Human Physiology, 14th edition (2016)

Cell Respiration and Metabolism 121

a greater rate of heat loss and less muscle mass (for shiver-
ing) than do adults. Small mammals such as mice retain large
amounts of brown fat into adulthood, but in adult humans the
brown fat is limited to the supraclavicular area of the ventral
neck. Although its distribution is limited, this brown fat is
believed to contribute to calorie expenditure and heat produc-
tion in adults (chapter 19, section 19.2).
Norepinephrine released by sympathetic nerves (chap-
ter 9) stimulates lipolysis within the brown adipose cell.

Figure 5.14 Beta-oxidation of a fatty acid. After the

attachment of coenzyme A to the carboxyl group ( step 1 ), a pair

of hydrogens is removed from the fatty acid and used to reduce

1 molecule of FAD ( step 2 ). When this electron pair is donated to

the cytochrome chain, 1.5 ATP are produced. The addition of a

hydroxyl group from water ( step 3 ), followed by the oxidation of

the b -carbon ( step 4 ), results in the production of 2.5 ATP from

the electron pair donated by NADH. The bond between the a

and b carbons in the fatty acid is broken ( step 5 ), releasing acetyl

coenzyme A and a fatty acid chain that is 2 carbons shorter than

the original. With the addition of a new coenzyme A to the shorter

fatty acid, the process begins again ( step 2 ). Acetyl CoA enters a

citric acid cycle and generates 1 ATP directly and 9 ATP from the

oxidative phosphorylation of 3 NADH and 1 FADH 2 obtained from

the cycle.

See the Test Your Quantitative Ability section of the Review

Activities at the end of this chapter.

H

C

OH

O

Fatty acid

βα

AMP + PPi

AT P

1.5 ATP

CoA

C

O

CoA

HH

Fatty acid C CC

O

CoA

FAD

FADH 2

Fatty acid C

H 2 O

O

C CoA

HO

H

2.5 ATP

NAD

NADH

Fatty acid C

O

Acetyl CoA

Citric

acid

cycle 10 ATP

CoA

1

2

3

4

5

+ H+

HH

CC

HH

Fatty acid

HH

CC

HH

C

H

H

C

O

C CoA

H

Fatty acid now

two carbons shorter

This releases long-chain fatty acids, which activate a unique

uncoupling protein called UCP1 located in the inner mito-

chondrial membrane. This transport protein uncouples

oxidative phosphorylation: it allows H^1 to move from the

intermembrane space into the matrix, thereby dissipating

the H^1 gradient needed to power the production of ATP by

ATP synthase (see fig. 5.9 ). The lower ATP concentrations

that result exert less inhibition of the electron transport

system, increasing the oxidation of fatty acids to generate

more heat.

Ketone Bodies

Even when a person is not losing weight, the triglycerides

in adipose tissue are continuously being broken down and

resynthesized. New triglycerides are produced while others

are hydrolyzed into glycerol and fatty acids. This turnover

ensures that the blood will normally contain a sufficient level

of fatty acids for aerobic respiration by skeletal muscles, the

liver, and other organs. When the rate of lipolysis exceeds the

rate of fatty acid utilization—as it may in starvation, dieting,

and in diabetes mellitus—the blood concentration of fatty

acids increases.

If the liver cells contain sufficient amounts of ATP so

that further production of ATP is not needed, some of the

acetyl CoA derived from fatty acids is channeled into an

alternate pathway. This pathway involves the conversion of

two molecules of acetyl CoA into four-carbon-long acidic

derivatives, acetoacetic acid and b -hydroxybutyric acid.

Together with acetone, which is a three-carbon-long deriva-

tive of acetoacetic acid, these products are known as ketone

bodies (see chapter 2, fig. 2.21). The three ketone bod-

ies are water-soluble molecules that circulate in the blood

plasma, and their production from fatty acids by the liver

is increased when there is increased lipolysis in the white

adipose tissue.