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1 Glucose 2 Pyruvate
Acetyl CoA
1. molecular oxygen
2. mitochonfrial enzymes
- pyruvate dehydrogenase complex
- citric acid
- respiratory chain
2
Phases of Glycolsis:
3 MAIN STA
Conversion of gluc
Overall Equation:
Glucose + 2 ADP + 2Pi 2 Lactate + 2 ATP + 2 H20
Has two types: Aerobic (in presence of oxidation) and
Anaerobic (e.g. erythrocytes)
Anaerobic glycolysis
- erythocytes do not have mitochondria;
they metabolize glucose thru the
anaerobic pathway
allows skeletal muscles to perform at
very high levels when oxygen supply
is inefficient, and it allows tissues to
survive anoxic episodes
glycogen disappears and lactate
appears
limits the amount of ATP formed per
mole of glucose oxidized. Therefore,
more glucose must be metabolized
when oxygen is admitted, aerobic
recovery takes place and lactate
disappears
erythrocytes
metabolize
glucose
anaerobically as they do not have
mitochondria
Anaerobic Degradation of Glucose to
Lactate
-forms lactic acid or lactate
-6-Carbon Glucose will yield 2
D-Glu
2 Pyruvate
2 Lactate
3.
PYRUVATE
AEROBIC- CO2 + H2O through Citric Cycle
and Electron Transport Chain
ANAEROBIC- lactic acid or ethanol
- less energy is generated
Lactic Acid - in skeletal muscle, when
energy needs outspace the ability to
transport oxygen
Why use Fermentation/Anaerobic?
REACTIONS OF GLYCOLYSIS
STEP 1 (IRREVERSIBLE)
Glucose + ATP glucose 6-phosphate + ADP + H
Glucokinase
only in liver
20 mmol/L
high
low
Specificity
acts on:
glucose;fructose
Induction
not induced
Function
glucose is utilized
by cells even if
blood sugar level is
low
Acts on:
mannose;
glucose
induced by
insulin and
glucose
acts only
when blood
glucose level
is more
than
100mg/dl;glu
cose then is
taken up by
liver cells for
glycogen
synthesis
STEP 2 (REVERSIBLE)
specific for glucose 6-phosphate and fructose 6PO4
STEP 5
Dihydroxyacetone phosphate (DHAP)
glyceraldehyde 3-phosphate (G3P)
Enzyme
TPI
(TRIOSE
PHOSPHATE
ISOMERASE) is the enzyme that allows the
conversion of DHAP to G3P.
G3P proceeds on the direct pathway of
glycolysis, DHAP does NOT. But TPI is there
to
convert
DHAP
to
G3P
through
ISOMERIZATION
Although the reaction is reversible, the
reaction proceeds readily in forming G3P from
DHAP.
TPI catalyzes the transfer of a hydrogen atom
in converting DHAP into G3P which is an
OXIDATION-REDUCTION reaction.
STEP 4
Occurrence
Km value
Affinity for
substrate
PHOSPHOFRUCTOKINASE
(PFK),
an
allosteric enzyme that sets the pace of
glycolysis
PHOSPHORYLATION of ATP to form another
monophosphate which is attached to C1 of the
fructose
the prefix bis in bisphosphate means two
seperate monophosphate groups are present
- inhibited by ATP; stimulated by
increase in ADP and AMP
STEP 6
NOTE:
o At this point, glycolysis has transformed one
molecule of glucose into 2 molecules of
glyceraldehyde 3-phosphate
o HARVEST TIME!!!
GLYCERALDEHYDE
3-PHOSPHATE
DEHYDROGENASE converts glyceraldehyde 3phosphate into 1,3-bisphosphoglycerate, by
PHOSPHORYLATION COUPLED TO OXIDATION
glyceraldehyde-3-phosphate
dehydrogenase- using NAD+ as a
cofactor and generating NADH worth 3
ATP or x 2= 6
- 3-Bisphosphoglycerate is an acyl
phosphate and is a high energy
compound.
