Chapter 16- Glycolysis

Just right. Suggest some possible reasons why glucose is
fuel used by all organisms.
Glucose is formed under prebiotic conditions. It is the most
stable hexose sugar and consequently, has a low tendency, relative to
other monosaccharides, to nonenzymatically react with proteins.

Hexokinase
Generates the second
molecule
of ATP

Phosphoglucose
isomerase
Converts glucose
6-phosphate
into fructose
6-phosphate

Phosphofructokinase
Forms fructose
1,6-bisphosphate

Aldolase
Cleaves fructose
1,6-bisphosphate

Triose phosphate isomerase
Catalyzes the
interconversion
of

Glyceraldehyde 3-phosphate dehydrogenase
Generates the first highphosphoryl-
transferpotential
compound that
is not ATP

Phosphoglycerate kinase
Generates the first molecule
of ATP

Phosphoglycerate mutase
Converts 3-phosphoglycerate
into 2-phosphoglycerate

Enolase
Generates the second
high-phosphoryl-transfer-
potential compound
that is not ATP

Pyruvate kinase
Generates the second
molecule
of ATP

Who takes? Who gives? Lactic acid fermentation and
alcoholic fermentation are oxidation-reduction reactions.
Identify the ultimate electron do
In both cases, the electron donor is glyceraldehyde 3-phosphate.
In lactic acid fermentation, the electron acceptor is pyruvate,
converting it into lactate. In alcoholic fermentation, acetaldehyde is
the electron acceptor, forming ethanol.

ATP yield. Each of the following molecules is processed
by glycolysis to lactate. How much ATP is generated from
each molecule?
(a) Glucose 6-phosphate
(b) Dihydroxyacetone phosphate
(c) Glyceraldehyde 3-phosphate
(d) Fructose
(e) Sucrose
(a) 3 ATP; (b) 2 ATP; (c) 2 ATP; (d) 2 ATP; (e) 4 ATP

Enzyme redundancy? Why is it advantageous for the
liver to have both hexokinase and glucokinase to phosphorylate
glucose?
Glucokinase enables the liver to remove glucose from the blood
when hexokinase is saturated, ensuring that glucose is captured for
later use.

Enzyme properties. In the liver and the pancreas, hexokinase
and glucokinase phosphorylate glucose. Glucokinase
is active only when the blood concentration of glucose
is high. How might glucokinase differ kinetically from
hexokinase so as to function only at high glucose levels?
Glucokinase has a higher KM value, which allows this enzyme to
become more active at high glucose concentrations, conditions that
saturate hexokinase.

Required isomerization. Why is the isomerization of
glucose 6-phosphate to fructose 6-phosphate an important
step in glycolysis? How is the conversion of the fructose
isomer back into the glucose isomer prevented?
Glucose cannot be cleaved into two three-carbon fragments,
whereas fructose can, and three-carbon molecules are metabolized
in the second stage of glycolysis. The conversion of fructose
6-phosphate into fructose 1,6-bisphosphate prevents the glucose
isomer from being re-formed.

Magic? The interconverison of DHAP and GAP greatly
favors the formation of DHAP at equilibrium. Yet the conversion
of DHAP by triose phosphate isomerase proceeds
readily. Why?
The GAP formed is immediately removed by subsequent
reactions, resulting in the conversion of DHAP into GAP by the
enzyme

Between two extremes. What is the role of a thioester in
the formation of ATP in glycolysis?
A thioester couples the oxidation of glyceraldehyde
3-phosphate to 3-phosphoglycerate with the formation of
1,3-bisphosphoglycerate. 1,3-Bisphosphoglycerate can subsequently
power the formation of ATP.

Corporate sponsors. Some of the early research on
glycolysis
was supported by the brewing industry. Why
would the brewing industry be interested in glycolysis?
Glycolysis is a component of alcoholic fermentation, the
pathway that produces alcohol for beer and wine. The belief was that
understanding the biochemical basis of alcohol production might
lead to a more efficient means of producing

Recommended daily allowance. The recommended
daily allowance for the vitamin niacin is 15 mg per day.
How would glycolysis be affected by niacin deficiency?
The conversion of glyceraldehyde 3-phosphate into
1,3-bisphosphoglycerate would be impaired. Glycolysis would be
less effective.

Running in reverse. Why can’t the reactions of the
glycolytic
pathway simply be run in reverse to synthesize
glucose?
The DG°′ for the reverse of glycolysis is +90 kJ mol−1 (+22 kcal
mol−1), far too endergonic to take place.

Destiny. What are the principle fates of pyruvate generated
in glycolysis?
Pyruvate can be metabolized to ethanol in alcoholic
fermentation, to lactate in lactic acid fermentation, or be completely
oxidized to CO2 and H2O in cellular respiration.

Road blocks. What reactions of glycolysis are irreversible
under intracellular conditions?
The conversion of glucose into glucose 6-phosphate by
hexokinase; the conversion of fructose 6-phosphate into fructose
1,6-bisphosphate by phosphofructokinase; the formation of pyruvate
from phosphoenolpyruvate by pyruvate kinase

No pickling. Why is it in the muscle’s best interest to
export lactic acid into the blood during intense exercise?
Lactic acid is a strong acid (problem 2.15). If it remained
in the cell, the pH of the cell would fall, which could lead to the
denaturation of muscle protein and result in muscle damage.

Diverted resources. Phosphofructokinase converts fructose
6-phosphate to fructose 1,6-bisphosphate, the committed
step on the pathway that synthesizes ATP. However, some
fructose 6-phosphate is converted into fructose 2,6-bisphosphate.
Explain why depleting the substrate of PFK to form
fructose 2,6-bisphosphate is not a wasteful use of substrate.
Recall from our discussion of enzyme kinetics in Chapter 7
that substrates are usually present in much higher concentration
than their enzymes. Consequently, converting a small amount of
substrate into a potent activator of PFK will lead to a rapid increase
in the rate of ATP synthesis.

Glucose
6-phosphate
Inhibits hexokinase

Low ATP/AMP
ratio
Stimulates phosphofructokinase

Citrate
Inhibits phosphofructokinase
in the liver

Low pH
Inhibits phosphofructokinase
in muscle

Fructose
1,6-bisphosphate
Stimulates pyruvate
kinase

Fructose 2,6-
bisphosphate
Stimulates phosphofructokinase
in the liver

Insulin
Causes the insertion of
GLUT4 into cell membranes

Has a high KM for
glucose
Glucokinase

Transporter specific to
liver and pancreas
GLUT2

High ATP/AMP
ratio
Inhibits phosphofructokinase

Not MTV. A ligand-gated ion channel and a voltagegated
ion channel play keys roles in the secretion of insulin
by the pancreas. What are the channels, and what is their
function in insulin secretion?
A potassium channel, a ligand-gated channel, is inhibited by
binding ATP. This inhibition alters the voltage across the plasma
membrane, which activates a calcium channel, a voltage-gated
channel, allowing an influx of calcium ions. The calcium ions
stimulate the fusion of insulin-containing granules with the plasma
membrane, resulting in the secretion of insulin.