Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

54
Chapter | 3 Carbohydrate Metabolism and Its Diseases
FIGURE 3-9 Tricarboxylic acid cycle. The pathway for the entry of propionate into the metabolic scheme is
also included. The asterisks give the distribution of carbon in a single turn of the cycle starting with acetyl-CoA.
Note the randomization of carbon atoms at the succinate step.
by pyruvate carboxylase (PC). OAA formed by either route
may then be phosphorylated and decarboxylated to form
PEP in a reaction catalyzed by PEP carboxykinase (PEP-
CK). Thus, a pathway in the reverse direction of the PK
reaction is present for gluconeogenesis from lower intermediates.
These pathways for pyruvate metabolism are outlined
in Figure 3-8 , which includes the dicarboxylic acid cycle.
b . Tricarboxylic Acid Cycle
AcCoA formed by the oxidative decarboxylation of pyruvate
also has a number of metabolic routes available.
AcCoA occupies a central position in synthetic and in
oxidative pathways as shown in Figure 3-8 . The oxidative
pathway leading to the breakdown of AcCoA to CO 2 and
H 2 O follows a cyclical pathway that is the tricarboxylic
acid (TCA) cycle, citric acid cycle, or the Kreb’s cycle. The
major steps involved are given in Figure 3-9 . In a single
turn of the cycle, a mole of AcCoA enters, 2 moles of
CO 2 are evolved, and a mole of OAA is regenerated. The
regenerated OAA may then condense with another mole
of AcCoA, and the cycle continues. Citric acid is a symmetrical
molecule that behaves asymmetrically as shown
in Figure 3-9 . Also, the CO 2 that is evolved is derived from
that portion of the molecule contributed by OAA during
each turn of the cycle. The expected distribution of carbon
atoms from AcCoA in one turn of the cycle is also given in
Figure 3-9 . During one turn of the cycle, a randomization
of carbon atoms occurs at the succinate level such that CO 2
derived from the carboxyl group of acetate will be evolved
during the next turn of the cycle.
In the process, 3 moles of NAD and a mole of a flavin
nucleotide (FAD) are reduced, and a mole of ATP is
generated as noted in Figure 3-9 . In animal tissues, there
is a cytoplasmic NADP -linked isocitric dehydrogenase
(ICD), which is not associated with the mitochondrial
NAD -linked ICD or other enzymes of the TCA cycle.
The NADP -ICD is another enzyme used as an aid to
diagnose liver disease.