induced hydrolysis of phosphatidylinositol
4,5-bisphosphate by phospholipase C to
produce inositol-1,4,5-trisphosphate and
diacylglycerols. In turn, the diacylglycerols
and the calcium mobilized by inositol
trisphosphate activate protein kinase C,
which has many diverse effects on cellular
growth and metabolism. Many hormones
and growth factors activate isoforms of
phospholipase C, including epinephrine and
norepinephrine, serotonin, thromboxane
A 2 , histamine, cholecystokinin, epidermal
growth factor, nerve growth factor and
platelet-derived growth factor (Exton,
1997).
During the last decade, phosphatidyl-
choline also has been found to participate
in cell signalling mechanisms, through
agonists that stimulate phospholipase D
activation. The products of this reaction
are choline and phosphatidic acid, which
may in itself serve as a signalling
mechanism as well as being converted
rapidly to diacylglycerol by phospha-
tidate phosphohydrolase. Phosphatidic
acid also may be converted by a specific
phospholipase A 2 to form lysophospha-
tidic acid, which is recognized as an
important intercellular messenger, parti-
cularly in stimulating growth. As dis-
cussed earlier, hydrolysis of arachidonic
acid from phosphatidylcholine by
phospholipase A 2 leads to formation of
the eicosanoids.
Recently, a new pathway of cell signal-
ling has been discovered that works
through sphingomyelin (Exton, 1997).
Activation of sphingomyelinase by
agonists such as tumour necrosis factor-,
interferon- and 1,25-dihydroxychole-
calciferol causes hydrolysis of sphingo-
myelin to produce ceramide and
phosphocholine. Ceramide is a potent
intracellular signalling factor that has
widespread effects on cellular growth,
differentiation and viability. Furthermore,
ceramide can be converted by removal of
its fatty acyl group to sphingosine, which
is an inhibitor of protein kinase C.
Sphingosine in turn can be phosphorylated
to form sphingosine-1-phosphate, which
has different cell signalling properties.
Progress in this exciting area is extremely
rapid (Eyster, 1998) and it is likely that
additional information on these pathways
in farm animals will be forthcoming.Future Perspectives
Although much is known about the basic
pathways of lipid metabolism and their
regulation in farm animals, the processes of
lipid accretion and lipid secretion in milk
will continue to assume great importance
in future research. This prominence is
stimulated by the tremendous impact that
lipid synthesis has on the efficiency, or
inefficiency, of meat and milk production.
In turn, this directly affects profitability of
livestock enterprises. Lipid metabolism
also plays a key role in development of
metabolic disorders such as fatty liver,
ketosis and pregnancy toxaemia, which
continue to plague livestock producers.
Supplemental fats are now standard
components of diets fed to high-producing
dairy cows, and are common in both swine
and beef diets. Continued efforts to
enhance the digestibility and utilization of
dietary fatty acids will improve the
energetic efficiency of milk and meat
production.
Increased understanding of lipid
metabolism should lead to practical
approaches to enhance the productivity
and health of farm animals. Various
biotechnological approaches to manipulate
the process of growth or milk production,
such as somatotropin, target key aspects of
lipid synthesis. Development of transgenic
livestock may be able to exploit desirable
pathways or overcome limitations in others
to alter lipid metabolism. Finally, unravel-
ling the roles and metabolism of the lipid-
derived cell signalling mechanisms will
have a huge impact on understanding the
cellular processes of growth in farm
animals, as well as on the cellular
mechanisms underlying homeostatic
actions of circulating hormones and growth
factors.116 J.K. Drackley