What is glycolysis?
Ten step metabolic pathway to convert glucose into two molecules of pyruvate and two molecules each of NADH and ATP.
All carbohydrates to be catabolized must enter the glycolytic pathway.
Glycolysis is central in generating both energy and metabolic intermediaries.
Also known as Embden-Meyerhof-Parnas (EMP) pathway
2. Fate of glucose
Completely oxidized to CO2 and H2O.
Cellular respiration
Converted to lactate.
Cori cycle converts lactate back to glucose.
Converted to acetyl CoA.
Enters Kreb’s cycle* or is used to synthesize fat.
Converted to other monosaccharides
Pentose phosphate shunt
Stored as glycogen in muscles and liver.
4. GGllyyccoollyyssiiss
What is glycolysis?
Ten step metabolic pathway to convert glucose into
two molecules of pyruvate and two molecules each of
NADH and ATP.
All carbohydrates to be catabolized must enter the
glycolytic pathway.
Glycolysis is central in generating both energy and
metabolic intermediaries.
Also known as Embden-Meyerhof-Parnas (EMP) pathway
5. LINTAS GLIKOLISIS DAN GLUKONEOGENESIS
ATP
ADP
Malat Malat
Oksaloasetat
NAD+
Oksaloasetat ADP
ATP CO2
ATP
ADP
ATP
F6P(fruktosa-6-phospat)
ATP
ADP
NAD+
NADH
H2O ADP
Pi
Piruvat
NADH
GTP
GDP CO2
NAD+
NADH
MITOKONDRIA
SITOSOL
DHAP
Glukosa
G6P(Glukosa-6-phospat)
F 1,6 DP (fruktosa-1,6-diphospat)
G3P(gliseraldehid-3-phospat)
3PGP(pospogliseroil phospat)
3PG
(phospogliserat)
2PG PEP
(phospo enol piruvat)
Piruvat
6. GGllyyccoollyyssiiss hhaass ttwwoo ssttaaggeess..
(i) An energy investment phase. Reactions, 1-5. Glucose
to two glyceraldehyde -3-phosphate molecules. 2
ATPs are invested.
(ii) An energy payoff phase. Reactions 6-10.
two glyceraldehyde 3-phosphate molecules
to two pyruvate plus four ATP molecules.
-- A net of two ATP molecules overall
plus two NADH.
7. Why oxidize glucose in stages?
D G˚’ = -686 kcal/mol
• Direct combustion of glucose occurs at
temperatures incompatible with life.
8. Glycolysis: Step 1
PO3
O
CH2
2-
H O
OH
H
OH
H
OH
H OH
D-Glucose-6-phosphate
( G-6-P )
CH2OH
H O
OH
H
OH
H
OH
H OH
D-Glucose
ATP ADP
Mg2+
hexokinase,
glucokinase
Hexokinase and glucokinase catalyzes
irreversible phosphorylation of glucose (G-6-
P).
9. Glycolysis: Step 2
CH2OH
OH
PO3
O
2-
CH3
H
O
OH H
H OH
D-Fructose-6-phosphate
( F-6-P )
PO3
O
CH2
2-
H O
OH
H
OH
H
OH
H OH
D-Glucose-6-phosphate
( G-6-P )
phosphoglucoisomerase
Phosphoglucoisomerase converts G-6-P into fructose-
6-phosphate (F-6-P).
Makes C1 of hexose available for phosphorylation.
10. Glycolysis: Step 3
PO3 2-
O O
CH2
O
OH H
CH2OH
O
2-
OH H
PO3
O
Phosphofructokinase (PFK-1) catalyzes irreversible
phosphorylation of F-6-P to form fructose-1,6-
diphosphate (F-1,6-DP).
OH
H
H OH
CH3
PO3
2-
D-Fructose-1,6-diphosphate
( F-1,6-DP )
OH
H
H OH
CH3
D-Fructose-6-phosphate
( F-6-P )
ATP ADP
Mg2+
phosphofructokinase
11. Glycolysis: Step 4
CH2O
CH
OH CH
O
PO3
2-
PO3 2-
O O
CH2
O
OH H
Fructose diphosphate aldolase catalyzes the
cleavage of F-1,6-DP to form
dihydroxyacetone phosphate (DHAP) and
glyceraldehyde-3-phosphate (G-3-P).
PO3
2-
D-Glyseraldehide-3-
phosphate
H2C
O
HOH2C
O
Dihydroxy acetone phosphate
( DHAP )
( G-3-P )
+
fructose
diphosphate
aldolase
OH
H
H OH
CH3
PO3
2-
D-Fructose-1,6-diphosphate
( F-1,6-DP )
12. Glycolysis: Step 5
PO3
2-
Triosa phosphate isomerase
H2C
O
HOH2C
O
Dihydroxy acetone phosphate
( DHAP )
CH2O
CH
OH CH
O
PO3
2-
D-Glyseraldehide-3-phosphate
( G-3-P )
Triose phosphate isomerase converts DHAP
to G-3-P.
G-3-P continues through glycolysis.
