GLIKOLISIS• DOSEN PENGAMPU• PROF. DR. SABIRIN MATSJEH
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 monosaccharidesPentose phosphate shunt
Stored as glycogen in muscles and liver.
Glucose MetabolismGlucose Metabolism
GlycolysisGlycolysisWhat 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
Glycolysis has two stages.Glycolysis has two stages.
(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 overallplus two NADH.
Why oxidize glucose in stages?
G˚’ = -686 kcal/mol
• Direct combustion of glucose occurs at temperatures incompatible with life.
Glycolysis: Step 1
Hexokinase and glucokinase catalyzes irreversible phosphorylation of glucose (G-6-P).
OH
OH
H
OH
H
OHH
OH
CH2
O
PO32-
D-Glucose-6-phosphate( G-6-P )
OH
OH
H
OH
H
OHH
OH
CH2OH
D-Glucose
ATP ADP
Mg2+
hexokinase,glucokinase
Glycolysis: Step 2
Phosphoglucoisomerase converts G-6-P into fructose-6-phosphate (F-6-P).
Makes C1 of hexose available for phosphorylation.
OH
CH2OH
H
H OH
OH H
O
CH3
O
PO32-
D-Fructose-6-phosphate( F-6-P )
OH
OH
H
OH
H
OHH
OH
CH2
O
PO32-
D-Glucose-6-phosphate( G-6-P )
phosphoglucoisomerase
Glycolysis: Step 3
Phosphofructokinase (PFK-1) catalyzes irreversible phosphorylation of F-6-P to form fructose-1,6-diphosphate (F-1,6-DP).
OH
CH2
H
H OH
OH H
O
CH3
OO
PO32-PO3
2-
D-Fructose-1,6-diphosphate( F-1,6-DP )
OH
CH2OH
H
H OH
OH H
O
CH3
O
PO32-
D-Fructose-6-phosphate( F-6-P )
ATP ADP
Mg2+
phosphofructokinase
Glycolysis: Step 4
Fructose diphosphate aldolase catalyzes the cleavage of F-1,6-DP to form dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G-3-P).
CH2O
CH
OHCH
O
PO32-
D-Glyseraldehide-3-phosphate
H2C
O
HOH2C
O
Dihydroxy acetone phosphate
PO32-
( DHAP )( G-3-P )
+
fructosediphosphate
aldolase
OH
CH2
H
H OH
OH H
O
CH3
OO
PO32-PO3
2-
D-Fructose-1,6-diphosphate( F-1,6-DP )
Glycolysis: Step 5
Triose phosphate isomerase converts DHAP to G-3-P.
G-3-P continues through glycolysis.
Triosa phosphate isomerase
H2C
O
HOH2C
O
Dihydroxy acetone phosphate
PO32-
( DHAP )
CH2O
CH
OHCH
O
PO32-
D-Glyseraldehide-3-phosphate( G-3-P )
Glycolysis: Step 6
G-3-P dehydrogenase catalyzes oxidation and phosphorylation of G-3-P to form 3-Phosphoglyceroil phosphate
CH2O
CH
OHCH
O
PO32-
D-Glyseraldehide phosphatedehydrogenase
NADH + H+
NAD+Pi
D-Glyseraldehide-3-phosphate
CH2O
CH
OHC
O
PO32-
3-Phosphoglyceroil phosphate
O
PO32-
Glycolysis: Step 7
Phosphoglycerate kinase (PGK) transfers phosphate from 3-PGP to ADP to form ATP (substrate-level phosphorylation) and 3-phosphoglycerate (3-PG).
CH2O
CH
OHC
O
PO32-
3-Phosphoglyceroil phosphate
O
PO32-
CH2O
CH
OHC
O
PO32-
O-
3-Phosphoglycerate
ADP ATP
Mg2+
Phosphoglycerate kinase
Glycolysis: Step 8
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.
CH2O
CH
OHC
O
PO32-
O-
3-Phosphoglycerate
CH2OH
CH
OC
O
O-
PO32-
2-Phosphoglycerate
Mg2+
Phosphoglycerate mutase
Glycolysis: Step 9
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.
CH2OH
CH
OC
O
O-
PO32-
2-Phosphoglycerate
CH2
C
OC
O
O-
PO32-
Phosphoenolpyruvate
K+,Mg2+
enolase
Glycolysis: Step 10
Pyruvate kinase catalyzes irreversible transfer of phosphate from PEP to ADP to form ATP (2nd substrate-level phosphorylation) and pyruvate.
CH2
C
OC
O
O-
PO32-
Phosphoenolpyruvate
ADP ATPMg2+
Pyruvate kinase
CH3
C
C
O
O-
O
Pyruvate
PyruvatePyruvate
Alcohol AnaerobicAlcohol Anaerobic FermentationFermentation GlycolysisGlycolysis
Aerobic GlycolysisAerobic Glycolysis
What Happens to Pyruvate?
-PyruvatePyruvate can be further processed:
a) anaerobically : to lactatelactate in muscle
b) anaerobically : to ethanolethanol (fermentation)
c) aerobically to CO2 and H2O via the citric acid cycle.
a) Lactic Acid Fermentation
• Occurs in muscles.
O
O
O-
pyruvateOH
O
O-
lactate
NADH + H+ NAD+
Siklus Cory
Liver Glycogen
Blood GlucoseLactate acid
Muscle Glycogen
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
Glikogen
Glukosa1-fosfat
Glukosa6-fosfat
Fruktosa6-fosfat
Fruktosa1,6-difosfat
Gliseraldehida3-fosfat
OH
H
H
OH
H
OHH
OH
CH2OH
O
D-Galaktosa
OH
CH2OH
H
OH H
H OH
CH2OHO
D-Fruktosa
OH
OH
H
OH
H
OHH
OH
CH2OH
D-Glukosa
OH
OH
H
OH
OH
HH
OH
CH2OH
D-manosa
UDP-galaktosa
UDP-glukosa
Manosa 6-fosfat
Fruktosa 1-fosfat
Gliseraldehida + Dehidroksiaseton fosfat
Metabolism of Other Sugars
ATP
ATP
ATP
ATP
ATP
Pi
fosforilase
Fosfogluko-mutase
heksokinase
Fosfomano-isomerase
heksokinase
heksokinase
fruktokinase
triosa kinase
triosa fosfatisomerase
Fruktosa fosfat aldolase
SummarySummary GlucoseGlucoseof Reactionsof Reactions 2 ATP 2 NADH 2 pyruvate 2 NADH 2 NADH anaerobicanaerobic anaerobicanaerobic 2 ethanol + CO2 2 lactate
2 CO2 + 2 acetyl CoA
O2 aerobicaerobic
4 CO2 + 4 H2O
Summary of Energy Relationship for Summary of Energy Relationship for GlycolysisGlycolysis
Input = 2 ATP 1. glucose + ATP glucose-6-P 2. fructose-6-P + ATP fructose 1,6
diphosphateOutput = 4 ATP + 2 NADHa. 2 glyceraldehyde-3-P + 2 Pi + 2 NAD+ 2 (3-phosphoglyceroil phosphate) + 2 NADHb. 2 (3-phosphoglyceroil phosphate) + 2 ADP 2 (3-P-glycerate) + 2 ATPc. 2 PEP + 2 ADP 2 pyruvate + 2 ATPNet = 2 ATP and 2 NADH
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