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

X. Disorders of Ruminants Associated with Hypoglycemia
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oxidation rather than glucose plays the important role in
energy metabolism of the ruminant. Only about 10% of
the respiratory CO 2 arises from glucose oxidation, which
is considerably less than the 25% to 60% for the rat, dog,
and human. The glucose tolerance of the cow, however, is
the same as in other animals. The plasma clearance T 1/2
of 33 min in the cow is similar to that of dogs ( Kaneko
et al ., 1977 ) and humans.
About 60% of the glucose oxidized in the mammary
gland of the lactating cow occurs via the HMP pathway
( Fig. 3-6 ), the same as in the rat mammary gland. HMP
pathway activity in the ruminant mammary gland is also
evidenced by the high activities of the HMP enzymes,
G-6-PD and 6-P-GD, in sheep and cows mammary glands.
Thus, even though overall glucose utilization is lower in
ruminants, their pathways of glucose catabolism are the
same as in other animals. As in other animals, the HMP
pathway is the major provider of the reductive atmosphere
for the synthetic processes of the mammary gland.
Through the TCA cycle pathway, carbons from acetate,
from whatever source, appear in milk products ( Fig. 3-17 ).
Glucose carbon atoms may be given off as CO 2 , appear in
the amino acids of milk protein via transamination of oxaloacetate
and α -ketoglutarate, or appear in milk fat. The short
chain fatty acids of butterfat are synthesized from acetate in
the mammary gland, whereas the long chain acids of butterfat
are derived from blood lipids. The synthetic pathway for
fatty acids in the gland is the same as that in other animal
tissues (see Section IX).
The major portion of the glucose uptake by the mammary
gland provides for the biosynthesis of milk. The glucose
and galactose moieties of lactose are derived from
blood glucose. The rate of lactose synthesis is also constant
over a wide range of blood glucose concentrations of 1.1
to 4.4 mmol/l (20–80 mg/dl), which indicates that lactose
synthesis is maximal even under hypoglycemic conditions.
glucose
P.C.
NADPH
CO 2
E.M.
circulation
pyruvate
oxaloacetate
UDP- CO 2
galactose
a-ketoglutarate
lactose
CO 2
TCA
protein
MILK
acetate
citrate
CO 2
NADPH
ketone bodies
glycerol
fatty acid
FIGURE 3-17 Summary of some metabolic pathways in the mammary
gland.
fat
The mammary gland, therefore, is a glucose-utilizing tissue,
principally for biosynthesis and considerably less is
oxidized. The principal metabolic pathways involved are
summarized in Figure 3-17 .
Ruminant nervous tissue (i.e., brain) is also similar to
that of other animals in being an obligatory glucose-utilizing
tissue. The HK activity of sheep brain, however, is significantly
lower than that of rat brain. This means that even
though there is the same obligatory glucose requirement
between the ruminant and nonruminant, glucose utilization
by ruminant nervous tissue is lower than in the nonruminant.
Similarly, ruminant intestine and muscle use less glucose
than nonruminants.
With regard to organ distribution of gluconeogenic
enzymes, highest G-6-Pase activities are found in ruminant
livers as compared to other organs of ruminants and
are generally equal to or slightly lower than the activities
found in nonruminant livers. During early lactation,
the period when a cow’s glucose requirement is highest,
hepatic G-6-Pase does not increase. Similarly, cow liver
PEP-CK, a key gluconeogenic enzyme, is already very
high in comparison to that of rat liver. All of this is in
keeping with the concept that liver is primarily a glucose
producing tissue. This also means that the high producing
dairy cow that has been genetically selected for these
qualities is already synthesizing glucose maximally under
normal conditions. It follows that any additional demands
for glucose from physical stress, disease, and so on are
unlikely to be met by increased glucose production. This
glucose shortage leads to ketosis, the primary form from
excess milk production or secondary form from the stress
of a disease.
To summarize, the ruminant appears to be an animal
well adapted to a carbohydrate economy based on the
endogenous synthesis of glucose from noncarbohydrate
sources (gluconeogenesis). The enzymatic mechanisms for
gluconeogenesis are already operating at near maximal levels
in the high producing dairy cow. Glucose oxidation by
individual tissues as well as by the intact animal is lower
in ruminants than in nonruminants. Although overall partitioning
of glucose oxidation may be different in ruminants,
the pathways by which this oxidation is accomplished are
similar to those of other animals ( Fig. 3-17 ). The endocrine
relationships of ruminants are also qualitatively similar
to those of nonruminants so that the normally low blood
glucose concentrations of ruminants are a reflection of
their degree of influence or balance rather than their type
of action.
C . Biochemical Alterations in Body Fluids
1 . Hypoglycemia and Ketonemia
Hypoglycemia is such a consistent finding in bovine ketosis
and in ovine pregnancy toxemia that “ hypoglycemia ”