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
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-3PO4 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
NADH + H+
COOC=O
Lactate
Pyruvate
Acetyl-CoA
CH3
Pyruvate
NAD+
COOHO-C-H
Lactate
CH3
dehydrogenase
L-lactate
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.
COO-
CO2
C=O
CH3 Pyruvate
Pyruvate
H
NADH + H+
NAD+
H
C=O
Alcohol
decarboxylase
dehydrogenase
Acetaldehyde
CH3
CH2OH
CH3
Ethanol
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.
Glucose
Lactate
Glucose-6-PO4
Pyruvate
Acetyl-CoA
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!).