section 18.3
Metabolism of Ethanol
377
2
CH3c o s c o A -
Acetyl-CoA
A cety l-C o A
a c e ty ltr a n s fe ra s e
a
~
C H
3
C O C H
2
C O S C oA
C o A S H
^ A c eto a c e ty l-C o A
• CH
3
C O S C
0
A — ■
A cety l-C o A
H M G -C oA sy n th a s e *
*— »C oA S H
C H
3
i
O O C C H ,C C H ,C O S C o A
I
O H
ß -H y d ro x y -ß -m ethylglutaryl-C oA (H M G -C oA )
H M G -C oA ly a se
NADH + H
NAD
-CH
3
COSC
0
A + CH
3
COCH2COO
A c e to a c e ta te
cq-
CHjCOCH
A c e to n e
ß-H ydroxy-
b u ty ra te
d e h y d ro g e n a s e
-C H ,C H (O H )C H 2C O O
D -p-H ydroxy-
b u ty ra te
N o n e n zy m a tic
F IG U R E 1 8 -9
Ketogenesis in the liver. All reactions occur in mitochondria; the rate-controlling reactions (not shown) are release of
fatty acids from adipose tissue and uptake of acyl-CoA into mitochondria, in particular, the CPTI reaction (see
Figure 18-1). Acetoacetyl-CoA may regulate ketogenesis by inhibiting the transferase and the synthase.
*This enzyme is similar to citrate synthase (Chapter 13) which catalyzes an analogous reaction.
flow. D uring sustained exercise, the blood flow to the
liver, intestines, and kidneys is substantially decreased,
w ith a corresponding increase in b lood flow to w ork-
ing m uscles, so that m ore fatty acids m obilized from
adipose tissue are delivered to the m uscle. Thus, the
form ation o f ketone bodies is severely curtailed. But
during the postexercise period, w ith the resum ption o f
normal b lood flow to liver, ketone bodies are generated
as a result o f increased m obilization o f fatty acids. R e-
duced ketone body utilization in the extrahepatic tissues
can occur due to d eficiency o f either succinyl-C oA -
acetoacetate-C oA transferase or acetyl-C oA acetyltrans-
ferase. T h ese patients are susceptible to attacks o f ketoaci-
dosis and the presence o f persistent ketone bodies in the
urine.
18.3 Metabolism of Ethanol
Ethanol is consum ed w idely. M icrobial ferm entation in
the large intestine o f hum ans can produce about 3 g o f
ethanol per day. Ethanol is rapidly absorbed throughout the
gastrointestinal tract or, w hen inhaled, through the lungs.
It is m etabolized in the liver by a process having zero-
order kinetics; i.e., the rate o f oxidation is constant with
tim e. T he am ount m etabolized per unit tim e depends on
liver size (or body w eight); the average rate in an adult is
about 30 m L in 3 hours. The energy content o f alcohol is
about 7 kcal/g.
Ethanol oxidation begins w ith conversion to acetalde-
hyde by alcohol dehydrogenase (M .W . ~ 8 5 ,0 0 0 ), a zinc-
containing, N A D + -dependent en zym e that is a relatively
nonspecific cytoplasm ic en zym e w ith a
Km
o f about
1 m M /L :
C H
3
CH
2
O H + N A D + - * C H
3
CH O + N A D H + H+
A cetaldehyde is rapidly converted to acetate by N A D + -
dependent aldehyde dehydrogenase:
C H
3
CH O + N A D + + H 20 - »
C H
3
C O O H + N A D H + H+
Ethanol is also oxid ized by the m ixed-function oxid ase o f
sm ooth endoplasm ic reticulum , w hich requires N A D PH ,
oxygen , and a cytochrom e P -450 electron transport system
(Chapter 14):
C H
3
C H
2
O H + N A D P H + H + + 2 0
2
—
C H
3
CH O + 2H
2
0
2
+ N A D P+
M any drugs are m etabolized by this enzym e, hence
the com petition betw een ethanol and other drugs (e.g.,
