalents.
This leads to excess NADH and H+ and FADH2, as well as a decrease in NAD+ and FAD.
The equilibrium shift to their reduced forms inhibits beta-oxidation, glycolysis, the pyruvate
dehydrogenase complex, and the citric acid cycle.
As a result, acetyl-CoA accumulates, which further enhances inhibition of the pyruvate
dehydrogenase complex.
When no aerobic metabolic processes are available to a cell, then how does it generate ATP?
One means is the conversion of two molecules of ADP to ATP and AMP via phosphate group
transfer.
In the mitochondrial intermembrane space, there’s even a dedicated enzyme for this
reaction, adenylate kinase.
In muscle cells, adenylate kinase provides energy for a short time.
Another means is the transfer of phosphate from creatine phosphate to ADP, yielding ATP
and creatine.
This phosphate transfer is catalysed by mitochondrial or cytosolic creatine kinase.
However, the most important source of ATP in oxygen deficiency is anaerobic glycolysis.
As for aerobic glycolysis, glucose is initially broken down to form pyruvate.
Though, pyruvate isn’t converted into acetyl-CoA and metabolized in the citric acid cycle:
It’s converted into lactate by the enzyme lactate dehydrogenase.
During lactate production, NADH and H+ is oxidized to NAD+.
This is how the process regenerates just enough reducing equivalents to maintain glycolysis.
Since lactate production occurs immediately after glycolysis, it’s sometimes referred
to as the eleventh reaction step of anaerobic glycolysis.
Yet, ATP production without oxygen has some disadvantages: The conversion of AMP back
to ATP is energetically unfavorable.
The creatine phosphate supply is very limited and can only be used for ATP synthesis for
a short period.
Finally, the anaerobic metabolism of pyruvate provides less than one-tenth of the amount
of energy produced by aerobic metabolism.
Anaerobic glycolysis yields only two ATP molecules per glucose, whereas aerobic glycolysis, the
citric acid cycle, and the electron transport chain yield a total of 32 molecules of ATP.
Another disadvantage of lactate production is that it lowers tissue pH.
But don't be misled: Lactate is indeed the anion of lactic acid and dissociates to lactate
and protons under physiological conditions.
Still, elevated lactate is most likely not the direct cause of the decrease in pH.
The acidic effect is usually attributed to proton cotransport processes triggered by
lactate transport.
To protect cells from damage, lactate dehydrogenase is inhibited by a low ambient pH value, limiting
the acidic effects.
Also, lactate is actively eliminated by the body.
If you’re interested in which processes play a role, then stay tuned for the next
episode of this course.
Despite the disadvantages described, the body needs to provide anaerobic energy.
Aerobic metabolism in muscles can’t start directly, even if the oxygen supply is adequate.
This initial period needs to be bridged by anaerobic processes.
In other words: the immediate energy supply in muscle cells is always anaerobic.
And of course, anaerobic processes are always required for gaining energy in the absence
of oxygen.
As the breakdown of carbohydrates and fats usually requires vast amounts of oxygen.
This quickly becomes evident when looking at the chemical equations of the breakdown
of glucose and palmitic acid: To convert one molecule of glucose into water and carbon
dioxide, six molecules of oxygen are required.
For the degradation of one molecule of palmitic acid, 23 molecules of oxygen are required.
This corresponds to one molecule of oxygen per carbon atom in glucose degradation and
around one-and-a-half molecules of oxygen per carbon atom for palmitic acid.
So, in particular, cells that aren’t directly supplied with oxygen by capillaries quickly
become oxygen deficient.
Looking at the whole body, aerobic and anaerobic metabolism always occur simultaneously, although
never in the same cell at once.
Physiologically, anaerobic energy production is also vital for cells operating beyond the
aerobic threshold or contributing to high-speed strength processes.
It’s also important for cells without mitochondria, such as erythrocytes.
These cells lack the cellular structures required for beta-oxidation or the citric acid cycle.
Lactate metabolism has important clinical implications:
As already mentioned, lactate production leads to a decrease in pH.
In severe cases, lactic acidosis can occur.
As a result, the serum pH drops below 7.35, while lactate levels increase above 4 mmol/L.
Lactic acidosis belongs to the metabolic acidosis group and requires urgent treatment.
Although it occurs rarely, it’s often fatal, as a pH below 7 is incompatible with life.
Potential causes of lactic acidosis are an inadequate oxygen supply, impaired lactate
clearance, or a generally disturbed metabolism.
Lactic acidosis is, for example, a potential complication of liver failure.
Some drugs can also cause lactic acidosis.
One such drug is metformin, which we introduced in episode 7 of this course.
As a reminder, metformin is a drug that’s used to lower blood glucose levels in the
treatment of type 2 diabetes mellitus.
It’s eliminated by the kidneys; so, in patients with severe renal failure, it may accumulate
in the body.
This accumulation enhances metformin's effect: Inhibition of complex I in the electron transport
chain leads to the inhibition of aerobic metabolism.
Instead, it promotes lactate metabolism and with this lactate production.
It's buildup can then lead to lactic acidosis.
With this, let's wrap up our comparison of anaerobic and aerobic metabolism and summarize
the most important points:
Aerobic metabolism requires oxygen to remove electrons from the electron transport chain.
Without oxygen, the reducing equivalents are no longer regenerated, leading to excess FADH2
and NADH and H+ and depletion of FAD and NAD+.
As a result, aerobic glycolysis, beta-oxidation, the citric acid cycle, and the pyruvate dehydrogenase
reaction are inhibited.
Adenylate kinase or creatine kinase reactions are a short-term source of energy if oxygen
levels are depleted.
Pyruvate is converted to lactate, thereby replenishing just enough NAD+ to be used to
continue producing pyruvate from glucose.
Anaerobic processes provide significantly less ATP than aerobic processes.
Anaerobic glycolysis yields only 2 molecules of ATP per glucose, compared to 32 ATP molecules
in aerobic glycolysis.
Anaerobic metabolic processes are further required to bridge the initial period of aerobic
processes, to provide energy to cells with depleted oxygen levels, as well as in cells
that don’t possess mitochondria, such as erythrocytes.
Now, if you’d like to test your knowledge on anaerobic glycolysis, stay put for the
quiz on the next slide.
Otherwise, the next episode of this course will continue with the Cori cycle.