P.10.

GLYCOLYSIS AND THE OXIDATION OF

PYRUVATE (PART 1)
Dr. Salango | February 8, 2018

 The glycolytic pathway is employed by ALL tissues

OUTLINE for the oxidation of glucose to provide energy (in
I. Overview of Glycolysis the form of ATP) and intermediates for other
II. Aerobic and Anaerobic Glycolysis metabolic pathways.
III. Glycolysis  It is a hub of carbohydrate metabolism because
A. Phases of glycolysis virtually all sugars, whether arising from the diet or
IV. Reactions of Glycolysis : Preparative from catabolic reactions in the body, can ultimately
A. Phosphorylation of Glucose be converted to glucose.
B. Isomerization of Glucose-6-  ATP, Carbohydrates and fats are converted into fuel
Phosphate sources.
 Pyruvate is the end product of glycolysis in
V. cells with mitochondria and an adequate supply of
oxygen.
 IMPORTANT TO REMEMBER:
o In terms of the pathway, it shows that we
I. Overview of Glycolysis can derive energy from fats, CHO,
proteins, and nucleic acids. Nucleic acids
are the ones responsible for the actual
ATP (energy).
o CHO generally enter the final phase which
is the Krebs Cycle, but there are
intermediaries that can enter much of the
glycolytic pathway. For instance, amino
acids entering via pyruvate.
o All processes in glycolysis, happen in the
cytoplasm. Therefore, it being in the
cytoplasm, the reactions are rather fast
and quick. All of the reactions, as long as
there are enzymes, they are fast and quick
but the problem is that in order for energy
to be produced, it has to go inside the
mitochondria, and that takes a little more
time. It may be in milliseconds, but that
millisecond difference is already
significant. Hence, if ATP (energy) is
needed right away, it is better to produce
it via the cytoplasmic route and that is via
the glycolysis.
o Strictly speaking, the final pathway of
glycolysis is either pyruvate or lactic acid.

 Can all fatty acids can be converted to

proteins?
o NO. Except odd numbered fatty acids. 3
carbon end derivatives follow a specific
pathway for conversion.
 Sometimes, glycolysis is known to be a pathway
that connects all other pathways because fatty acid
and protein degradation can proceed to this
pathway.
 Technically, glycolysis is only the conversion
of glucose to acetyl-CoA. Sometimes, glycolysis
ends only after producing pyruvate or lactate
 GLYCOLYSIS IS NOT OXYGEN DEPENDENT
BUT AEROBIC GLYCOLYSIS PREDOMINATE.
 It is not an energy efficient way of producing
energy, one molecule of glucose will only
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 produce 2 moles of ATP thus used only for
emergency states.
 In vegetative state, fats are first used to conserve
glucose or carbs for emergency states.
 The brain cannot use lipids for energy;it is specific
only for glucose. Energy utilization of brain
whether in a resting or active state, is always the
same. Consumption of brain is constant 24/7.
II. Aerobic and Anaerobic Glycolysis
 AEROBIC GLYCOLYSIS
- The glycolytic pathways occurs in the cytoplasm while
the TCA occurs in the mitochondria
- Greatest release of energy
- Product: Pyruvate
- Pyruvate is produced that will enter the TCA cycle for
the production of 38 moles of ATP
- TCA cycle is the only part of the process that will
require OXYGEN for ATP generation, therefore, this is
considered an integral part of this pathway
 ANAEROBIC GLYCOLYSIS
- Occurs in the cytoplasm only
- Moderately Efficient
- Product: Lactate
- Lactate is produced through the action of lactate
dehydrogenase
 Cellular respiration occurs in two distinct stages. First,
glucose is converted to pyruvate. The outcome of the
second stage depends on the presence of oxygen.
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 So if there is enough oxygen in the system, then the final
product is pyruvate. If oxygen is lacking, then the final
product is lactic acid.
 PYRUVATE DEHYDROGENASE COMPLEX: it serves as
the mediator of the conversion of pyruvate to acetyl CoA
-- it is also a very good regulatory enzyme because when
fatty acids are around, this enzyme is inhibited. This is what
we call the “RANDLE EFFECT” - this is the whole basis in
the activities that we do, especially those activities that
require aerobic and anaerobic glycolysis that may shift to
lipid beta-oxidation. This is because when fatty acids come
into the picture, they block further conversion of glucose to
pyruvate and acetyl co-enzyme A. The purpose of this is to
preserve the glucose for emergency purposes, or an
assurance of a steady supply in the brain.
For example:
Flight or fight activities = cell is using glycolysis
Resting = cell is using lipids
 Look at the nature of the muscles being used: Slow twitch
vs. Fast twitch
*Constriction in the eyes: Iris is using smooth muscles
Smooth muscles, the contraction is high
(regular contraction) => FATS/LIPIDS
*Thumb muscle = using fast twitch => GLUCOSE
*Gluteus maximus = using slow twitch => LIPIDS
THEREFORE, our body is a balance depending on the
activities that we are doing. It can be dominantly using
glucose or fats.
 RESPIRATORY QUOTIENT: The respiratory quotient of 1,
meaning the amount of oxygen being used is the same
amount of carbohydrates being produced, then you are
using fats.
All FATS = 1
All CHO = .8
All PROTEINS = .7
III. Glycolysis
 Principal route for glucose metabolism and major
pathway for the metabolism of fructose, galactose, and
other carbohydrates derived from diet.
 Occurs in cytosol of all cells
 Can function aerobically (product: pyruvate) or
anaerobically (product: lactate)
 Consists of:
o Initial preparative phase:
the phosphorylated forms of intermediates are
synthesized at the expense of ATP
o ATP generating phase:
a net of two molecules of ATP are formed by
substrate-level phosphorylation per glucose
molecule metabolized
 There are two different pathways:
Glucose -> pyruvate if there are sufficient oxygen levels =>
AEROBIC GLYCOLYSIS, but technically oxygen is not
involved in the whole process. This is actually a misnomer,
oxygen is never involved in the glycolysis. But, if you look at
the whole process of glycolysis, it is actually an oxidative
YU, J| JIMENEZ, EJ|DUMLAO, N
 reaction. So when glucose is broken down to pyruvate or
lactic acid, the general process is oxidation but oxygen
is never involved.

