>>Welcome to this segment of the Chemistry of Beer. The topic of this segment is anaerobic
metabolism. To begin our discussion of anaerobic metabolism, we will first of all think about
the big picture. Why must the cell not stop at pyruvate? This will require that we revisit
glycolosis. Next, we'll discuss the different fates of pyruvate when anaerobic conditions
prevail and then finally we'll wrap up some loose ends and summarize our discussion. To
begin our discussion of anaerobic metabolism, we first of all need to revisit glycolysis.
The step I wanted to emphasize was the step where NADH is formed. This is the gyceraldehyde
3-phosphate dehydrogenase reaction. We see that gyceraldehyde 3-phosphate is converted
to 1, 3-bisphosphoglycerate concurrent with that NAD+ is reduced to NADH. Remember this
happens twice, because we effectively have two glyceraldephyde 3-phosphates that are
converted to 1, 3-bisphosphoglycerate. So one of our products of glycolysis is two NADH
molecules. So I said earlier that the cell cannot stop at pyruvate. It has to do something
with that pyruvate. When aerobic conditions are prevailing, we've seen that the pyruvate
can enter the mitochondria and be oxidatively de-carboxylated to acetyl-CoA and then enter
the tricarboxylic acid cycle or the TCA cycle; but what happens when oxygen is limiting or
oxygen is not in great supply. How does the cell then function? If we look at our diagram
and we focus on pyruvate, the top part of our diagram, and we move to the left, that
would be what happens when oxygen is present. This can apply to both humans and yeast. When
oxygen is present, the pyruvate undergoes the reactions of the pyruvate dehydrogenase
complex where it is converted to acetyl-CoA, which can then enter the citric acid cycle.
The reduced cofactors FADH 2 and NADH can then enter the electron transport chain and
oxidative phosphorylation and we make a lot more ATP. As I mentioned earlier, oxidative
phosphorylation is much more efficient. But what happens when oxygen is not present or
not sufficient? In humans, the pyruvate will then undergo a reaction that's catalyzed by
the enzyme lactate dehydrogenase. This enzyme converts pyruvate into lactate. Specifically,
pyruvate is reduced to lactate. Therefore something else has to be oxidized. That something
else is NADH. NADH is oxidized back to NAD+. This is important because unless this happens
glycolysis cannot continue. There are limited pools of NADH and NAD+ and remember, glycolysis
forms NADH. If we don't somehow recycle and get back to NAD+ the cell can no longer run
glycolysis. So that is why in humans we have to do something with the pyruvate and that
something that we do is catalyzed by lactate dehydrogenase so that the pyruvate becomes
lactate and we regenerate NAD+. In yeast they have an enzyme which we don't have called
pyruvate decarboxylase. As the name implies, this enzyme catalyzes the decarboxylation
of pyruvate to make acetaldehyde. Acetaldehyde as you'll recall, is that toxic molecule and
so the yeast don't want that acetaldehyde levels to build up so the next reaction that
is catalyzed by our old friend ADH, alcohol dehydrogenase. This is the reverse of the
reaction that we learned when we discussed alcohol metabolism. Now the acetaldehyde is
being reduced to ethanol. This allows the NADH to be re-oxidized to NAD+ and that's
what the yeast needs in order to continue running glycolysis. It needs to regenerate
NAD+. So that is the secret to how yeast make ethanol. We grow them in conditions where
we deprive them of oxygen and that forces them to go anaerobic. They take the pyruvate,
which is the end product of glycolysis and they oxidatively decarboxylate it to acetaldehyde,
which they then reduce to ethanol, concurrent with the oxidation of NADH to NAD+. Now that
they've regenerated the NAD+ they can continue running glycolysis. So now we are ready to
wrap up our discussion of anaerobic metabolism. If the cell (yeast or human) is functioning
aerobically with oxygen, then the pyruvate can be further metabolized to carbon dioxide
and water via the pyruvate dehydrogenase complex, the tricarboxylic acid cycle, and the electron
transport chain and oxidative phosphorylation. This process yields significantly more ATP
than does the anaerobic process. If the cell (yeast or human) is functioning anaerobically,
then the pyruvate has to be reduced to lactate which happens in humans or decarboxylated
to acetaldehyde and then reduced to ethanol, which happens in yeast. Both of these pathways
regenerate NAD+, which is needed to continue running glycolysis.