Human Physiology, 14th edition (2016)

Cell Respiration and Metabolism 117

Cells cannot accumulate very many separate glucose molecules,
because an abundance of these would exert an osmotic pressure
(chapter 6) that would draw a dangerous amount of water into the
cells. Instead, many organs, particularly the liver, skeletal muscles,
and heart store carbohydrates in the form of glycogen.

Glycogenesis and Glycogenolysis

The formation of glycogen from glucose is called glycogenesis
( table 5.2 ). In this process, glucose is converted to glucose 6-
phosphate by utilizing the terminal phosphate group of ATP.
Glucose 6-phosphate is then converted into its isomer, glucose 1-
phosphate. Finally, the enzyme glycogen synthase removes these
phosphate groups as it polymerizes glucose to form glycogen.
The reverse reactions are similar. The enzyme glycogen
phosphorylase catalyzes the breakdown of glycogen to glucose
1-phosphate. (The phosphates are derived from inorganic phos-
phate, not from ATP, so glycogen breakdown does not require
metabolic energy.) Glucose 1-phosphate is then converted to
glucose 6-phosphate. The conversion of glycogen to glucose
6-phosphate is called glycogenolysis. In most tissues, glucose
6-phosphate can then be broken down for energy (through gly-
colysis) or used to resynthesize glycogen. Only in the liver, for
reasons that will now be explained, can the glucose 6- phosphate
also be used to produce free glucose for secretion into the blood.
As mentioned earlier, organic molecules with phosphate
groups cannot cross plasma membranes. Because the glucose
derived from glycogen is in the form of glucose 1-phosphate and
then glucose 6-phosphate, it cannot leak out of the cell. Simi-
larly, glucose that enters the cell from the blood is “trapped”
within the cell by conversion to glucose 6-phosphate. Skeletal
muscles, which have large amounts of glycogen, can generate
glucose 6-phosphate for their own glycolytic needs, but they
cannot secrete glucose into the blood because they lack the abil-
ity to remove the phosphate group.

Unlike skeletal muscles, the liver contains an enzyme—

known as glucose 6-phosphatase —that can remove the phosphate

groups and produce free glucose ( fig. 5.10 ). This free glucose can

then be transported through the plasma membrane. Thus, the liver

can secrete glucose into the blood, whereas skeletal muscles can-

not. Liver glycogen can thereby supply blood glucose for use by

other organs, including exercising skeletal muscles that may have

depleted much of their own stored glycogen during exercise.

5.3 INTERCONVERSION OF

GLUCOSE, LACTIC ACID, AND

GLYCOGEN

Glucose can be stored as glycogen. In the liver, stored gly-

cogen can be hydrolyzed and used to form free glucose,

which the liver can secrete into the blood. Lactic acid pro-

duced by exercising skeletal muscles can travel to the liver

and be converted into glucose.

LEARNING OUTCOMES

After studying this section, you should be able to:

4. Explain how glucose and glycogen can be inter-
   converted and why only the liver can use its stored
   glycogen to produce free glucose for secretion.


5. Define the term gluconeogenesis and explain the Cori
   cycle.

Term Process

Glycolysis Conversion of glucose into two molecules of

pyruvic acid

Glycogenesis The production of glycogen, mostly in

skeletal muscles and the liver

Glycogenolysis Hydrolysis (breakdown) of glycogen; yields

glucose 6-phosphate for glycolysis, or

(in the liver only) free glucose that can be

secreted into the blood

Gluconeogenesis The production of glucose from

noncarbohydrate molecules, including lactic

acid and amino acids, primarily in the liver

Lipogenesis The formation of triglycerides (fat), primarily

in adipose tissue

Lipolysis Hydrolysis (breakdown) of triglycerides,

primarily in adipose tissue

Ketogenesis The formation of ketone bodies, which are

four-carbon-long organic acids, from fatty

acids; occurs in the liver

Table 5.2 | Common Terms for Some

Metabolic Processes in the Body

Clinical Investigation CLUES

Andrea could eat a high-protein diet and still maintain a

normal blood glucose level.

• How does liver glycogen help maintain blood
  glucose?


• How does gluconeogenesis help maintain normal
  blood glucose?

Cori Cycle

In humans and other mammals, much of the lactic acid produced

in anaerobic metabolism is later eliminated by aerobic respira-

tion of the lactic acid to carbon dioxide and water. However,

some of the lactic acid produced by exercising skeletal muscles

is delivered by the blood to the liver. Within the liver cells under

these conditions, the enzyme lactic acid dehydrogenase (LDH)

converts lactic acid to pyruvic acid. This is the reverse of the

step of the lactic acid pathway shown in figure 5.4 , and in the

process NAD is reduced to NADH 1 H^1. Unlike most other