When oxygen is present, pyruvate is the final product. When

oxygen is absent, pyruvate remains inside the cytoplasm
where it can become very reactive. So there is something
that stabilizes it, which must be converted to lactic acid
because it is more s table than pyruvate.

A. Phases of Glycolysis

 Chemical Priming Phase/ Preparatory

Phase/Initial Preparative Phase / Energy
Investment Phase
 Phosphorylated forms of intermediates are
synthesized at the expense of ATP.
 requires 2 moles of ATP
 Includes the first 5 reactions
 Energy Yielding Phase/ ATP Generating Phase /
Energy Generation Phase
 Yields a total of 4 mol of ATP and 2 NADH
by substrate level phosphorylation per glucose
molecule metabolized at aerobic phase
 Initial Priming Phase: Modify the position of the
double bond - in glucose, the keto-group is terminal so
it is inputted in the beta carbon, the ultimate carbon.
If double bond is put in the middle, it creates “bond
strain” already. Then the other energy inputthere is
the conversion of fructose 6-phosphate to fructose
1,6-biphosphate. So when there is a creation of “bond
strain” we add another phosphate, meaning when
bond strain is created and put more bond strain, it is
easier to split it. When we split it, there will have both
by-products with the phosphate component.
 TAKE NOTE OF THE ENZYMES!
- Fructose is more unstable than glucose.
- This is the first phase of glycolysis (picture
above)
- If glycolysis happens in the LIVER, enzyme
responsible is HEXOKINASE
- If in the MUSCLE, GLUCOKINASE
- The importance of isomerism of glucose to
fructose is that fructose is easier to split than
glucose because it is more unstable thus less
energy to chop it down
- Interconverting process by enzyme
triosephosphateisomerase.If there is in
need for more energy, pathway is towards
dihydroxyacetone phosphate, if it is to be
stored (e.g. to triglyceride) the pathway shifts
to glyceraldehyde-3-phosphate depending on
the predominant need of the body.

 First liberation of ATP is at the conversion of 1,3-

biphosphoglycerate to 3-phosphoglycerate.
 Phosphoenolpyruvate has the greatest energy content.

