Download Metabolism - Glycolysis

Metabolism
- Glycolysis
Voet & Voet:
Chapter 11
Lecture
16
Biochemistry 2000
Slide 1
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
(2) Anabolism (eg gluconeogenesis) –
reactions that create complex
molecule from simple compounds
AND utilize energy
Lecture
16
Biochemistry 2000
Slide 2
Glucose Metabolism
There are three pathways that utilize
the majority of glucose in almost all
cells
Glycolytic and pentose
phosphate pathways
breakdown the majority
of glucose
Lecture
16
Biochemistry 2000
Slide 3
Glycolysis
Glycolysis is a series of 10 enzyme catalyzed
reactions that converts -D-glucose into
pyruvate and energy (2 ATP and 2 NADH)
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)
●
2 ATP and 1 NADH are generated as each 3
carbon compound is dephsphorylated
Blue = Carbon
Purple = Phosphate
Lecture
16
Biochemistry 2000
Slide 4
Glycolysis II.
Glycolytic pathway showing structures of
all substrates and products
●
●
Glycolytic enzymes are listed on the far right
Important reaction are indicated by boxed
text on the left
–
Includes all reactions that consume or
generate energy
–
Includes cleavage of 6 carbon sugar into 3
carbon sugars
Lecture
16
Biochemistry 2000
Slide 5
Energy Yield per Glucose
Sequential reactions sharing a common intermediate have standard
free energy changes that are additive (coupling)
Glucose Degradation
Glucose + 2NAD+ → 2 pyruvate + 2NADH + 2H+
∆G’1O= -146 kJ/mol
ATP Formation
2ADP + 2Pi → 2ATP + 2H2O
∆G’2O= 61.0 kJ/mol
---------------------------------------------------------------------------------------------------------Overall Reaction
Glucose + 2NAD+ + 2ADP + 2Pi → 2pyruvate + 2NADH + 2H+ + 2ATP + 2H2O
∆G’SO= ∆G’1O + ∆G’2O = -85 kJ/mol
Lecture
16
Biochemistry 2000
Slide 6
Glycolytic Enzymes
Kinases are enzymes that transfer a phosphoryl group from a high energy
donor to an acceptor (ie. consume or produce ATP)
–
Reaction 1 and 3 consume ATP
–
Reactions 7 and 10 produce ATP
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)
Remaining enzymes are all interesting/special
Aldolase – splits 6 carbon sugar into a pair of 3 carbon sugars
Dehydrogenase – produces NADH (energy)
Enolase – produces phosphoenolpyruvate (a very high energy compound)
Lecture
16
Biochemistry 2000
Slide 7
Hexokinase
Reaction 1: First ATP Utilization
Transfer of phosphoryl group from
ATP to the O6 of glucose
Enzyme undergoes conformational
change upon substrate binding
Excludes water and allows reaction
to proceed
∆ G’° = -16.7 kJ/mol
Lecture
16
Biochemistry 2000
Slide 8
Phosphoglycerate Kinase
Reaction 7: First substrate
level phosphorylation
Like hexokinase – two lobes
swing together, exclude
water and allow
phosphorylation
∆G’° = -18.5 kJ/mol
Note: all phosphoryl transfer reactions have
large negative ∆G’° changes as high
energy bonds are being broken
●
Lecture
16
These reaction drive glycolysis
Biochemistry 2000
Slide 9
Glucose-6-Phosphate
Isomerase
Reaction 2: Reversible isomerization of G6P to F6P
●
aldose to ketose isomerization
●
prepares 6 carbon sugar for further phosphorylation
Isomerization
∆G’° = 1.7 kJ/mol
Lecture
16
Biochemistry 2000
Slide 10
Triose Phosphate Isomerase
Reaction 5: Rapid, reversible
isomerization of DHAP to
G3P
●
ketose to aldose isomerization
Only G3P can continue down
the glycolytic pathway
∆G’° = 7.5 kJ/mol
Isomerase and mutase reaction
generally have small or positive
∆G’° changes
●
Reactions are driven by constant
removal of product
Lecture
16
Biochemistry 2000
Slide 11
Aldolase
Aldolase catalyzes cleavage of the 6 carbon sugar to a pair of 3 carbon
sugars (Reaction 4)
●
Complex 4 step mechanism
glyceraldehyde-3-phosphate (G3P)
fructose-1,6-bisphosphate (FBP)
dihydroxyacetone phosphate (DHAP)
∆G’° = 23.8 kJ/mol
Lecture 16
Biochemistry 2000
Slide 12
Glyceraldehyde-3-phosphate
dehydrogenase
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
–
NADH can provide energy via the electron transport chain (next lecture)
Overall Reaction:
G3P + NAD+ + Pi ↔
BPG + NADH + H+
∆G’° = 6.3 kJ/mol
Lecture 16
Biochemistry 2000
Slide 13
Enolase
Reaction 9: Enolase catalyzes dehydration of 2-phosphoglycerate to the
high energy compound, phosphoenolpyruvate (PEP)
●
Mg2+ dependent reaction
∆G’° = 7.5 kJ/mol
Each of the “special” reactions (aldolase, dehydrogenase, enolase) are
unfavorable (have a positive ∆G’°)
Lecture 16
Biochemistry 2000
Slide 14
Fates of Pyruvate and NADH
Lecture
16
Biochemistry 2000
Slide 15
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
●
●
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