Pyruvate - Lactate

1
Pyruvate - Lactate

• Which one ends Glycolysis?

Glycolysis ends with the synthesis of pyruvate.
But, to be self-functioning, it must end with
lactate. Why? Anaerobic means without oxygen.
This is tantamount to saying without
mitochondria. The mitochondria are especially
adept at oxidizing NADH to NAD. NAD is needed
to keep the glyceraldehyde-3-PO4 dehydrogenase
reaction functioning. If glycolysis is to
continue when no oxygen is present or in short
supply (as in a working muscle), an alternative
means of oxidizing NADH must occur. This lesson
will show you how pyruvate is oxidized to
lactate. Using the same line of reasoning, you
will also see why yeast produce ethanol
2
By now you have seen the glycolysis pathway
begins with glucose and ends with pyruvate (click
1). Pyruvate has 2 metabolic fates it can
either be converted into lactate (click 1) or to
acetyl-CoA (click 1). Note that in animals and
plants the electrons in NADH are transferred to
pyruvate which reduces the carbonyl carbon in the
pyruvate molecule to an alcohol. The reaction is
catalyzed by the enzyme lactate dehydrogenase
(click 1). Lactate (or L-lactate to be more
precise) is thus a waste product, since it has
no metabolic fate other than to be converted back
into pyruvate in a reverse of the forward
reaction. More importantly, the NAD feeds back
to the glyceraldehyde-3-PO4 dehydrogenase
reaction, which allow glycolysis to continue.
Were it not for lactate formation, glycolysis as
a self-functioning pathway could not exist.
Click 1 to go on.
Glucose
Glucose-6-PO4
Pyruvate
Lactate
Acetyl-CoA
3
In yeast a slightly different end of glycolysis
becomes apparent. Yeast do not synthesize
lactate. They do, however, oxidize NADH back to
NAD anaerobically. How do they do this? The
answer is they make ethanol. In the reaction the
pyruvate is converted into acetaldehyde. The
reaction is catalyzed by a lyase enzyme, pyruvate
decarboxylase, which removes the carboxyl group
as a CO2 (click 1). You should note that
acetaldehyde is formed because the electron pair
that bonds the COO group is not removed by the
decarboxylation (click 1). A proton is plucked
from the environment giving the final product,
acetaldehyde (click 1). Acetaldehyde is now the
substrate that will oxidize NADH to NAD and in
the process ethanol is formed (click 1). Can you
name the enzyme that catalyzes this last
reaction? Try, it, then click 1 to see if you
picked the right one. Click 1 to go on.
H
Alcohol dehydrogenase
4
There is another advantage to the
pyruvate-lactate interchange. The reaction
catalyzed by lactate dehydrogenase is reversible.
This allows a cell to synthesize glucose from
lactate (click 1). Converting lactate to glucose
is a major feature of gluconeogenesis, an
anabolic pathway that synthesize glucose from
smaller precursors such as lactate. This is
important because acetyl-CoA cannot be converted
back to pyruvate and hence cannot be a source of
carbons for glucose biosynthesis (click 1).
Click 1 to go on.
5
What did you learn. Click to find the answer.
1. You have seen that NAD is recycled back by
oxidizing NADH. What other compound in the
glycolysis pathway must be recycled to keep the
pathway going. What reactions are connected for
this compound? Click 1 for answer.
ADP. ADP is required in the 3-phosphoglycerate
kinase reaction and in the pyruvate kinase
reaction. Its is formed from ATP in the
hexokinase reaction and the phosphofructokinase-I
reaction.
2. Yeast causes bread to rise (leaven) during
baking. Bread rises because a gas is released
during the baking. Name this gas and the reaction
that gives rise to it?
CO2. CO2 comes from the carboxyl groups of
organic acids. Pyruvate decarboxylase catalyzes
the decarboxylation of pyruvate releasing the
carboxyl group as CO2.
3. Your textbook (p 406) discusses the Pasteur
Effect and mentions that more glucose is
catabolized with O2 present than in its absence.
The Pasteur effect also pertains to an inhibition
of ethanol production by allowing O2 in during
fermentation (glycolysis). This in effect
devastated the French wine industry. In effect,
there is a competition between the glycolysis and
the mitochondria for limiting substrates and
coenzymes. What compounds are being competed
for that could hinder ethanol production?
NADH, ADP and PO4. This is a tough question,
but it gives you a little more insight into the
importance of NADH oxidation in glycolysis. NADH
is converted into NAD in the mitochondria. That
reaction is promoted by O2 NAD stays in the
mitochondria. Also in the mitochondria, ATP is
formed by condensing ADP with PO4. Thus, O2
allows mitochondria to out-compete the cytosol
for ADP, NADH and PO4, all limiting substrates or
coenzymes. This shuts off ethanol production and
turns wine into grape juice. As Louis Pasteur
would say, Sacre bleu (oh darn!).