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IV.Reactions of Glycolysis : Preparative
 All of the enzymes of glycolysis are found in the cytosol
 Phosphorylated sugar molecules do not readily
penetrate cell membranes:
o no specific transmembrane carriers
o too polar to diffuse through the lipid core of
membranes
A. Phosphorylation of Glucose
o Glucose: enters glycolysis by phosphorylation to
Glucose-6-phosphate
 Catalyzed by hexokinase
 Using ATP as phosphate donor
o Irreversible reaction: traps the sugar as cytosolic
glucose-6-phosphate
o Inhibited allosterically by its product G-6-P
B. Isomerization of Glucose-6-Phosphate
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Hexokinase IV (Glucokinase)
 Predominant enzyme (for glucose
phosphorylation) in liver parenchymal cells
(hepatocytes) and B cells of the pancreas;
Dominant in muscles
 Glucose sensor: threshold for insulin secretion
o Post prandial buffer system: removes
glucose from blood following a meal
 Higher Km: low affinity (requires higher glucose
concentration for half-saturation; not activated
at low sugar levels)
 Closely related to GLUT4
 Starvation (ensures brain viability)
 Not allosterically inhibited by G6PD (ensures
storage in liver)
Galactokinase: Phosphorylates galactose
Fructokinase: Phosphorylates fructose
o Aldose-ketose isomerization
o G-6-P is converted to fructose 6-phosphate (F-6-P)
 By phosphohexose isomerase (phosphoglucose
isomerase)
o Readily reversible at normal cellular concentrations of
the two hexose phosphates and thus catalyze
interconversion during glycolytic carbon flow during
gluconeogenesis
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 If an arrow is put in the bidirectional reaction with same
concentration of substrates, the net direction of the CHECKPOINT!
arrow is skewed in favor of fructose by 60/40
o e.g. Glucose concentration: 60%, Identification:
Fructose concentration: 40% = bidirectional 1. Phase of glycolysis where the phosphorylated
o ↑ Glucose: towards fructose forms of intermediates are synthesized at the
o ↑ Fructose: towards glucose expense of ATP
2. Enzyme that converts 1,3-BPG to 3-
Bi-directional arrow: phosphoglycerate
Depending on which one has a higher concentration, 3. Process that yelds 38 mol of ATP under
then the arrow will proceed (either way). The enzyme is aerobic conditions
“triosephosphate isomerase”. 4. Type of reaction where there is removal of
hydrogen making it more oxygen containing
2 GOALS OF THE REACTION: than hydrogen containing
a. to convert a molecule to a less stable molecule 5. The glycolytic pathways occurs in the
b. to change position of certain functional group cytoplasm while the TCA occurs in the
(aldehyde to keto group) mitochondria.
o The addition of more molecules creates a bond 6. The glycolytic pathways occurs in the occurs
strain creating a more unstable environment in the cytoplasm only.
7. Product of aerobic glycolysis (pyruvate)
ADDITIONAL NOTES TO REMEMBER: 8. Product of anaerobic glycolysis (lactate)
 Hexokinase = non-specific 9. Principal route for glucose metabolism and
 Glucokinase = specific for glucose major pathway for the metabolism of
 glucokinase that is found in hepatocytes has fructose, galactose, and other carbohydrates
a middle affinity for glucose comparing it derived from diet. (Glycolysis)
with the glucokinase found in the skeletal
muscles, comparing it with the glucokinase True or False:
found in the brain, it has a very low affinity 10. Glycolysis can function aerobically (product:
or high Km lactate) or anaerobically (product: pyruvate)
 the different types have a varying degree of 11. Higher Km has lower affinity
affinity (glucokinase), that is why there is a 12. Fructose 2,6-bisphosphate (F 2,6-BP) is the
preferential direction of absorption of most potent inhibitor of PFK-1
glucose in the bloodstream 13. Phosphorylation of fructose 6-phosphate (F
6-P) coverted to fructose 1,6-biphosphate (F
1,6-BP) with the utilization of the first ATP
14. Enzymes of glycolysis are found in the
cytosol and mitochondria
15. Two molecules of ATP are generated for each
molecule of glucose converted to two
moelcules of lactate
ANSWERS! 16. All processes in glycolysis, happen in the
1. Initial Preparative Phase cytoplasm.
2. Phosphoglycerate Kinase 17. Hexokinase III is the predominant enzyme
3. Oxidative Decarboxylation of Pyruvate (for glucose phosphorylation) in liver
4. Dehdyrogenase Reaction parenchymal cells (hepatocytes) and B cells
5. Aerobic Glycolysis
of the pancreas.
6. Anaerobic Glycolysis
7. Pyruvate
8. Lactate
9. Glycolysis
10. False (Interchanged)
11. True
12. False (Activator)
“Push yourself because, no one is going
13. False (Second ATP) to do it for you.”
14. False (Cytosol only)
15. True
16. True
17. False (Hexokinase IV)

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