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A random Abstract
Our Project
Our Team
Phenylalanine sensitive K562-D cells for the analysis of the biochemical impact of excess amino acid.
[phenylketonuria]
Although
it
is
recognized
that
the
abnormal
accumulation
of
amino
acid
is
a
cause
of
the
symptoms
in
metabolic
disease
such
as
phenylketonuria
(
PKU
)
,
the
relationship
between
disease
severity
and
serum
amino
acid
levels
is
not
well
understood
due
to
the
lack
of
experimental
model
.
Here
,
we
present
a
novel
in
vitro
cellular
model
using
K
562
-
D
cells
that
proliferate
slowly
in
the
presence
of
excessive
amount
of
phenylalanine
within
the
clinically
observed
range
,
but
not
phenylpyruvate
.
The
increased
expression
of
the
L-
type
amino
acid
transporter
(
LAT
2
)
and
its
adapter
protein
4
F
2
heavy
chain
appeared
to
be
responsible
for
the
higher
sensitivity
to
phenylalanine
in
K
562
-
D
cells
.
Supplementation
with
valine
over
phenylalanine
effectively
restored
cell
proliferation
,
although
other
amino
acids
did
not
improve
K
562
-
D
cell
proliferation
over
phenylalanine
.
Biochemical
analysis
revealed
mammalian
target
of
rapamycin
complex
(
mTORC
)
as
a
terminal
target
of
phenylalanine
in
K
562
-
D
cell
proliferation
,
and
supplementation
of
valine
restored
mTORC
1
activity
.
Our
results
show
that
K
562
-
D
cell
can
be
a
potent
tool
for
the
investigation
of
PKU
at
the
molecular
level
and
to
explore
new
therapeutic
approaches
to
the
disease
.
