Glycolysis
Metabolism
- Glycolysis
Metabolism
Metabolism is the complete set of
chemical reactions that allow cells
to grow and divide.
Metabolic processes are divided into:
(1) Catabolism (eg glycolysis) –
reactions that breakdown complex
molecule into simple compounds
AND yield energy
Voet & Voet:
Chapter 11
(2) Anabolism (eg gluconeogenesis) –
reactions that create complex
molecule from simple compounds
AND utilize energy
Biochemistry 2000
Lecture 16
Slide 1
Lecture 16
Glucose Metabolism
Biochemistry 2000
Slide 2
Glycolysis
Glycolysis is a series of 10 enzyme catalyzed
reactions that converts β-D-glucose into
pyruvate and energy (2 ATP and 2 NADH)
There are three pathways that utilize
the majority of glucose in almost all
cells
Reactions 1-5 (Energy-investing or
preparatory phase)
2 ATP are consumed as glucose (6 carbons) is
converted to a form that can be split into two 3
carbon compounds
Reactions 6-10 (Energy-generating or payoff
phase)
Glycolytic and pentose
phosphate pathways
breakdown the majority
of glucose
2 ATP and 1 NADH are generated as each 3
carbon compound is dephsphorylated
Blue = Carbon
Purple = Phosphate
Lecture 16
Biochemistry 2000
Slide 3
Lecture 16
Biochemistry 2000
Slide 4
Energy Yield per Glucose
Glycolysis II.
Sequential reactions sharing a common intermediate have standard
free energy changes that are additive (coupling)
Glycolytic pathway showing structures of
all substrates and products
Glycolytic enzymes are listed on the far right
Glucose Degradation
Glucose + 2NAD+ 2 pyruvate + 2NADH + 2H+
∆G’ O= -146 kJ/mol
Important reaction are indicated by boxed
text on the left
ATP Formation
2ADP + 2P 2ATP + 2H O
∆G’ O= 61.0 kJ/mol
i
1
2
2
–
Includes all reactions that consume or
generate energy
----------------------------------------------------------------------------------------------------------
–
Includes cleavage of 6 carbon sugar into 3
carbon sugars
Overall Reaction
Glucose + 2NAD+ + 2ADP + 2P 2pyruvate + 2NADH + 2H+ + 2ATP + 2H O
i
2
O
O
O
∆G’S = ∆G’1 + ∆G’2 = -85 kJ/mol
Biochemistry 2000
Lecture 16
Slide 5
Glycolytic Enzymes
Reaction 1 and 3 consume ATP
–
Reactions 7 and 10 produce ATP
Slide 6
Hexokinase
Kinases are enzymes that transfer a phosphoryl group from a high energy
donor to an acceptor (ie. consume or produce ATP)
–
Biochemistry 2000
Lecture 16
Reaction 1: First ATP Utilization
Transfer of phosphoryl group from
ATP to the O6 of glucose
Isomerases and Mutases are enzymes that catalyze internal structural
rearrangements (no net gain or loss of atoms)
–
Reactions 2 and 5 are catalyzed by isomerases (carbonyl isomerization)
–
Reaction 8 is catalyzed by a mutase (phosphate changed position)
Enzyme undergoes conformational
change upon substrate binding
Remaining enzymes are all interesting/special
Aldolase – splits 6 carbon sugar into a pair of 3 carbon sugars
Excludes water and allows reaction
to proceed
Dehydrogenase – produces NADH (energy)
Enolase – produces phosphoenolpyruvate (a very high energy compound)
∆ G’° = -16.7 kJ/mol
Lecture 16
Biochemistry 2000
Slide 7
Lecture 16
Biochemistry 2000
Slide 8
Glucose-6-Phosphate
Isomerase
Phosphoglycerate Kinase
Reaction 7: First substrate
level phosphorylation
Reaction 2: Reversible isomerization of G6P to F6P
Like hexokinase – two lobes
swing together, exclude
water and allow
phosphorylation
aldose to ketose isomerization
prepares 6 carbon sugar for further phosphorylation
∆G’° = -18.5 kJ/mol
Note: all phosphoryl transfer reactions have
large negative ∆G’° changes as high
energy bonds are being broken
∆G’° = 1.7 kJ/mol
These reaction drive glycolysis
Biochemistry 2000
Lecture 16
Isomerization
Slide 9
Triose Phosphate Isomerase
Slide 10
Aldolase
Aldolase catalyzes cleavage of the 6 carbon sugar to a pair of 3 carbon
sugars (Reaction 4)
Reaction 5: Rapid, reversible
isomerization of DHAP to
G3P
Biochemistry 2000
Lecture 16
Complex 4 step mechanism
ketose to aldose isomerization
glyceraldehyde-3-phosphate (G3P)
Only G3P can continue down
the glycolytic pathway
∆G’° = 7.5 kJ/mol
fructose-1,6-bisphosphate (FBP)
Isomerase and mutase reaction
generally have small or positive
∆ G’° changes
dihydroxyacetone phosphate (DHAP)
∆G’° = 23.8 kJ/mol
Reactions are driven by constant
removal of product
Lecture 16
Biochemistry 2000
Slide 11
Lecture 16
Biochemistry 2000
Slide 12
Glyceraldehyde-3-phosphate
dehydrogenase
Enolase
Reaction 9: Enolase catalyzes dehydration of 2-phosphoglycerate to the
high energy compound, phosphoenolpyruvate (PEP)
Reaction 6: Oxidation of Glyceraldehyde-3-phosphate (G3P) to
1,3-bisphosphoglycerate (BPG)
(Another) Complex 4 step mechanism
C1 (red box) is oxidized as NAD+ is reduced to NADH
–
Mg2+ dependent reaction
NADH can provide energy via the electron transport chain (next lecture)
Overall Reaction:
G3P + NAD+ + Pi BPG + NADH + H+
∆G’° = 7.5 kJ/mol
Each of the “special” reactions (aldolase, dehydrogenase, enolase) are
unfavorable (have a positive ∆G’°)
∆G’° = 6.3 kJ/mol
Lecture 16
Biochemistry 2000
Slide 13
Lecture 16
Fates of Pyruvate and NADH
Biochemistry 2000
Slide 14
Metabolic
Summary
Glycolysis is one of two major metabolic
pathways that convert carbohydrates
into energy and simpler compounds
Pentose Phosphate is the other major
pathway
Pyruvate (under aerobic conditions) enters
Citric Acid Cycle
Lecture 16
Biochemistry 2000
Slide 15
Proteins are broken down to amino acids
and enter glycolysis and the citric acid cycle
Lipids are broken down to Fatty Acids and
glycerol and enter glycolysis and the citric
acid cycle
Lecture 16
Biochemistry 2000
Slide 16