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GLUCONEOGENESIS
Glucose
Gewese-6-phosphatase
Glucose-6-phosphate
12
Isomerase
Fructose-6-phosphate
X
Fructose-1,6-bisphosphatase
Fructose-6-bisphosphate
Glyceraldehyde-s-Phosphate
QUAD
S
↑
NAD+
&
witin
Glycerol-3-phosphate
DN
2
NAD
+4t
unit
Bisphosphoglycerate
Glycerol-3-phosphate
M
ADP
AD
A
Glycera
kinase
~
AT
3-phosphoglycerate
GLYCEROL
1
2-
Phosphoglycerate
e CYTOPLASM
Phasphdendpyruvate
~
ADP
GDP
AT
j
Pyrorate
LDH
LACTATE
PEPCK
GTP
L
ALT
ALANINE
Pyruvate
Pyruvate
MITOCHONDRIA
Carbaylase
v
Acetyl
con
occaloacetate
Nien)
MDH
NA1#
about
winge
even
the
synthesis of glucose from
non-carbohydrate
compounds
<partial
reversal
of
glycolysis)
lactate,
pyruvate,
fumarate,
glycerol,
propionate
Location-mainly
in
cytosol,
takes
place
mainly
in the
Liver
I
to some extentin
the
kidney
matrix.
Importance:
(a) Brain
CNS,
RBCs and
Testes are
dependant
on
glucose
for
continuous
supply
of
energy
(b)
Glucose
is
only
source
that
supplies energy
to skeletal muscle is anaerobic conditions
During fasting,
Gluconeogenesis
must
occur
to
meetbasal
requirements
of
glucose
for body.
Significance:
(a) Maintains
blood
glucose
during
stration.
13) Itis used to clear
the
waste
products
of
metabolism.
eg:
lactate
from
muscle
and
RBCs,
Glycerol
from adipose
tissue,
Propionyl
CoA
from
Boccidatich of
odd chain
fatty
acids.
These
compounds
are taken
up
by
liver-undergo
gluconeogenesis.
Regellatich:-
ENZYME INDUCER REPRESSOR ACTIVATOR INUIBITOR
Pyruvate
Carboxylase
Glucagon,
cortisal Insuli
Acetyl
CoA ADP
( (L
PEPCK
LI
1 Amp
Fructose I,
o
bisphosphatase
Citale Fructose
Bis-
11
12
phosphatase.
Glasses
phosphatase
GIYCOLYSIS
Heccokinase
Glucose
ATP
py
Glucose-6-Phosphate
Henokinase has a
low km
value,due to this
glucose
is utilised
by
he
kinase even at
low cone because
of
its
high
affinity
Energy
Gecokinase acts
only
at
higher
levels
of
glucose.
nvestment
Phase
Glucose-6-Phosphate
xIsomerase,
Fructose-6-Phosphate
Fructose-s-Phosphate
Phosphofaucoteinasl,
Fucfells
is a
bisphosphate
ATP Exp
This
step
is an irreversible committed and a
regulatory
step
Dihydroxyacetone
phosphate
Aldolase
~
Phosphotiose
se
Fructose-6-bisphosphatex
isomerase
Glyceraldehyde-3-Phosphate
Cycraldehyde-3-Phosphate
dehydrogenase
Glyceraldehyde-s-Phosphate
x
YI,3-Bisphosphoglycerate
NADt Art at
Lodoacetate
and
arsenate
inhibit
glyceraldehyde-3-phosphate
dehydrogenase
phosphoglycerate
kinase
I,3-Bisphosphoglyceratex
ADPL
3-Phosphoglycerate
again
ATP
Energy
Generatich
Pokinase reaction is reversible which
is rare
among
kinase reactions.
Phase
phosphoglycerate
3-phosphoglycerate
mutase;
2-Phosphoglycerate
ischerisation
reaction
I
Encase
(-Phosphoglycerate
Phosphonalpyruvate
U
Encase is inhibited
by fluoride,
during
blood
glucose
estimatic
floride
is added to
the blood to
prevent
slycolysis.
Prosphornalpyruvate
kinase,
Pyruvate
1
year
I
ADP ATP
Under Anaerobic conditions:
Glucose--->Pyruvate
lactate
dehydrogenase,
Lactate
NADH+H+
NADH
I
Icones
from
the
gets
utilised
again
reaction
catalysedby
~
glyceraldehyde-3-phosphate
dehydrogenase.
I
.
uninterrupted
glycolysis
in
skeletal
muscles
during
stenous
exercise.
Lactic
Acidosis.
Mildforms of
it
is associated with stenous
exercises,
shock, cancers,
etc.
