The Oxidation of Carbon Fuels Is an Important Source of Cellular Energy

II. Transducing and Storing Energy
14. Metabolism: Basic Concepts and Design
14.1. Metabolism Is Composed of Many Coupled, Interconnecting Reactions
Table 14.1. Standard free energies of hydrolysis of some phosphorylated compounds
Compound
Phosphoenolpyruvate
1,3-Bisphosphoglycerate
Creatine phosphate
ATP (to ADP)
Glucose 1-phosphate
Pyrophosphate
Glucose 6-phosphate
Glycerol 3-phosphate
II. Transducing and Storing Energy
14. Metabolism: Basic Concepts and Design
kcal mol- kJ mol1
1
-14.8
-11.8
-10.3
- 7.3
- 5.0
- 4.6
- 3.3
- 2.2
-61.9
-49.4
-43.1
-30.5
-20.9
-19.3
-13.8
- 9.2
14.1. Metabolism Is Composed of Many Coupled, Interconnecting Reactions
Figure 14.7. Sources of ATP During Exercise. In the initial seconds, exercise is powered by existing high phosphoryl
transfer compounds (ATP and creatine phosphate). Subsequently, the ATP must be regenerated by metabolic pathways.
II. Transducing and Storing Energy
14. Metabolism: Basic Concepts and Design
14.2. The Oxidation of Carbon Fuels Is an Important Source of Cellular Energy
ATP serves as the principal immediate donor of free energy in biological systems rather than as a long-term storage form
of free energy. In a typical cell, an ATP molecule is consumed within a minute of its formation. Although the total
quantity of ATP in the body is limited to approximately 100 g, the turnover of this small quantity of ATP is very high.
For example, a resting human being consumes about 40 kg of ATP in 24 hours. During strenuous exertion, the rate of
utilization of ATP may be as high as 0.5 kg/minute. For a 2-hour run, 60 kg (132 pounds) of ATP is utilized. Clearly, it
is vital to have mechanisms for regenerating ATP. Motion, active transport, signal amplification, and biosynthesis can
occur only if ATP is continually regenerated from ADP (Figure 14.8). The generation of ATP is one of the primary roles
of catabolism. The carbon in fuel molecules such as glucose and fats is oxidized to CO2, and the energy released is
used to regenerate ATP from ADP and Pi.
In aerobic organisms, the ultimate electron acceptor in the oxidation of carbon is O2 and the oxidation product is CO2.
Consequently, the more reduced a carbon is to begin with, the more exergonic its oxidation will be. Figure 14.9 shows
the ∆ G° of oxidation for one-carbon compounds.
Although fuel molecules are more complex (Figure 14.10) than the singlecarbon compounds depicted in Figure 14.9,
when a fuel is oxidized, the oxidation takes place one carbon at a time. The carbon oxidation energy is used in some
cases to create a compound with high phosphoryl transfer potential and in other cases to create an ion gradient. In either
case, the end point is the formation of ATP.
14.2.1. High Phosphoryl Transfer Potential Compounds Can Couple Carbon Oxidation
to ATP Synthesis
How is the energy released in the oxidation of a carbon compound converted into ATP? As an example, consider
glyceraldehyde 3-phosphate (shown in the margin), which is a metabolite of glucose formed in the oxidation of that
sugar. The C-1 carbon (shown in red) is a component of an aldehyde and is not in its most oxidized state. Oxidation of
the aldehyde to an acid will release energy.
However, the oxidation does not take place directly. Instead, the carbon oxidation generates an acyl phosphate, 1,3bisphosphoglycerate. The electrons released are captured by NAD+, which we will consider shortly.
For reasons similar to those discussed for ATP (Section 14.1.4), 1,3-bisphosphoglycerate has a high phosphoryl transfer
potential. Thus, the cleavage of 1,3-BPG can be coupled to the synthesis of ATP.
