25.
6 The Key Intermediate-AcetylCoA
Focus
Fatty acid metabolism and
carbohydrate metabolism
intersect at acetyl CoA.
Figure25.4
Themajorpathways of lipidmetab-
olismin the liverandtheirrelation-
shipto carbohydrate metabolism.
77t
tributes to energy production by entering glycolysis as dihydroxyacetone
phosphate.
25.6 Thekey intermediote-acetylCoA
AIMS: Toname the shoredintermedioteof both carbohydrote
ond fotty ocid metobolism,To list four fotes of ocetylCoA
in the liver.
Now that we have seen how the body oxidizes fatty acids, we can form an
overall picture of the various parts of fatty acid metabolism. We can exam-
ine the relationships between carbohydrate metabolism and fatty acid
metabolism at the same time. Since the liver conducts more carbohydrate
metabolism and fatty acid metabolism than any other organ, this discus-
sion will focus on it.
Figure 25.4 showsthe relationships we will be examining in the remain-
der of this chapter. Refer to it often as you read on. The figure shows that
774 25 Lipid Metabolism
CHAPTER

fatty acids entering the liver from the blood may be reslmthesizedinto
triglycerides and stored in the adipose tissue there. Alternatively, fatty acids
may be broken do',nmto aceryl CoA. Glucose is also broken do',nmto acetyl
CoA. If you are beginning to suspect that aceryl CoA must be a key com-
pound in the metabolic interplay between carbohydrate and fatty acid
metabolism, you are certainly correct. Four possible fates await the acetyl
CoA produced from fatty acids or glucose in the liver:
1. The acetyl CoA in the mitochondria may be oxidized to carbon dioxide
and water in the citric acid cycle and respiration. This pathway, which is
used if the liver cells need to generateenergy through respiration, makes
it clear that the citric acid cycle is shared by both glucose metabolism
and fatty acid metabolism.
2. The acetyl CoA in mitochondria may be used to synthesizethe sub-
stancescalled ketonebodies.Someketone bodies are oxidized for energy
production by the liver. The remainder are transpofted to other tissues
that can use them for energyproduction. Extensiveproduction of ketone
bodies from acetyl CoA occurs only when no glucose is available, as in
starvation or diabetes. When no glucose is available to starving brain
cells, for example, they adapt to the use of ketone bodies as an energy
sourcein about 48 hours.
3. The cltoplasmic acetyl CoA may be used to resynthesizefatty acids.
Since some of the acetyl CoA may have come from glucose,this means
that carbohydratesmay be converted to fatty acids.
4. The acetyl CoA may be used to slnthesize cholesterol in the cellular
cytoplasm. As with other synthetic processes,the slnthesis of fatty acids
and cholesterol occurs when the body is well supplied with energy.
Cells other than liver cells can carry out most of these four functions.
However, only the liver adds significant quantities of ketone bodies to the
bloodstreamfor transport to other tissues.

PRACTICE EXERCISE 25.5

\Mhat is the fate of acetyl CoA when the body needs energy?\Mhat is its
fate when energy needs are met?

25.7Fatty ocid synthesis

Converting carbohydrates to
fatty acids is an efficient way to
store energy.
AIM: To exploin the odvontogesof lipid energystoroge over
corbohydrateenergy storage. .1i
\-
canbe convertedto fats.The key.";$;;"i,hat
Carbohydrates
;!
links@.
bohydrate metabolism to fatty acid synthesisis acetyl CoA.lVhen body cells
have more glucose than they require to meet their energy needs, they can
divert some of the acetyl CoA produced by glucose catabolism to the syn-
thesis offatty acids.
Fatty acid synthesis and fatty acid oxidation are not the reverseof one
another, though both processesdo occur in cycles.In fatty acid slmthesis,a

o o
8CH3C-S-CoA + TATP + 14NADH ------CHS-eCHTJFC-OH
Acetyl CoA
The amount of energy that is re-
leasedupon complete oxidation of
a fuel can be measuredinabomb
calorimeter. Aweighed sample of a
fuel is burned in a closedchamber
situated in a water-filled, insulated
container. The heat given off is
calculated from the measured
increasein the temperature of the
knor,rmmass of water.
25.7 Fatty Acid Synthesis 775
two-carbon fragment is added to the growing fatty acid chain in each turn
of the cycle rather than being removed, as it is in fatty acid oxidation. More-
over, the synthesis and degradation of fatty acids involve different sets of
en4lmes. The cellular locations of the two processesare different as well:
Fatty acid synthesis occurs in the cytoplasm; fatty acid oxidation takes
place in the mitochondria. Like most slnthetic or anabolic pathways, the
slmthesis of fatty acids requires the expenditure of cellular reducing power
and ATP This requirement is clearly shorrrmby the overall equation for the
slnthesis of palmitic acid.
+ TADP + 14NAD+ + 8CoA + 6H2O + 7R
Palmitic acid
The newly synthesized fatty acids are incorporated into triglycerides and
are stored as depot fat in adipose tissues.
Lipids are a concentrated storageform of energy compared with carbo-
hydrates. There are two reasons for this. First, fatty acids are in a more
reduced state than carbohydrates;the carbon chains offatty acids are gen-
erally saturated hydrocarbons, whereasthe carbon chains of most carbohy-
drates are already partially oxidized to alcohols. Thus the bonds of fatty
acidshave more energyto releaseupon complete oxidation to carbon diox-
ide and water than the bonds of carbohydrates.This is why I g of fat
releases9 kcal of energy but I g of carbohydrate releasesonly 4 kcal. Sec-
ond, fats are stored in a nearly anhydrous, or dry state.In contrast, for each
gram of carbohydrate stored as glycogen, nearly 2 g of water is carried
along.
A reasonableamount of body fat is necessaryand beneficial, but main-
taining proper body weight is a problem for many people. From the meta-
bolic point of view dieting consists of reducing caloric intake so that stored
fats must be degraded to meet energy needs. Some people try to reduce by
eliminating all fatty foods from their diets. By eliminating foods that con-
tain fats, however, one runs the risk of also eliminating essential vitamins
and minerals contained in these foods. Moreover,if the decreasedfat intake
is more than compensated by an increased intake of carbohydrates-in
starchy foods, sweets, soda, and so forth-a person not only fails to lose
weight but actually gains.
Human beings convert carbohydratesto fats, but people do not convert
fats to carbohydrates. Human cells have no en4lrne that can catalyze the
conversion of acetyl CoA to pyruvate, a compound required for gluconeo-
genesis.Somebacteria, however,do have such an enzymq they convert fats
to carbohydrates as part of their normal metabolism.
PRACTICE EXERCISE 25-4
A person has a basalmetabolism of 1800Caloriesper day.Calculate(a)
the weight of fat that must be oxidized to CO2and H2O to provide this
amount of energy and (b) the weight of glucose that must be metabo-
lized to releasethis amount of energy.