· severe
forms
are observed due to
impairment/collapse
of
circulatory
sys
often
encountered
in
M.1,
pulmonary
embolism, severe shock.
Oxygen
Debt:
The excess amount
of
hygen
required
to recover.
of
ATP:
①under aerobic auditions
Step
(enzymes
source No.
of
ATP
formed
(a)
Hecoleinase
I ATP
(b)
Phosphofructokinase
Glyceraldehyde-3-phosphate dehydrogenase
NADPU
SATP
x
(d)
Phosphoglycerate
kinase ATP
2 AT
(e)
Pyruvate
Kinase
ATP
2
A T
Net
gain
=
TATP
② Under
Anaerobic
Conditions
Step
(enzymes
source No.
of
ATP
formed
(a)
Hecoleinase
I ATP
(b)
Phosphofructokinase
(d)
Phosphoglycerate
kinase ATP
2 AT
(e)
Pyruvate
Kinase ATP
2
A T
Net Gain=
ATP
RAPAPORT LEUBERING CYCLE
Glucose
i
Glyceraldehyde-3-phosphate
NADT
I
Glyceraldehyde-3-phosphate
NADH +H
y
dehydrogenase
1,3-Bisphosphoglycerate 2-Bromutase
2,3-Bisphosphoglycerate
3-phosphoglycerate
as-BPO
phosphatase
I
Pyruvate
Shunt
pathway)
NOTE:
supplementary
pathway
to
glycolysis
in
mature
RBCs
·
Production
of
2,3-BPO allows
glycolysis
to
proceed
without
synthesis
of
ATP.
· 2,3BPG combines
with ub
I
reduces its
affinity
towards
or,
... more
unloading
of
into
the
tissues.
↑
23BPG
in
RBCs is observed in
hypoxic
conditions,
high
altitudes,
eter
TCA
CYCLE
Pyruvate
NADt
pist
NADH
Ht
I
Baloacetate +
Acetyl
CA
veynthase,
citrates
Aconitase
Cis-Achitate
H20 Aconitase
Mox
Isociate
NAD+
"Isocitate
GTD
GDP
want want
went
not
dehydrogenase
Succings
(oA
Tartarated-keloglutarate
the
Qalosuccinate
Succinate
succinate
X
thiokinage
dehydrogenase
dehydrogenase
FAR
succinate
FAD dehydrogenase
NADF NADH +Ht
X
W
Fumarate Fumarase, L-Malatex
Daloacetate
malate
U
dehydrogenase
·
Primary
function
provision
of
energy
·
It has an
amphibolic
nature;
catabolic
role-final
common metabolic
pathway
for
acidation
of Acetyl
COAobtained
from
carbohydrates,
proteins
and
lipids
anabolic sale
from
intermediates
of
xA
cycle
several
compounds
can be
produced.
Regulation:
Regulatory Enzyme
Inducer
Repressor
Activator
Inhibitor
citate
synthase
Insulin
Glucagon
NADH,
ATP
Isocitate
dehydrogenase
Insulin
Glucagch
ADP, NADANADH,
ATP
-To
dehydrogenase
Insulin
Glucagon
ADP, NADt
NADU,
Al
When cel
requires
energy
cycle
runs
faster
and vice versa.
Aspartate
Gansaminases -
Aspartate
C-RTG
<
daloacetate
Glutamate.
Phosphonalcarboxy
kinase
unverts PEP to
Opaloacetate
GLYCOGENESIS
·
Formation
of
Glycogen
from
Glucose is
called
Glycogenesis
·
Site:-(a)
in cell=
cytosol
cb
tissue
Liver Skeletal Muscle
4%
cl.by
art. 0.2% wi.
by
cut
Total
content
Tog
240g
stored
⑧.
.
.
5-o-glycosidic
linkage
owse
molecule
·
Tywsidiceintage
Glycogen
·
Starting
Compound=
Glucose
End Product-
Glycogen
·
Reaction
Pathway:
(in
phases)
(a) Glucose
Reohinace/blucohinase,
Glucose-6-phosphate
hasphoghutal,
Guse
phasphate
X
ATP ADP
UDP Glucose
pyrophosphorylase
(UTP
PPi
UDP aluse=
donor
of
glu
ulse in
bywgen
synthesis
up
Gluset
......",
abcosyl
(b)
a
d
Transferase
Glycogenin
(protein)
bycogen
synthase
Glycogen
Primer
↓
⑧
uppa
p
.
&.
