Download Recitation 4: glycolysis, gluconeogenesis, and the citric acid cycle

Recitation 4: glycolysis,
gluconeogenesis, and the
citric acid cycle
Bi/Ch 110
November 16, 2016
Announcements
• Revised office hours:
• Camille: Weds 1-2pm SFL 229
• Emily: Fri 4-5pm SFL 229
• Due dates:
• Pset 4 due Tues, Nov 22
• Pset 5 going out Tues Nov 22, due Dec 1
Agenda
• Questions about Pset 3?
• Review of metabolism thus far
• Practice problems
• Questions about Pset 4?
Basics of metabolism
• ATP is the cell’s energy currency
• Catabolism: turning carbon fuels into ATP
• glycolysis, the citric acid cycle
• Fuel  CO2 + H2O + energy
• Metabolism: using energy from ATP
• Synthesis of fats, amino acids, nucleotides and complex
biological molecules
• ΔG must be negative for the entire set of reactions
Where does the energy come
from?
• Oxidation of carbon
atoms goes through a
high-phosphoryl-transferpotential compound,
which is then used to
generate ATP
• Electrons from oxidation
are transferred to an
activated carrier such as
NAD+
• Oxidation of more
complex fuels happens
one carbon at a time
What carries the electrons?
What carries the electrons?
Overview of catabolism
Overview of catabolism
Glycolysis
Overview of catabolism
Citric Acid Cycle
Reactions of glycolysis
• Glucose is imported
into cytoplasm via
transport proteins
• First
phosphorylation
traps glucose in the
cell
• Isomerization and
phosphorylation
ensures that aldol
cleavage creates
two interconvertible
three-carbon
molecules
Reactions of glycolysis
• Oxidation of aldehyde
generates NADH and ATP
• Shift of phosphoryl group
creates a high
phosphoryl-transfer
potential because
phosphoenolpyruvate is
trapped in the unstable
enol form rather than the
stable ketone
Overall reaction of glycolysis
glucose + 2 NAD+ + 2 Pi + 2 ADP 
2 pyruvate + 2 NADH + 2 H+ + 2 ATP + 2 H2O
Keeping redox balance
Anaerobic
The fate of pyruvate in aerobic
respiration: acetyl CoA
• Pyruvate dehydrogenase complex converts the output
of glycolysis (pyruvate) into the input for the citric acid
cycle (acetyl CoA)
• Takes place in the mitochondrial matrix
• Produces one NADH
The citric acid cycle
• Takes place in the
mitochondrial matrix
• Works on 2-carbon
units
• Begins with transfer
of acetyl group onto
oxaloacetate and
ends with
regeneration of
oxaloacetate after
release of 2 CO2
Overall reaction of the citric acid
cycle
acetyl CoA + 3 NAD+ + FAD + Pi + ADP + H2O 
CoA + 3 NADH + FADH2 + 2 H+ + ATP + 2 CO2
Gluconeogenesis
• Turns non-carbohydrate precursors into glucose
• Lactate (recycled from anaerobic respiration)
• Amino acids
• Glycerol
• Precursors enter in as pyruvate (lactate, aa’s),
oxaloacetate (aa’s) or dihydroxyacetone phosphate
(glycerol)
• Takes place in the liver to regulate blood glucose
levels
Gluconeogenesis is not a reversal
of glycolysis
Reactions of gluconeogenesis
• Unique reactions shown in
red
• Overall reaction:
2 pyruvate + 4 ATP + 2 GTP +
2 NADH + 6 H2O 
glucose + 4 ADP + 2 GDP + 6 Pi
+ 2 NAD+ + 2 H+
Which reactions should be
regulated?
Which reactions should be
regulated?
Metabolic regulation
• Typically the irreversible steps
• How?
• Controlling amounts of enzymes via transcription
• Controlling catalytic activity via allostery or covalent
modification
• Energy sensors: ATP/ADP/AMP, NAD+/NADH
• Products
• Downstream molecules
• Controlling availability of substrates
Glycolysis and gluconeogenesis
are reciprocally regulated
Practice Problems
Practice question 1
a)
What makes ATP such a useful cellular “energy currency”?
b)
Based on the table, which direction will the following reactions run given
equimolar amounts of reactants?
i.
ATP + creatine  creatine phosphate + ADP
ii.
ATP + glycerol  glycerol 3-phosphate + ADP
Practice question 1
a)
What makes ATP such a useful cellular “energy currency”?
It has an intermediate phosphoryl-transfer potential so it can act both as a phosphoryl
donor and acceptor for important biomolecules. See textbook Figure 15.6, page 430.
b) Based on the table, which direction will the following reactions run given equimolar
amounts of reactants?
i.
ATP + creatine  creatine phosphate + ADP
Forward reaction: -30.5 kJ/mol
Reverse reaction: -43.1 kJ/mol
ii.
ATP + glycerol  glycerol 3-phosphate + ADP
Forward reaction: -30.5 kJ/mol
Reverse reaction: -9.2 kJ/mol
Practice question 2
If glucose is labeled with 14C
on the C2 carbon circled
below, where does that
label end up if the end
product of metabolism is
ethanol?
Practice question 2
If glucose is labeled with 14C
on the C2 carbon circled
below, where does that
label end up if the end
product of metabolism is
ethanol?
Practice question 3
Explain why your muscles feel sore/burning after
intense exercise.
Practice question 3
Explain why your muscles feel sore/burning after
intense exercise.
After intense exercise, muscle tissue will run out of
oxygen. Therefore, the muscle cannot use aerobic
respiration (citric acid cycle and oxidative
phosphorylation) to regenerate ATP and instead must
use anaerobic respiration. The product of anaerobic
respiration is lactate, or lactic acid, which produces a
burning sensation in the muscle due to low pH.
Practice question 4
How much ATP would be generated from each of the
following molecules if it were processed fully to
lactate?
a) Glyceraldehyde 3-phosphate
b) Fructose
Practice question 4
How much ATP would be generated from each of the
following molecules if it were processed fully to
lactate?
a) Glyceraldehyde 3-phosphate 2 ATP
b) Fructose 2 ATP
Practice question 5
How many ATP/GTP
molecules are needed to
make glucose from each of
the following precursors?
a) Two molecules of
oxaloacetate
b) Fructose 1,6bisphosphate
Practice question 5
How many ATP/GTP
molecules are needed to
make glucose from each of
the following precursors?
a) Two molecules of
oxaloacetate
4 ATP/GTP
a) Fructose 1,6bisphosphate
0 ATP/GTP
Practice question 6
At equilibrium, 96% of the triose phosphate is
dihydroxyacetone phosphate rather than
glyceraldehyde 3-phosphate. However, the reaction
to produce glyceraldehyde 3-phosphate proceeds.
Why?
Practice question 6
At equilibrium, 96% of the triose phosphate is
dihydroxyacetone phosphate rather than
glyceraldehyde 3-phosphate. However, the reaction
to produce glyceraldehyde 3-phosphate proceeds.
Why?
The rest of the reactions of glycolysis use up
glyceraldehyde 3-phosphate, removing the product
of the reaction and therefore driving it forward.