The Nonlinear Cysteine Redox Dynamics in the i-Space: A Proteoform-centric Theory of Redox Regulation
Redox Biology,
Год журнала:
2025,
Номер
81, С. 103523 - 103523
Опубликована: Фев. 5, 2025
The
post-translational
redox
regulation
of
protein
function
by
cysteine
oxidation
controls
diverse
biological
processes,
from
cell
division
to
death.
However,
most
current
site-centric
paradigms
fail
capture
the
nonlinear
and
emergent
nature
in
proteins
with
multiple
cysteines.
Here,
we
present
a
proteoform-centric
theory
grounded
i-space.
i-space
encapsulates
theoretical
landscape
all
possible
proteoforms.
Using
computational
approaches,
quantify
vast
size
abstract
i-space,
revealing
its
scale-free
architecture-elucidating
disproportionate
influence
cysteine-rich
proteins.
We
define
mathematical
rules
governing
proteoform
dynamics.
Their
dynamics
are
inherently
nonlinear,
context-dependent,
fundamentally
constrained
copy
numbers.
Monte
Carlo
simulations
human
PTP1B
reveal
extensive
sampling
beyond
models,
supporting
"oxiform
conjecture".
This
conjecture
posits
that
highly
oxidised
proteoforms,
molecules
bearing
cysteines,
central
regulation.
In
support,
even
90%-reduced
proteomes
can
house
numbers
unique,
potentially
functioanlly
diverse,
oxiforms.
framework
offers
transformative
lens
for
understanding
biology
Язык: Английский
Reactive Oxygen Species (ROS) in Metabolic Disease—Don’t Shoot the Metabolic Messenger
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(6), С. 2622 - 2622
Опубликована: Март 14, 2025
Reactive
oxygen
species
(ROS)
are
widely
considered
key
to
pathogenesis
in
chronic
metabolic
disease.
Consequently,
much
attention
is
rightly
focused
on
minimising
oxidative
damage.
However,
for
ROS
production
be
most
effectively
modulated,
it
crucial
first
appreciate
that
do
not
solely
function
as
pathological
mediators.
There
>90
gene
products
specifically
evolved
generate,
handle,
and
tightly
buffer
the
cellular
concentration
of
ROS.
Therefore,
likely
plays
a
role
integral
homeostatic
signalling
components
only
become
toxic
extremis.
This
review
explores
these
commonly
overlooked
normal
physiological
functions,
including
how
generated
response
environmental
or
hormonal
stimuli,
mechanisms
by
which
signals
propagated
regulated,
cell
brings
signal
an
end
after
appropriate
duration.
In
course
this,
several
specific
better-characterised
rely
upon
explored,
threshold
at
cross
from
beneficial
molecules
pathology
mediators
discussed.
Язык: Английский
Hydrogen Peroxide: A Ubiquitous Component of Beverages and Food
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(7), С. 3397 - 3397
Опубликована: Апрель 5, 2025
Hydrogen
peroxide
(H2O2)
plays
a
signaling
role
in
the
body.
Numerous
studies
demonstrated
that
H2O2,
generated
mainly
by
autoxidation
of
polyphenols,
ascorbate
and
other
reduced
compounds,
is
common
component
beverages
such
as
honey,
tea,
coffee,
formulated
drinks
alcoholic
beverages,
cooked
vegetables.
It
produced
fresh
milk
predominantly
xanthine
oxidase.
The
antimicrobial
action
honey
depends
on
H2O2
glucose
oxidase
polyphenol
autoxidation.
Many
components
food
scavenge
so
its
level
result
balance
between
generation
scavenging.
This
review
discusses
mechanisms
hydrogen
formation,
collects
evidence
for
presence
food,
fate
gastrointestinal
tract,
evolutionary
aspects
human
exposure
to
alimentary
peroxide,
both
adverse
possible
beneficial
effects
consumed
peroxide.
Язык: Английский