Branching
(Amylo
or
en
transferases
⑱
band
GLYCOGENOLYSIS
* Breakdown
of allogen
Tissue Site
Liver
Muscle
Intracellular
Site =
Cytesal
Starting
Material
=
Glycogen
End
Product: Glucose
in liver,
alwase-6-phosphate
in
muscles.
Reaction
Pathway.
olyerogen
is broken down
by
combined
actice
of benzymes
(a)
Glycogen Phosphorylase
Acts
on
glycogen-breaks
terminal cihbind-releases terminal
glucose
as
glucose-1-pon
Glycogen
glycogen
phosphorylase,
Glycogent
Gale
phosphate
(glucose
In (glucose)n -
Action
of
op occurs till-s
glucose
residues remain on either
sides
of
branch
point
(b) Glocan
Transferase
Transfers
3
glucose
residues
from
chain to
other thus
exposing
the C-1s branch
point
Debranching Enzyme-
splits
the
C-10 bond
at branch
point
I
releases
free glucose
90%
alvase-1-phosphat
After
removal
of
branch,
action
of
or continues.
10% Free Glucose.
... action
of
these 3
enzymes
complete
breakdown
of glycogen
to
give
⑧
⑧
⑧
⑧
one
~
o
-oooo
·
:
⑧
Glucan
⑧ mansgause
eme
* Fate
of Glucose-1-phosphate:
(a)
In Liver-
Glucose-I
phosphate
a
mutase,
base-sphosphate
Glucose-6-phosphate
gewuse-6-phosphatase,
Glasse
(b) In Muscle
muscles lack
glae-6-phosphatase
,
.. end
product-alvase-o-phelphale
muscle
glycogen->X
contribute to blood
glucose
Significance:
·
Hepatic
glycogenolysis
to maintain blood
glucose
level
· Muscle
glycogenolysis->provision of energy.
Regulatick:
Regulatory enzyme-Glycogen
Pherphorylase,
active
form
->
phosphorylated
form.
Activated
by
->
Glucagon
Adrenaline
Inhibited
by
-> Insulin
ATP ADP
1
kinase
Glycogen
Phosphorylase
Phosphatase
Glycogen
Phosphorylase
Cinactives (active)
HMP
SHUNT
PATHWAY
* Alternate
pathway
by
deidation
of geese.
I
of
glucose
enters
this
pathway
Tissue Site:
mainly
liver, RBC,
testis,
mammary
gland,
adrenal conten
Inkacellular site:
cytusal
starting
compound
Glucase-s-phosphate
* Reactich
pathway.
<phases
andalia are
e
(a)
Oscidative
Phase
Glucose-6-PPM
J-phosphoglucate
phosphoglahat
DM,
Ribulases-P
NADP
NADPH + at
NADP
NADPH + H+
Glucose-6-p is
sedatively
decarboxylated
to
ribulase-3- with NAB
production
(b) Non-Ocidative
Phase
Ribulose
-s-P
Ribulose -s-P Ribulose
-s-P
Epimerase
ischerase
eximerase
W
zo V
Xylolose-s-Pr
Ribose
Xylulose
7
1
Transketolase
[TPP,
Reg21)
~
Seddheptubre
TP -Glyceraldehyde
3P
Transaldolase
Fructose
6p
~
Erytrose
4P
↑
Ganstetolase
(TPP,
Mg2+)
2
Fructose 6P
~
Glyceroldeby
de 4P
(these then
enter
glycolysis
Significance
o
① Provision
of
NADPH which
is
required
for
synthesis
of
fatty
acids, retire bodies, molestral,
bile
acids/salls,
sterid
hor
ump
shunt-very
active
in
testis,
ovary,
adeenal
cortex
for phagocytosis
In
RBCs,
NADPH
protects
RBC
membrane
against
hemolysis
maintains
integrity
of
RBC
membrane.
NASA
required
maintain
availabilityof
reduced Glutathione.
RBC
has
a
che
of
Glutathiche
(reduced)
-> removes 1202
by
glutathione
peroxidase
enzyme
but
doing
so
gets
unverted to
oxidised
form-reduced
back
by
Glutathiche
reductase
enzyme
which
requires
NADPH
charmfull
creduced)
H202 2GSU
NADPt
Glutathiche Glutathione
peroxidase
reductase
H20-
~
GS-SG
NADPH +n+
<- Amp Shunt
caridised)
② Provision
of
Ribose-s-phosphate for
nucleotide
synthesis.
Clinical
Significance of
HMP
Shunt
Pathways
Glucose-6-phosphate
dehydrogenase deficiency
·
inherited X-linked
disorder,
most ammon
genetic
defect
in the world.
· does
not
exhibit
clinical
symptoms.
