442
ERIC E. CONN
In Phase II the hexoses, fatty acids, glycerol, and amino acids are
converted to one of three compounds, acetyl-CoA, α-ketoglutarate, or
oxalacetate. In Phase III these three intermediates in turn are oxidized
to C0 2 and H 2 0 through the reactions of the tricarboxylic acid (Krebs)
cycle. In contrast to Phase I, the energy released in Phases II and III is
relatively large, and much of this energy is made available to the
organism.
Most of the energy available in foodstuffs is released when hydrogen
atoms are removed from oxidizable substrates, in turn reacting with 0 2
to form water. The over-all reaction is represented in highly simplified
form by Eq. 1.
Substrate + \ O2 —> Oxidized Substrate + H 2 0
(1)
The free energy changes (AF°) for oxidations encountered in Phases
II and III range from —35 to —70 kcal, per mole of substrate (I). In
many of the oxidation reactions, the immediate oxidizing agent is one
of the pyridine nucleotides,* DPN
+ or TPN
+ (Eq. 2).
Substrate + Oxidized pyridine nucleotide —> Oxidized substrate
+ Reduced pyridine nucleotide (2)
Thus in the glycolytic sequence reduced pyridine nucleotides are formed
when glyceraldehyde-3-phosphate, lactate, and pyruvate are oxidized.
The oxidation of glycerol and thioesters of ß-hydroxy fatty acids leads to
DPNH formation, and DPNH or TPNH is produced as a result of the
oxidation of malate, isocitrate, and α-ketoglutarate in the Krebs cycle.
The oxidative deamination of glutamic acid yields DPNH or TPNH.
In some instances the oxidizing agent is a flavoprotein instead of a
pyridine nucleotide (Eq. 3).
Substrate + Oxidized flavoprotein —> Oxidized substrate + Reduced flavoprotein (3)
The oxidation of succinate, the thioesters of fatty acids and the oxidative deamination of amino acids are examples of reactions in which
flavoproteins participate.
The free energy changes in reactions of the type shown in Eqs. 2 and
3 are usually not large; they may range from —10 to +10 kcal. These
values follow from a comparison of the oxidation-reduction potentials
of the various substrates with those for the pyridine nucleotides and
flavoproteins. Instead the large release of energy described in Eq. 1
occurs when the reduced coenzymes are reoxidized by molecular 0 2 .
* ABBREVIATIONS: DPN+ and DPNH, TPN+ and TPNH, oxidized and reduced
forms of di- and triphosphopyridine nucleotide; GSSG and GSH, oxidized and reduced glutathione; FAD, flavin adenine dinucleotide; AA, ascorbic acid; DHA, dehydroascorbic acid; AMP, ADP, and ATP, adenosine mono-, di-, and triphosphate;
P i? inorganic phosphate; DNP, dinitrophenol; CoA, coenzyme A.
ERIC E. CONN
In Phase II the hexoses, fatty acids, glycerol, and amino acids are
converted to one of three compounds, acetyl-CoA, α-ketoglutarate, or
oxalacetate. In Phase III these three intermediates in turn are oxidized
to C0 2 and H 2 0 through the reactions of the tricarboxylic acid (Krebs)
cycle. In contrast to Phase I, the energy released in Phases II and III is
relatively large, and much of this energy is made available to the
organism.
Most of the energy available in foodstuffs is released when hydrogen
atoms are removed from oxidizable substrates, in turn reacting with 0 2
to form water. The over-all reaction is represented in highly simplified
form by Eq. 1.
Substrate + \ O2 —> Oxidized Substrate + H 2 0
(1)
The free energy changes (AF°) for oxidations encountered in Phases
II and III range from —35 to —70 kcal, per mole of substrate (I). In
many of the oxidation reactions, the immediate oxidizing agent is one
of the pyridine nucleotides,* DPN
+ or TPN
+ (Eq. 2).
Substrate + Oxidized pyridine nucleotide —> Oxidized substrate
+ Reduced pyridine nucleotide (2)
Thus in the glycolytic sequence reduced pyridine nucleotides are formed
when glyceraldehyde-3-phosphate, lactate, and pyruvate are oxidized.
The oxidation of glycerol and thioesters of ß-hydroxy fatty acids leads to
DPNH formation, and DPNH or TPNH is produced as a result of the
oxidation of malate, isocitrate, and α-ketoglutarate in the Krebs cycle.
The oxidative deamination of glutamic acid yields DPNH or TPNH.
In some instances the oxidizing agent is a flavoprotein instead of a
pyridine nucleotide (Eq. 3).
Substrate + Oxidized flavoprotein —> Oxidized substrate + Reduced flavoprotein (3)
The oxidation of succinate, the thioesters of fatty acids and the oxidative deamination of amino acids are examples of reactions in which
flavoproteins participate.
The free energy changes in reactions of the type shown in Eqs. 2 and
3 are usually not large; they may range from —10 to +10 kcal. These
values follow from a comparison of the oxidation-reduction potentials
of the various substrates with those for the pyridine nucleotides and
flavoproteins. Instead the large release of energy described in Eq. 1
occurs when the reduced coenzymes are reoxidized by molecular 0 2 .
* ABBREVIATIONS: DPN+ and DPNH, TPN+ and TPNH, oxidized and reduced
forms of di- and triphosphopyridine nucleotide; GSSG and GSH, oxidized and reduced glutathione; FAD, flavin adenine dinucleotide; AA, ascorbic acid; DHA, dehydroascorbic acid; AMP, ADP, and ATP, adenosine mono-, di-, and triphosphate;
P i? inorganic phosphate; DNP, dinitrophenol; CoA, coenzyme A.