Download 17 The Citric Acid Cycle: The latabolism of Acetyl

The Citric Acid Cycle: The
latabolism of Acetyl-CoA
17
3fer A Mayes, PhD, DSc
TRODUCTION
Acetyl-CoA
(C2)
CoA
The citric acid cycle (Krebs cycle, tricarboxylic
d cycle) is a series of reactions in mitochondria that
ing about the catabolism of acetyl residues, liberat; hydrogen equivalents, which, upon oxidation,
ito the release of most of the free energy of tissue
Is. The acetyl residues are in the form of acetyli(CH3-CO~S-CoA, active acetate), an ester of
izyme A. Co A contains the vitamin panto thenic
Citrate
(C6)
Oxaloacetate
(C4)
MEDICAL IMPORTANCE
I The major function of the citric acid cycle is to act I
the final common pathway for the oxidation of carihydrate, lipids, and protein, since glucose, fatty Is,
and many amino acids are all metabolized to tylCoA or intermediates of the cycle. It also plays |major
role in gluconeogenesis, transamination, mination,
and lipogenesis. While several of these :esses are
carried out in most tissues, the liver is {only tissue in
which all occur. The repercussions |therefore
profound when, for example, large num-s of hepatic
cells are damaged or replaced by con-ctive tissue, as
in acute hepatitis and cirrhosis, re-j|vdy. A mute
testimony to the vital importance |citric acid cycle
is the fact that very few if any ; abnormalities of its
enzymes have been re-Jin humans; such
abnormalities are presumably latible with normal
development.
C02
CO2
Figure 1 7 - 1 . Citric acid cycle,
illustrating the catalytic role of oxaloacetate.
generated (Fig 17-1). Since only a small quantity of
oxaloacetate is needed to facilitate the conversion of a
large quantity of acetyl units to CC>2, oxaloacetate may
be considered to play a catalytic role.
The ckric acid cycle is the mechanism by which
much of the free energy liberated during the oxidation
of carbohydrate, lipids, and amino acids is made available. During the course of oxidation of acetyl-CoA in
the cycle, reducing equivalents in the form of hydrogen
or of electrons are formed as a result of the activity of
specific dehydrogenases. These reducing equivalents
then enter the respiratory chain, where large
amounts of ATP are generated in the process of oxidative phosphorylation (Fig 17-2; see also Chapter 13).
The enzymes of the citric acid cycle are located in
the mitochondrial matrix, either free or attached to
the inner surface of the inner mitochondrial membrane, which facilitates the transfer of reducing
equivalents to the adjacent enzymes of the respiratory chain, situated in the inner mitochondrial membrane.
BOLIC ROLE OF THE I
ACID CYCLE
mtially, the cycle comprises the combination of
ule of acetyl-CoA with the 4-carbon dicar-:
acid oxaloacetate, resulting in the formation on
tricarboxylic acid, citrate. There fol-[ series
of reactions in the course of which 2 pies of
C02 are released and oxaloacetate is re149