Human Physiology, 14th edition (2016)

Cell Respiration and Metabolism 109

atoms to pyruvic acid, which is thus reduced. This addition of

2 hydrogen atoms to pyruvic acid produces lactic acid ( fig. 5.4 ).

Most lactic acid dissociates to form the lactate anion and H^1 at

normal cellular pH (chapter 2; see fig. 2.12).

The metabolic pathway by which glucose is converted

into lactic acid is a type of anaerobic metabolism, in the

sense that the term anaerobic means that oxygen is not used

in the process. Many biologists prefer the name lactic acid

fermentation for this pathway because of its similarity to

the way that yeast cells ferment glucose into ethyl alcohol

(ethanol). In both lactic acid and ethanol production, the

last electron acceptor is an organic molecule. This contrasts

with aerobic respiration, in which the last electron acceptor

is an atom of oxygen. Biologists reserve the term anaerobic

respiration for pathways (in some microorganisms) that use

atoms other than oxygen (such as sulfur) as the last electron

acceptor. In this text, the terms lactic acid pathway, anaer-

obic metabolism, and lactic acid fermentation will be used

interchangeably to describe the pathway by which glucose is

converted into lactic acid.

The lactic acid pathway yields a net gain of two ATP

molecules (produced by glycolysis) per glucose molecule.

A cell can survive without oxygen as long as it can produce

sufficient energy for its needs in this way and as long as

lactic acid concentrations do not become excessive. Some

tissues are better adapted to anaerobic conditions than

others—skeletal muscles survive longer than cardiac muscle,

which in turn survives under anaerobic conditions longer

than the brain.

pathway consisting of nine separate steps. The individual steps
in this pathway are shown in figure 5.3.
In figure 5.3 , glucose is phosphorylated to glucose
6-phosphate using ATP at step 1, and then is converted into its
isomer, fructose 6-phosphate, in step 2. Another ATP is used
to form fructose 1,6-biphosphate at step 3. Notice that the
six-carbon-long molecule is split into 2 separate three-carbon-
long molecules at step 4. At step 5, two pairs of hydrogens
are removed and used to reduce 2 NAD to 2 NADH 1 H^1.
These reduced coenzymes are important products of glycoly-
sis. Then, at step 6, a phosphate group is removed from each
1,3-biphosphoglyceric acid, forming 2 ATP and 2 molecules
of 3-phosphoglyceric acid. Steps 7 and 8 are isomerizations.
Then, at step 9, the last phosphate group is removed from
each intermediate; this forms another 2 ATP (for a net gain of
2 ATP), and 2 molecules of pyruvic acid.

Lactic Acid Pathway

In order for glycolysis to continue, there must be adequate
amounts of NAD available to accept hydrogen atoms. There-
fore, the NADH produced in glycolysis must become oxidized
by donating its electrons to another molecule. (In aerobic res-
piration this other molecule is located in the mitochondria and
ultimately passes its electrons to oxygen.)
When oxygen is not available in sufficient amounts, the
NADH ( 1 H^1 ) produced in glycolysis is oxidized in the cyto-
plasm by donating its electrons to pyruvic acid. This results
in the re-formation of NAD and the addition of 2 hydrogen

Figure 5.2 The energy expenditure and gain in glycolysis. Notice that there is a “net profit” of 2 ATP and 2 NADH for every
molecule of glucose that enters the glycolytic pathway. Molecules listed by number are ( 1 ) fructose 1,6-biphosphate, ( 2 ) 1,3-biphosphoglyceric
acid, and ( 3 ) 3-phosphoglyceric acid (see fig. 5.3 ).

Glucose

Pyruvic acid

2 NADH

2 NAD

ADP

AT P

ADP

AT P

2 ATP

2 ADP + 2 Pi

2 ATP

2 ADP + 2 Pi

Free energy

1

2

3