Cancer Res 2010:
. Synthesis of nucleic acids and nucleotides
is of utmost importance for proliferating tissues
and especially cancers.
. fructose's contribution to nucleic acid synthesis
is considerably greater than glucose;
and, cancer cells preferentially use fructose
via TKT-mediated metabolism
to synthesize additional nucleic acids
to facilitate increased proliferative capacity.
. previous studies have shown that
chronic fructose feeding in animals
leads to insulin resistance
and promotes in vivo growth,
as evidenced by increased organ weights
Additionally, in humans,
increased fructose consumption has been linked to
obesity, diabetes, and elevated uric acid levels,
the latter in keeping with our
in vitro metabolomic studies showing
increased fructose-directed nucleic acid synthesis
[ Metabolism. 1982, J Nutr. 1985].
We have recently shown 2.5-fold higher
serum fructose levels in pancreatic cancer patients
compared with healthy subjects;
furthermore, in healthy volunteers,
serum fructose level rose rapidly following
ingestion of a liquid fructose and glucose load,
and in contrast to glucose
that quickly returned to fasting levels,
serum fructose remained elevated for >2 hours,
suggesting that circulating human fructose levels
are unregulated in comparison with the
exquisite regulation of blood glucose [ Pancreas 2009 ].