Human Physiology, 14th edition (2016)

116 Chapter 5

1 FADH 2 and we get two citric acid cycles from 1 glucose, so

there are 2 FADH 2 that give 2 3 1.5 ATP 5 3 AT P.

The 23 ATP subtotal from oxidative phosphorylation we

have at this point includes only the NADH and FADH 2 produced

in the mitochondrion. Remember that glycolysis, which occurs

in the cytoplasm, also produces 2 NADH. These cytoplasmic

NADH cannot directly enter the mitochondrion, but there is a

process by which their electrons can be “shuttled” in. The net

effect of the most common shuttle is that a molecule of NADH

in the cytoplasm is translated into a molecule of FADH 2 in the

mitochondrion. The 2 NADH produced in glycolysis, therefore,

usually become 2 FADH 2 and yield 2 3 1.5 ATP 5 3 ATP by

oxidative phosphorylation. (An alternative pathway, where the

cytoplasmic NADH is transformed into mitochondrial NADH

and produces 2 3 2.5 ATP 5 5 ATP, is less common; however,

this is the dominant pathway in the liver and heart, which are

metabolically highly active.)

We now have a total of 26 ATP (or, less commonly,

28 ATP) produced by oxidative phosphorylation from glucose.

We can add the 2 ATP made by direct (substrate-level) phos-

phorylation in glycolysis and the 2 ATP made directly by the two

citric acid cycles to give a grand total of 30 ATP (or, less com-

monly, 32 ATP) produced by the aerobic respiration of glucose

(see table 5.1 ).

moved into the cytoplasm; this transport also uses the proton
gradient and costs 1 more proton. The ATP and H^1 are trans-
ported into the cytoplasm in exchange for ADP and P i , which
are transported into the mitochondrion. Thus, it effectively
takes 4 protons to produce 1 ATP that enters the cytoplasm.
To summarize: The theoretical ATP yield is 36 to 38 ATP
per glucose. The actual ATP yield, allowing for the costs of
transport into the cytoplasm, is about 30 to 32 ATP per glucose.
The details of how these numbers are obtained are described in
the following section.

Detailed Accounting

Each NADH formed in the mitochondrion donates 2 electrons
to the electron transport system at the first proton pump (see
fig. 5.9 ). The electrons are then passed to the second and third pro-
ton pumps, activating each of them in turn until the 2 electrons are
ultimately passed to oxygen. The first and second pumps transport
4 protons each, and the third pump transports 2 protons, for a total
of 10. Dividing 10 protons by the 4 it takes to produce an ATP (in
the cytoplasm) gives 2.5 ATP that are produced for every pair of
electrons donated by an NADH. (There is no such thing as half an
ATP; the decimal fraction simply indicates an average.)
Three molecules of NADH are formed with each citric
acid cycle, and 1 NADH is also produced when pyruvate is
converted into acetyl CoA (see fig. 5.5 ). Starting from 1 glu-
cose, two citric acid cycles (producing 6 NADH) and 2 pyru-
vates converted to acetyl CoA (producing 2 NADH) yield
8 NADH. Multiplying by 2.5 ATP per NADH gives 20 ATP.
Electrons from FADH 2 are donated later in the electron-
transport system than those donated by NADH; consequently,
these electrons activate only the second and third proton pumps.
Since the first proton pump is bypassed, the electrons passed from
FADH 2 result in the pumping of only 6 protons (4 by the second
pump and 2 by the third pump). Because 1 ATP is produced for
every 4 protons pumped, electrons derived from FADH 2 result in
the formation of 6 4 4 5 1.5 ATP. Each citric acid cycle produces

Phases of

Respiration

ATP Made

Directly

Reduced

Coenzymes

ATP Made by

Oxidative Phosphorylation

Theoretical Yield* Actual Yield**

Glucose to pyruvate (in

cytoplasm)

2 ATP (net gain) 2 NADH, but usually goes

into mitochondria as

2 FADH 2

If from FADH 2 :

2 ATP ( 3 2) 5 4 ATP

or if stays NADH:

3 ATP ( 3 2) 5 6 ATP

If from FADH 2 :

1.5 ATP ( 3 2) 5 3 ATP

or if stays NADH:

2.5 ATP ( 3 2) 5 5 ATP

Pyruvate to acetyl CoA ( 3 2) None 1 NADH ( 3 2) 5 2 NADH 3 ATP ( 3 2) 5 6 ATP 2.5 ATP ( 3 2) 5 5 ATP

Citric acid cycle ( 3 2) 1 ATP ( 3 2) 5 2 ATP 3 NADH ( 3 2) 5 6 NADH

1 FADH 2 ( 3 2) 5 2 FADH 2

3 ATP ( 3 6) 5 18 ATP

2 ATP ( 3 2) 5 4 ATP

2.5 ATP ( 3 6) 5 15 ATP

1.5 ATP ( 3 2) 5 3 ATP

Total ATP 4 ATP 32 (or 34) ATP 26 (or 28) ATP

• The theoretical yield is the number of ATP produced by oxidative phosphorylation inside the mitochondria.
  **The actual yield takes into account the energy cost of transporting ATP out of the mitochondria and into the cytoplasm.

Table 5.1 | ATP Yield per Glucose in Aerobic Respiration

| CHECKPOINT

2a. Compare the fate of pyruvate in aerobic and

anaerobic cell respiration.

2b. Draw a simplified citric acid cycle and indicate the

high-energy products.

3a. Explain how NADH and FADH 2 contribute to

oxidative phosphorylation.

3b. Explain how ATP is produced in oxidative

phosphorylation.