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12Lipoxygenases

**12-Lipoxygenases**

12-lipoxygenases (12-LOs) are a group of enzymes that catalyze the oxygenation of polyunsaturated fatty acids, particularly arachidonic acid, to form hydroperoxyeicosatetraenoic acids (HPETEs). These enzymes play a critical role in the biosynthesis of bioactive lipid mediators involved in inflammation, immune responses, and cellular signaling. There are three primary isoforms of 12-LOs, each with distinct tissue distribution and substrate specificity: 12-LO-1 (also known as 12-LO-1 or 15-LO-1), 12-LO-2 (12-LO-2 or 15-LO-2), and 12-LO-3 (12-LO-3 or 15-LO-3). The first two isoforms are found in mammals, while the third is present in plants and some invertebrates.

The primary substrate for 12-LOs is arachidonic acid, which is released from membrane phospholipids upon cellular

The biological functions of 12-LOs are diverse and context-dependent. In immune cells such as neutrophils and

activation.
The
enzymes
convert
arachidonic
acid
into
12(S)-HPETE,
which
is
further
reduced
to
12(S)-hydroxy-eicosatetraenoic
acid
(12-HETE).
12-HETE
is
a
potent
vasoconstrictor
and
chemotactic
factor
that
influences
leukocyte
migration,
vascular
permeability,
and
platelet
aggregation.
Additionally,
12-LOs
contribute
to
the
formation
of
leukotriene
B4
(LTB4)
through
a
secondary
pathway,
where
12-HETE
is
metabolized
by
other
enzymes.
macrophages,
12-LOs
are
involved
in
the
regulation
of
inflammation,
where
12-HETE
promotes
the
recruitment
of
inflammatory
cells
to
sites
of
injury
or
infection.
In
non-immune
cells,
such
as
endothelial
cells
and
fibroblasts,
12-LOs
may
contribute
to
processes
like
wound
healing,
fibrosis,
and
cancer
progression.
Dysregulation
of
12-LO
activity
has
been
associated
with
various
pathological
conditions,
including
asthma,
arthritis,
atherosclerosis,
and
certain
types
of
cancer,
making
them
potential
targets
for
therapeutic
intervention.
Research
into
12-LO
inhibitors
has
explored
their
potential
in
treating
inflammatory
diseases
and
other
disorders
linked
to
altered
lipid
mediator
signaling.