13. Glycolysis: Step 6
CH2O
CH
OH CH
O
PO3
2-
G-3-P dehydrogenase catalyzes oxidation and
phosphorylation of G-3-P to form 3-
Phosphoglyceroil phosphate
O
PO3
2-
D-Glyseraldehide
phosphate
dehydrogenase
NADH + H+
Pi NAD+
D-Glyseraldehide-3-phosphate
CH2O
CH
C OH
O
PO3
2-
3-Phosphoglyceroil phosphate
14. Glycolysis: Step 7
CH2O
CH
C OH
O
PO3
2-
O
PO3
2-
3-Phosphoglyceroil phosphate
CH2O
CH
C OH
O
Phosphoglycerate kinase (PGK) transfers
phosphate from 3-PGP to ADP to form ATP
(substrate-level phosphorylation) and 3-
phosphoglycerate (3-PG).
PO3
2-
O-
3-Phosphoglycerate
ADP ATP
Mg2+
Phosphoglycerate kinase
15. Glycolysis: Step 8
CH2O
CH
C OH
2-
3-PG is converted to 2-PG by phosphoglycerate
mutase.
Moving phosphate closer to carboxyl group makes
molecule more unstable ( G) and thus more likely to
transfer phosphate to another substrate.
O
PO3
O-
3-Phosphoglycerate
CH2OH
CH
C O
O
O-PO3
2-
2-Phosphoglycerate
Mg2+
Phosphoglycerate mutase
16. Glycolysis: Step 9
CH2OH
CH
C O
Dehydration of 2-PG to form phosphoenolpyruvate
(PEP) is catalyzed by enolase.
Traps PEP in enol form (tautomer), which is very
unstable facilitating transfer of phosphate to ADP in
step 10.
O
O-PO3
2-
2-Phosphoglycerate
CH2
C
C O
O
O-PO3
2-
Phosphoenolpyruvate
K+,Mg2+
enolase
17. Glycolysis: Step 10
CH2
C
C O
O
O-PO3
2-
Phosphoenolpyruvate
ADP ATP
Mg2+
Pyruvate kinase
Pyruvate kinase catalyzes irreversible transfer of phosphate
from PEP to ADP to form ATP (2nd substrate-level
phosphorylation) and pyruvate.
CH3
C
C
O
O-O
Pyruvate
18. What Happens to Pyruvate?
PyruvatPyruvatee
AAllccoohhooll AAnnaaeerroobbiicc
FFeerrmmeennttaattiioonn GGllyyccoollyyssiiss
AAeerroobbiicc GGllyyccoollyyssiiss
19. -PPyyrruuvvaattee can be further processed:
a) anaerobically : to llaaccttaattee in
muscle
b) anaerobically : to eetthhaannooll
(fermentation)
c) aerobically to CO2 and H2O via the
citric acid cycle.
20. a) Lactic Acid Fermentation
O
O
O-pyruvate
• Occurs in muscles.
OH
O
O-lactate
NADH + H+ NAD+
22. b) Alcoholic Fermentation
O
O
O-pyruvate
+ H+
CO2
O
acetaldehyde
HO
ethanol
NADH+H+ NAD+
1 2
1. Pyruvate decarboxylase – irreversible
2. Alcohol dehydrogenase – reversible
Note : NADH used up
23. Metabolism of Other Sugars
Glikogen
Glukosa
1-fosfat
Glukosa
6-fosfat
Fruktosa
6-fosfat
Fruktosa
1,6-difosfat
Gliseraldehida
3-fosfat
OH
H
H
OH
O
H
CH2OH
OH
H OH
D-Galaktosa
CH2OH
OH
CH2OH
H O
CH2OH
H
O
OH
H OH
OH H
D-Fruktosa
OH
H
OH
H
H OH
D-Glukosa
CH2OH
H O
OH
H
OH
OH
OH
H H
D-manosa
UDP-galaktosa
UDP-glukosa
Manosa 6-fosfat
ATP
Fruktosa 1-fosfat
ATP
Fruktosa fosfat aldolase
Gliseraldehida + Dehidroksiaseton fosfat
ATP
ATP
ATP
Pi
fosforilase
Fosfogluko-mutase
heksokinase
Fosfomano-isomerase
heksokinase
heksokinase
fruktokinase
triosa kinase
triosa fosfat
isomerase
24. SSuummmmaarryy GGlluuccoossee
ooff RReeaaccttiioonnss 2 ATP
2 NADH
2 pyruvate
2 NADH 2 NADH
aannaaeerroobbiicc aannaaeerroobbiicc
2 ethanol + CO2 2 lactate
2 CO2 + 2 acetyl CoA
O2 aaeerroobbiicc
4 CO2 + 4 H2O
25. SSuummmmaarryy ooff EEnneerrggyy RReellaattiioonnsshhiipp ffoorr
GGllyyccoollyyssiiss
Input = 2 ATP
1. glucose + ATP glucose-6-P
2. fructose-6-P + ATP fructose 1,6
diphosphate
Output = 4 ATP + 2 NADH
a. 2 glyceraldehyde-3-P + 2 Pi + 2 NAD+
2 (3-phosphoglyceroil phosphate) + 2 NADH
b. 2 (3-phosphoglyceroil phosphate) + 2 ADP
2 (3-P-glycerate) + 2 ATP
c. 2 PEP + 2 ADP 2 pyruvate + 2 ATP
Net = 2 ATP and 2 NADH