The input of energy in the form of the hydrolysis of ATP
to either ADP and Pi
or to adenosine monophosphate
(AMP) and pyrophosphate powers the synthesis of biological
molecules, including, as we have seen, carbohydrates
in photosynthesis, proteins, DNA, RNA, and fatty acids.
To delve into the role of ATP in biosynthesis in depth
is not possible in this brief article. Aspects of fatty acid
biosynthesis, however, reveal interesting principles of the
energetics of biosynthetic pathways.
Fatty acids are oxidized completely to CO2
by β-oxidation and the citric acid cycle. Acetyl CoA is the
end product of β-oxidation of fatty acids and is the source
of carbon for fatty acid biosynthesis. Yet, the pathways for
fatty acid degradation and synthesis are so very different
that they even occur within different compartments within
cells. Fatty acid synthesis takes place in the cytoplasm of
animal cells and in the plastids of plant cells, whereas β-
oxidation is located in mitochondria in both animal and
Often, the pathway for the synthesis of a compound
differs significantly from that for its degradation. Among
the reasons that the separation of synthetic and degradative
pathways evolved are energetics and regulation. The
oxidation of fatty acids to acetyl CoA is very exergonic.
It is not feasible on energetic grounds to make fatty acids
from acetyl CoA by reversing β-oxidation. Metabolism
of carbohydrates and fats is regulated in mammals by
a number of hormones, including insulin, glucagon, and
epinephrine (adrenaline). Having separate pathways for
the degradation and the biosynthesis makes it possible to
turn off one pathway while up-regulating another. For example,
glucagon and epinephrine selectively stimulate the
breakdown of fats and fatty acids, whereas insulin has the
opposite effect. The fine control of fatty acid metabolism
that has evolved would clearly not be possible without
the existence of separate pathways for biosynthesis and
is required for the synthesis of fatty acids. Yet,
when fatty acid synthesis is carried out in the presence of
, the fatty acid made is devoid of radioactivity.
ATP is used to add CO2
to a precursor, and in a
subsequent step in the pathway of fatty acid biosynthesis,
this same CO2
is released. This seemingly perplexing phenomenon
may readily be explained on an energetic basis.
Acetyl CoA is carboxylated by using bicarbonate as the
source of CO2
andATP hydrolysis as the source of energy:
|⇒ Equation 
||acetyl CoA + ATP + HCO3− ↔ malonyl CoA +ADP + Pi.
The enzyme that catalyzes this reaction, acetyl CoA carboxylase,
contains biotin, one of the B vitamins. Several
other vitamins, including niacin (part of NAD+
) and riboflavin (part of FAD), are essential players
The carboxylation of acetyl CoA without the hydrolysis
of ATP is energetically unfavorable. The exergonic
hydrolysis of ATP pulls the reaction toward malonyl CoA
synthesis. But why bother to carboxylate acetyl CoA?
All the carbon atoms in synthesized fatty acids are derived
from the acetyl group of acetyl CoA. In principle,
fatty acids could be made by condensation of acetyl units
and subsequent reduction. However, the condensation of
two acetyl CoA molecules is energetically unfavorable.
The release of CO2
as part of a reaction helps to drive a
reaction to completion. The oxidative decarboxylation reactions
of the citric acid cycle illustrate this fact. The loss
from the malonyl group as it condenses with the
acetyl group bound to the fatty acid synthetase drives the
condensation reaction. The resulting β-keto compound is
reduced to the level of a hydrocarbon by NADPH.
ATP hydrolysis provided the energy for the carboxylation
of acetyl CoA. The immediate energy source for
the condensation reaction was the loss of the same CO2
molecule added to the acetyl CoA. It is clear that CO2
a catalytic but essential role in fatty acid biosynthesis.