the TCA cycle. The succinyl-CoA is used to
add a succinyl group to a regulatory sub-
unit of HMG-CoA synthase, which
inactivates the enzyme.
In ruminants, CPT-I also is highly
sensitive to inhibition by methylmalonyl-
CoA (Brindle et al., 1985), which is an
intermediate in the conversion of
propionate to succinyl-CoA in the process
of gluconeogenesis. This may constitute an
additional adaptation of ruminants to link
the supply of energy-yielding compounds
from the diet with the need for hepatic
fatty acid oxidation. Furthermore, the
ability to distinguish between glucogenic
molecules originating primarily through
ruminal fermentation of dietary carbo-
hydrates (propionate) and those originating
from catabolism of endogenous amino
acids (e.g. pyruvate) has been proposed as
a unique adaptation of regulation of fatty
acid oxidation in ruminants during energy
deficit situations (Zammit, 1990).
Accelerated ketogenesis in response to
low blood glucose from insufficient dietary
energy intake may occur in both lactating
cows and pregnant ewes. The increased
ketogenesis is probably a factor of
increased mobilization of free fatty acids
from adipose tissue, increased uptake of
fatty acids by the liver, increased activity of
CPT-I, decreased sensitivity of CPT-I to
malonyl-CoA and increased activity of
HMG-CoA synthase.
Ketogenesis has been shown to occur at
lower rates in swine than in many other
species (Odle et al., 1995; Adams et al.,
1997). This may be due to limitations both
in the ability of swine to form acylcarnitines
for transport into the mitochondria (Odle et
al., 1995) and in the activity of HMG-CoA
synthase (Adams et al., 1997). Limitations
are particularly pronounced in neonates,
with some developmental increase in oxida-
tive capacity observed with advancing age
in pigs (Adams et al., 1997; Yu et al., 1997).
Peroxisomal metabolismAn alternate pathway for -oxidation in
liver is found in peroxisomes, which are
subcellular organelles present in most
tissues (Singh, 1997). The peroxisomal
pathway for -oxidation functions
similarly to the mitochondrial pathway,
with notable exceptions. First, the first
dehydrogenase step of mitochondrial -
oxidation is replaced with an oxidase step
(acyl-CoA oxidase) in the peroxisome,
resulting in formation of hydrogen
peroxide rather than reduced NAD+.
Second, peroxisomes do not contain an
electron transport chain. As a result of these
factors, peroxisomal -oxidation results in
capture of less energy as ATP than does
mitochondrial -oxidation. Another unique
aspect of the peroxisomal pathway is that
two enzymic activities of the -oxidation
pathway (enoyl-CoA hydratase and
3-hydroxyacyl-CoA dehydrogenase) are
performed by a single multifunctional
protein, called the bifunctional protein.
Peroxisomal -oxidation is active with
very long-chain fatty acids (20 carbons or
more) that are relatively poor substrates for
mitochondrial -oxidation. Because
peroxisomal -oxidation enzymes are
induced in rats by situations leading to
increased supply of fatty acids in the liver,
such as high dietary fat, starvation and
diabetes, the peroxisomal -oxidation path-
way has been discussed as an ‘overflow’
pathway to help cope with increased flux
of fatty acids (Singh, 1997).
Recent investigations in dairy cows
(Grum et al., 1994), sheep (Hansen et al.,
1995) and pigs (Yu et al., 1997) have
shown that the livers of these farm animals
possess relatively high peroxisomal -
oxidation activity. In neonatal pigs,
peroxisomal -oxidation increases rapidly
after birth in response to milk intake and
may be an adaptive mechanism to aid in
oxidation of long-chain fatty acids from
milk in the face of relatively low capacity
for mitochondrial fatty acid oxidation (Yu
et al., 1997). In dairy cows, peroxisomal
-oxidation is not induced by dietary fat
during lactation or by starvation (Grum et
al., 1994), but increases in response to
dietary fat and nutrient restriction during
the periparturient period. Subsequent to
the increased peroxisomal -oxidationLipid Metabolism 111