The metabolism of the brain is remarkable in several respects. First, the brain of adult mammals normally uses only glucose as fuel (Fig. 22-8). Second, the brain has a very active respiratory metabolism; it uses almost 20% of the total O2 consumed by a resting human adult. The use of O2 by the brain is fairly constant in rate and does not change significantly during active thought or sleep. Because the brain contains very little glycogen, it is continuously dependent on incoming glucose from the blood. If the blood glucose should fall significantly below a certain critical level for even a short period of time, severe and sometimes irreversible changes in brain function may occur.
Although the brain cannot directly use free
fatty acids or lipids from the blood as fuels, it can,
when necessary, use D-β-hydroxybutyrate (a ketone body)
formed from fatty acids in hepatocytes. The capacity of
the brain to oxidize β-hydroxybutyrate via acetyl-CoA
becomes important during prolonged fasting or starvation,
after essentially all the liver glycogen has been
depleted, because it allows the brain to use body fat as
a source of energy. The use of β-hydroxybutyrate by the
brain during severe starvation also spares muscle
proteins, which become the ultimate source of glucose for
the brain (via gluconeogenesis) during severe starvation.
The concentration of glucose dissolved in the plasma
is also subject to tight regulation. We have noted the
requirement of the brain for glucose and the role of the
liver in maintaining the glucose concentration near the
normal level of 80 mg/100 mL of blood (about 4.5 mM).
When blood glucose in a human drops to half this value
(the hypoglycemic condition), the person experiences
discomfort and mental confusion (Fig. 22-10); further
reductions lead to coma, convulsions, and in extreme
hypoglycemia, death. Maintaining the normal concentration
of glucose in the blood is therefore a very high priority
of the organism, and a variety of regulatory mechanisms
have evolved to achieve that end. Among the most
important regulators of blood glucose are the hormones
insulin, glucagon, and epinephrine.
Lehninger-Nelson-Cox: Principles of Biochemistry, 744.o.
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