The energy of oxidation is initially trapped as a high-energy phosphate compound and then used to form ATP. The
oxidation energy of a carbon atom is transformed into phosphoryl transfer potential, first as 1,3-bisphosphoglycerate and
ultimately as ATP. We will consider these reactions in mechanistic detail in Section 16.1.5.
14.2.2. Ion Gradients Across Membranes Provide an Important Form of Cellular
Energy That Can Be Coupled to ATP Synthesis
The electrochemical potential of ion gradients across membranes, produced by the oxidation of fuel molecules or by
photosynthesis, ultimately powers the synthesis of most of the ATP in cells. In general, ion gradients are versa-tile means
of coupling thermodynamically unfavorable reactions to favorable ones. Indeed, in animals, proton gradients generated
by the oxidation of carbon fuels account for more than 90% of ATP generation (Figure 14.11). This process is called
oxidative phosphorylation (Chapter 18). ATP hydrolysis can then be used to form ion gradients of different types and
functions. The electrochemical potential of a Na+ gradient, for example, can be tapped to pump Ca2+ out of cells
(Section 13.4) or to transport nutrients such as sugars and amino acids into cells.
14.2.3. Stages in the Extraction of Energy from Foodstuffs
Let us take an overall view of the processes of energy conversion in higher organisms before considering them in detail
in subsequent chapters. Hans Krebs described three stages in the generation of energy from the oxidation of foodstuffs
(Figure 14.12).
In the first stage, large molecules in food are broken down into smaller units. Proteins are hydrolyzed to their 20 kinds
of constituent amino acids, polysaccharides are hydrolyzed to simple sugars such as glucose, and fats are hydrolyzed to
glycerol and fatty acids. This stage is strictly a preparation stage; no useful energy is captured in this phase.
In the second stage, these numerous small molecules are degraded to a few simple units that play a central role in
metabolism. In fact, most of them sugars, fatty acids, glycerol, and several amino acids are converted into the acetyl
unit of acetyl CoA (Section 14.3.1). Some ATP is generated in this stage, but the amount is small compared with that
obtained in the third stage.
In the third stage, ATP is produced from the complete oxidation of the acetyl unit of acetyl CoA. The third stage consists
of the citric acid cycle and oxidative phosphorylation, which are the final common pathways in the oxidation of fuel
molecules. Acetyl CoA brings acetyl units into the citric acid cycle [also called the tricarboxylic acid (TCA) cycle or
Krebs cycle], where they are completely oxidized to CO2. Four pairs of electrons are transferred (three to NAD+ and one
to FAD) for each acetyl group that is oxidized. Then, a proton gradient is generated as electrons flow from the reduced
forms of these carriers to O2, and this gradient is used to synthesize ATP.
II. Transducing and Storing Energy
14. Metabolism: Basic Concepts and Design
14.2. The Oxidation of Carbon Fuels Is an Important Source of Cellular Energy
Figure 14.8. ATP-ADP Cycle. This cycle is the fundamental mode of energy exchange in biological systems.
II. Transducing and Storing Energy
14. Metabolism: Basic Concepts and Design
14.2. The Oxidation of Carbon Fuels Is an Important Source of Cellular Energy
Figure 14.9. Free Energy of Oxidation of Single-Carbon Compounds.
II. Transducing and Storing Energy
14. Metabolism: Basic Concepts and Design
14.2. The Oxidation of Carbon Fuels Is an Important Source of Cellular Energy
Figure 14.10. Prominent Fuels. Fats are a more efficient fuel source than carbohydrates such as glucose because the
carbon in fats is more reduced.
II. Transducing and Storing Energy
14. Metabolism: Basic Concepts and Design
14.2. The Oxidation of Carbon Fuels Is an Important Source of Cellular Energy
Figure 14.11. Proton Gradients. The oxidation of fuels can power the formation of proton gradients. These proton
gradients can in turn drive the synthesis of ATP.