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

V. Interrelationships of Carbohydrate, Lipid, and Protein Metabolism
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3 . Carbon Dioxide Fixation in Animals
According to Figure 3-9 , the TCA cycle is a repetitive process
based on the regeneration of OAA at each turn. In
addition, other metabolic pathways are available for intermediates
in the cycle. Reversal of the transamination reactions
previously described to form aspartate or glutamate
would result in a withdrawal of OAA and α-KG, respectively,
from the cycle. By decarboxylation, OAA may also
be withdrawn to form PEP, and malate may form pyruvate
and thence other glycolytic intermediates as shown in Figure
3-8 . Continued losses of these intermediates into other metabolic
pathways would theoretically result in a decrease in
the rate of operation of the cycle. A number of metabolic
pathways are known whereby the losses of cycle intermediates
may be balanced by replacement from other sources
and are shown in Figure 3-8 . The amino acids, aspartate
and glutamate, may function as sources of supply as well as
routes for withdrawal. The CO 2 fixation reactions, which are
the reversal of the reactions previously described,
phosphoenolpyruvate CO oxaloacetate
pyruvate CO 2 →
2 → malate
pyruvate CO oxaloacetate
2 →
may also function as important sources of supply. A fourth
CO2-fixing reaction
propionate CO succinate
2
is especially important in ruminants because propionate is
a major product of rumen fermentation and is a major supplier
of intermediates for the TCA cycle. Propionate is one
of the three major fatty acids, with acetate and butyrate,
involved in ruminant metabolism.
4 . Energy Relationships in Carbohydrate Metabolism
The energy of carbohydrate breakdown must be converted
to high-energy phosphate compounds to be useful to the
organism; otherwise the energy is dissipated as heat. The
total available chemical energy in the reaction
glucose
→ 2 lactate
is about 50kcal/mole or about 7% of the 690kcal/mole,
which is available from the complete oxidation of glucose
to CO 2 and water. The useful energy of anaerobic glycolysis
is represented by the net gain of 2moles of ATP and
the available energy of each is about 7kcal. Thus, the efficiency
of glycolytic breakdown of glucose to pyruvate is
14kcal or 28% of the available 50kcal or only 2% of the
total available 690kcal in glucose.
The major portion of the energy of glucose is generated
in the further aerobic oxidation of pyruvate to CO 2 and
H 2 O. In the oxidative or dehydrogenation steps, NADH
or NADPH (FAD in the succinate step) is formed. In the
TABLE 3-3 ATP Yield in Glucose Oxidation
Glucose
presence of molecular O 2 , these compounds are reoxidized
to NAD or NADP in the cytochrome system. In the
sequence of reactions of this system, 3 moles of ATP are
formed per mole of NADH or NADPH oxidized to NAD
or NADP . This transfer of energy to ATP is known as
oxidative phosphorylation, or ox-phos. The yield of highenergy
phosphate bonds in the form of ATP in the system
per atom of oxygen consumed (½ O 2 ) is conventionally
referred to as the P:O ratio, which in this case is 3.
Table 3-3 presents a balance sheet of the ATPs formed
in the various steps, and 36 of the total 38 ATPs are generated
in aerobic glycolysis. The complete oxidation of
a mole of glucose to CO 2 and water yields 690kcal, and
therefore the net gain of 38 ATPs in anaerobic plus aerobic
glycolysis represents 266kcal for an overall efficiency of
38%. In comparison, the efficiency of the modern internal
combustion engine is about 20%.
V . INTERRELATIONSHIPS OF
CARBOHYDRATE, LIPID, AND
PROTEIN METABOLISM
ATP
| ATP (2X) 2
↓
fructose-1-6-diphosphate
| → NADH → 3 ATP (2X) 6
ATP (4X) 4
↓
2 pyruvate
NADH → 3 ATP (2X) 6
↓
2 acetyl-CoA
NADH → 3 ATP (6X) 18
ATP (2X) 2
FADH → 2 ATP (2X) 4
↓
4 CO 2
Net: Glucose → 6 CO 2
38 ATP
The pathways by which the breakdown products of lipids
and proteins enter the common metabolic pathway have
been described in previous sections. The principal points at
which carbohydrate carbon may be interconverted between
amino acids and fatty acids are outlined in Figure 3-10 .
Thus, certain amino acids (glycogenic) can serve as precursors
of carbohydrate through the transamination reactions,
and by reversal of these transaminations, carbohydrates can
serve as precursors of amino acids.