488
chapter
22
Metabolic Homeostasis
red-brown color. White adipocytes store triacylglycerol
for export as fatty acid to serve as fuel for other tis-
sues. In brown adipocytes, the lipid is oxidized within
the tissue to CO
2
and leads to the production of heat.
Brown adipocytes play a principal role in thermogenesis
(Chapter 14).
Human adipose tissue is mostly of the white type. It
responds rapidly to the supply of and demand for fuel
in the organism. Storage of fuel as triacylglycerol is ad-
vantageous over storage as glycogen, because triacylglyc-
erols are more highly reduced and release more energy per
gram when oxidized; in addition, lipids are stored anhy-
drously and therefore very compactly, whereas glycogen
must have an aqueous environment. As stored, triacylglyc-
erols yield four to five times more energy than do equiva-
lent amounts of glycogen. If the adipose tissue in the typi-
cal adult were replaced by an energy-equivalent amount of
glycogen, body weight would increase by 60% (from 70
to 115 kg). Adipocytes are highly active metabolically.
They synthesize triacylglycerols from glucose or from
fatty acids delivered by chylomicrons or very-low-density
lipoproteins (VLDLs). Glucose supplies acetyl-CoA for
the biosynthesis of fatty acids, the reducing power in the
form of NADPH produced by the pentose phosphate shunt,
and glycerol phosphate for esterification of fatty acids.
Glycerol phosphate is derived from intermediates of
glycolysis
because
adipocytes
lack
glycerol
kinase.
Adipocytes hydrolyze the triacylglycerol and release
fatty acids. Energy for adipocyte function is derived
primarily from fatty acid oxidation and TCA cycle
activity.
Skeletal Muscle
The typical adult has about 35 kg of skeletal muscle (see
also Chapter 21), which contains 5-6 kg of contractile
protein. Thus, skeletal muscle contains the major portion
of the body’s nonlipid fuels. In severe wasting diseases
or starvation, it can be depleted by about 40%. In the
well-fed state, it contains about
1
% of its wet weight as
glycogen. Because of its mass, muscle contains almost
four times as much glycogen as does the liver. Muscle
glycogen is not directly available as a source of blood
glucose because muscle lacks glucose-
6
-phosphatase, but
when mobilized to support muscular activity, glycogen
becomes available, via lactate for conversion into blood
glucose in the liver (discussed later). During starvation,
muscle protein provides amino acids, which become the
primary carbon source for maintenance of glucose home-
ostasis. Since there is no “storage” form of protein, the
protein that is degraded in muscle is the contractile pro-
tein. Resting muscle maintains itself mainly on energy
F I G U R E 2 2 -4
C o r i c y c l e .
Skeletal muscle anaerobic glycolysis yields lactate, which in
the liver is converted to glucose by gluconeogenesis, which provides more
glucose for support of muscle energy needs. The 2 mol of ATP generated
in muscle occurs at the expense of 6 mol of ATP in liver. Hepatic
metabolism is maintained by fatty acid oxidation. Muscle glycogen cannot
serve directly as a source of blood glucose because of the absence of
glucose-6-phosphatase.
provided by fatty acid oxidation. Muscle contraction can
be supported by anaerobic or aerobic glucose utilization
and by oxidation of fatty acids and amino acids, depend-
ing on the intensity of the exercise and the availability
of glucose and glycogen and of oxygen. The density of
mitochondria is lower in skeletal muscle than in heart or
liver, and severe exercise can result in the oxidative capac-
ity’s becoming insufficient. During anaerobic glycolysis,
2 mol of ATP is formed per mole of glucose whereas aer-
obic oxidation produces 34-36 mol. However, anaerobic
glycolysis permits muscle to function quickly at high in-
tensity in the absence of oxygen. The lactate produced
can be removed by the circulation and oxidized by the
heart or used by the liver for glucose homeostasis. Lactate
can be oxidized in muscle during rest following intense
exercise. The cyclic process of muscular anaerobic gly-
colysis maintained by hepatic gluconeogenesis is termed
the
Cori cycle
(Figure 22-4). This cycle is energetically ex-
pensive, since gluconeogenesis from lactate requires the
expenditure of
6
mol of ATP per mole of glucose formed
(Chapter 15). At rest, muscle can be a major contrib-
utor of amino acid carbon for gluconeogenesis. During
exercise it becomes the predominant user of metabolic
fuels.
Brain
The brain is a constant user of metabolic fuel, provided by
other tissues. It uses ~ 20% of the total oxygen consumed
by an adult in the resting state. Perhaps two-thirds of this
