Human Physiology, 14th edition (2016)

Cell Respiration and Metabolism 115

ATP Balance Sheet

Overview

There are two different methods of ATP formation in cell res-

piration. One method is the direct (also called substrate-level )

phosphorylation that occurs in glycolysis (producing a net

gain of 2 ATP) and the citric acid cycle (producing 1 ATP per

cycle). These numbers are certain and constant. In the second

method of ATP formation, oxidative phosphorylation, the

numbers of ATP molecules produced vary under different con-

ditions and for different kinds of cells. For many years, it was

believed that 1 NADH yielded 3 ATP and that 1 FADH 2 yielded

2 ATP by oxidative phosphorylation. This gave a grand total of

36 to 38 molecules of ATP per glucose through cell respiration

( table 5.1 ). Newer biochemical information, however, suggests

that these numbers may be overestimates, because, of the 36 to

38 ATP produced per glucose in the mitochondrion, only 30 to

32 ATP actually enter the cytoplasm of the cell.

Roughly 3 protons must pass through the respiratory assem-

blies and activate ATP synthase to produce 1 ATP. However, the

newly formed ATP is in the mitochondrial matrix and must be

continue. At the very last step of aerobic respiration, therefore,
oxygen becomes reduced by the 2 electrons that were passed
to the chain from NADH and FADH 2. This reduced oxygen
binds 2 protons, and a molecule of water is formed. Because
the oxygen atom is part of a molecule of oxygen gas (O 2 ), this
last reaction can be shown as follows:

O 2 1 4 e^2 1 4 H+ → 2 H 2 O

Figure 5.9 The steps of oxidative phosphorylation. ( 1 ) Molecules of the electron-transport system function to pump
H^1 from the matrix to the intermembrane space. ( 2 ) This results in a steep H^1 gradient between the intermembrane space and the
cytoplasm of the cell. ( 3 ) The diffusion of H^1 through ATP synthase results in the production of ATP.

First pump

Second

pump

Third

pump

NADH

2 H +^1 / 2 O 2

ADP

+

Pi H+

H+

H+

H+

e–

2 H+

4 H+

4 H+ NAD+

AT P

H 2 O

1

2

3

Outer mitochondrial

membrane

Inner mitochondrial

membrane

Intermembrane

space

AT P

synthase

1

Matrix

CLINICAL APPLICATION

Cyanide is a poison that binds to the enzyme cytochrome c

oxidase and inhibits the transfer of electrons from the fourth

respiratory complex to oxygen. This stops oxidative phos-

phorylation and deprives the cells of adequate amounts of

ATP. In smaller doses, cyanide may cause nausea, dizziness,

and headache; a greater exposure causes convulsions,

coma, and cessation of breathing, resulting in death. Cya-

nide is found in the pits of some fruits (such as apricots), and

in cigarette smoke. It is used in some manufacturing, and

has been used in poison gas.