570
Chapter 16
Sources of Blood Glucose
The sources of blood glucose during the postabsorptive period
are as follows (see Figure 16–2):
1.
Glycogenolysis,
the hydrolysis of glycogen stores to
monomers of glucose-6-phosphate, occurs in the liver
and skeletal muscle. In the liver, glucose-6-phosphate
is enzymatically converted to glucose, which then
enters the blood. Hepatic glycogenolysis begins within
seconds of an appropriate stimulus, such as sympathetic
nervous system activation. Thus, it is the fi rst line of
defense in maintaining plasma glucose concentration.
The amount of glucose available from this source,
however, can supply the body’s needs for only several
hours before hepatic glycogen is nearly depleted.
Glycogenolysis also occurs in skeletal muscle,
which contains approximately the same amount of
glycogen as the liver. Unlike the liver, however, muscle
lacks the enzyme necessary to form glucose from the
glucose-6-phosphate formed during glycogenolysis.
Instead, the glucose-6-phosphate undergoes glycolysis
within muscle to yield ATP, pyruvate, and lactate. Some
of the lactate enters the blood, circulates to the liver,
and is converted into glucose, which can then leave the
liver cells to enter the blood. Thus, muscle glycogen
contributes to the blood glucose indirectly via the liver.
2.
The catabolism of triglycerides in adipose tissue yields
glycerol and fatty acids, a process termed
lipolysis.
The glycerol and fatty acids then enter the blood by
diffusion. The glycerol reaching the liver is converted to
glucose. Thus, an important source of glucose during
the postabsorptive period is the glycerol released when
adipose tissue triglyceride is broken down.
3.
A few hours into the postabsorptive period, protein
becomes another source of blood glucose. Large
quantities of protein in muscle and other tissues can be
catabolized without serious cellular malfunction. There
are, of course, limits to this process, and continued
protein loss during a prolonged fast ultimately means
functional disintegration, sickness, and death. Before this
point is reached, however, protein breakdown can supply
large quantities of amino acids. These amino acids enter
the blood and are taken up by the liver, where some can
be converted via the
α
-ketoacid pathway to glucose. This
glucose is then released into the blood.
Items 1 through 3 describe the synthesis by the liver of glu-
cose from pyruvate, lactate, glycerol, and amino acids. Synthesis
from any of these precursors is known as
gluconeogenesis
that is, “formation of new glucose.” During a 24-h fast, glu-
coneogenesis provides approximately 180 g of glucose. The
kidneys can also perform gluconeogenesis, but mainly during
a prolonged fast.
Glucose Sparing (Fat Utilization)
The 180 g of glucose per day produced by gluconeogenesis
in the liver (and kidneys) during fasting supplies 720 kcal of
energy. As described later in this chapter, normal total energy
expenditure for an average adult is 1500 to 3000 kcal/day.
Therefore, gluconeogenesis cannot supply all the energy needs
of the body. An adjustment must therefore take place during
the transition from the absorptive to the postabsorptive state:
Most organs and tissues, other than those of the nervous sys-
tem, markedly reduce their glucose catabolism and increase
their fat utilization, the latter becoming the major energy
source. This metabolic adjustment, termed
glucose sparing,
“spares” the glucose produced by the liver for the nervous
system’s use.
The essential step in this adjustment is lipolysis, the
catabolism of adipose tissue triglyceride, which liberates glyc-
erol and fatty acids into the blood. We described lipolysis in
the previous section in terms of its importance in providing
glycerol to the liver for conversion to glucose. Now, we focus
on the liberated fatty acids, which circulate bound to plasma
albumin. (Despite this binding to protein, they are known as
free fatty acids [FFA] because they are “free” of their attach-
ment to glycerol.) The circulating fatty acids are taken up and
metabolized by almost all tissues,
excluding the nervous system.
They provide energy in two ways (Chapter 3): (1) They fi rst
undergo beta oxidation to yield hydrogen atoms (that go on
to oxidative phosphorylation) and acetyl CoA; and (2) the
acetyl CoA enters the Krebs cycle and is catabolized to carbon
dioxide and water.
The liver is unique, however, in that most of the acetyl
CoA it forms from fatty acids during the postabsorptive state
does not enter the Krebs cycle but is processed into three com-
pounds collectively called
ketones,
or ketone bodies. (Note
that ketones are not the same as
α
-ketoacids, which, as we have
seen, are metabolites of amino acids.) Ketones are released
into the blood and provide an important energy source during
prolonged fasting for the many tissues,
including
those of the
nervous system, capable of oxidizing them via the Krebs cycle.
One of the ketones is acetone, some of which is exhaled and
accounts in part for the distinctive breath odor of individuals
undergoing prolonged fasting.
The net result of fatty acid and ketone utilization dur-
ing fasting is the provision of energy for the body while at the
same time sparing glucose for the brain and nervous system.
Moreover, as just emphasized, the brain can use ketones for
an energy source, and it does so increasingly as ketones build
up in the blood during the fi rst few days of a fast. The sur-
vival value of this phenomenon is signifi cant: When the brain
reduces its glucose requirement by utilizing ketones, much
less protein breakdown is required to supply amino acids for
gluconeogenesis. Consequently, the protein stores will last
longer, and the ability to withstand a long fast without serious
tissue damage is enhanced.
Table 16–2
summarizes the events of the postabsorp-
tive period. The combined effects of glycogenolysis, gluco-
neogenesis, and the switch to fat utilization are so effi
cient
that, after several days of complete fasting, the plasma glucose
concentration is reduced by only a few percent. After one
month, it is decreased by only 25 percent (although in very
thin persons, this happens much sooner).
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