STEP 9
2-phosphoglycerate phosphoenolpyruvate + H2O
STEP 10 (IRREVERSIBLE)
STEP 7
1,3-bisphosphoglycerate + ADP 3- phosphoglycerate +
ATP
Reactions 9 and 10
Inhibited by fluoride
STEP 8
3-phosphoglycerate 2-phosphoglycerate
STEP
1
3
6NADH
7
10
Total
+1 * 2 = 2
-1
-1
+3 * 2 = 6
+1 * 2 = 2
8 ATP
Note:steps 6, 7, and 10 were multiplied by two to account for the two 3 carbon sugars formed in Step 4
Pathway of Glycolysis:
Glucose
ATP
ADP
Hexokinase / Glucokinase
Glucose 6-Phosphate
Phosphohexose Isomerase
Fructose 6-Phosphate
ATP
ADP
Phosphofructokinase (PFK1)
Fructose-1,6-Biphosphate
Aldolase
DHAP
GLYC-3-P
Phosphotriose Isomerase
Phosphoric Acid
NAD
NADH (lost and used later)
Glyceraldehyde-3-Phosphate Dehydrogenase
OXIDATION STEP
1,3-BPG
SUBSTRATE LEVEL
PHOSPHORYLATION
3 Phosphoglycerate
ISOMERIZATION
Phosphoglycerate Mutase
(transfer of Phosphate)
2 Phosphoglycerate
DEHYDRATION
ADP
ATP (ATP is formed)
Phosphoglycerate Kinase
H2O
Enolase
Phosphoenolpyruvate
SUBSTRATE LEVEL
ADP + Pi
PHOSPHRYLATION
ATP
Pyruvate kinase
PYRUVATE
REDUCTION
Lactate Dehydrogenase
NADH (regenerated)
NAD
LACTATE
-Enzyme: Glyceraldehyde-3-Phosphate
Dehydrogenase
NAD-dependent
Consists of 4 identical
polypeptides (monomers) forming a tetramer
with -SH groups present on each polypeptide
one of the SH groups is the active site of the
enzyme
combines with the substrate forming a
thiolhemiacetal that is oxidized to a thiol ester
-Hydrogens removed in this oxidation are
transferred to NAD+
-Pi is added forming 1,3-biphosphoglycerate, and
the SH group is reconstituted
-2,3-biphosphoglycerate is an intermediate of
this reaction (2,3 BPG)
9. 2-Phosphoglycerate forms
Phosphoenolpyruvate
-Enzyme: Enolase
-inhibited by fluoride
-phosphate of phosphoenolpyruvate
transferred to ADP
REGULATION OF GLYCOLYSIS
o
o
GLYCOLYSIS TO TCAC
irreversible route oxidation of pyruvate to
acetyl-CoA
pyruvate from the cytosol is transported into
the mitochondrion and is oxidatively
decarboxylated
by
a
pyruvate
dehydrogenase complex
pyruvate dehydrogenase is regulated by:
o inhibition by its products, acetyl-CoA and
NADH
o phosphorylation by a kinase of three serine
residues, resulting in decreased activity
o dephosphorylation by a phosphatase, causing
increased activity
CLINICAL ASPECTS
Table 4: Summary
Reaction
Enzyme
Reaction
Type
Hexokinase/Gluc
okinase
Isomerase
Phosphoryl
transfer
Isomerization
Phosphofructoki
nase
Aldolase
Triose
phosphate
isomerase
Glyceraldehyde
3-phopsphate
dehydrogenase
Phosphoglycerat
e kinase
Mutase
2-phosphoglycerate phosphoenolpyruvate +
H2O
Phosphoenolpyruvate + ADP + H+ pyruvate +
ATP
Enolase
Phosphoryl
transfer
Aldol
cleavage
Isomerization
Phosphorylati
on coupled to
oxidation
Phosphoryl
transfer
Phosphoryl
shift
Dehydration