Generation of ATP from Glucose

ILOs:
1- List and discuss reaction steps of glycolysis.

2- Define aerobic & anaerobic types of glycolysis & list the importance of
each type & the differences between both.

3- Describe regulation of glycolysis.

Glycolysis
It means breakdown of glucose into 2 molecules of pyruvate aerobically (in
the presence O 2) or 2 molecules of lactate an aerobically (in the absence of
O2).
Site: (cytoplasm of all tissue cells).
It is of physiological importance in tissues of no mitochondria as mature
RBCs.
Specific tissue functions of glycolysis:
RBC’s

They depend only upon glycolysis for energy production.

Skeletal muscle
Source of energy during exercise particularly high intensity exercise.
Adipose tissue

Source of glycerol-P for TG synthesis

Source of acetyl-CoA for FA synthesis.
Liver
Source of acetyl-CoA for FA synthesis
Source of glycerol-P for TG synthesis
Stages of glycolysis:
1. Stage one (the energy requiring stage):
a) One molecule of glucose is converted into two molecules of
glyceraldehyde-3-phosphate.

b) These steps require 2 molecules of ATP (energy loss)

2. Stage two (the energy producing stage):
a) The 2 molecules of glyceraldehyde-3-phosphate are converted into 2
pyruvate molecules (aerobic glycolysis) or 2 lactate molecules (anaerobic
glycolysis).

b) These steps produce ATP molecules (energy production).

 glucose Glycolysis
ATP
Hexokinase
ADP
glucose-6-phosphate
Phosphoglucose Isomerase
fructose-6-phosphate
ATP
Phosphofructokinase
ADP
fructose-1,6-bisphosphate
Aldolase

glyceraldehyde-3-phosphate + dihydroxyacetone-phosphate
Triosephosphate
Isomerase
Glycolysis continued
 glyceraldehyde-3-phosphate
NAD+ + Pi Glyceraldehyde-3-phosphate
NADH + H+ Dehydrogenase
1,3-bisphosphoglycerate
ADP
Phosphoglycerate Kinase
ATP
3-phosphoglycerate
Phosphoglycerate Mutase
2-phosphoglycerate

H2O Enolase
phosphoenolpyruvate
ADP
Pyruvate Kinase
ATP
pyruvate
ATP yield in glycolysis
ATP production = ATP produced – ATP utilized
ATP produced ATP utilized Net energy
In absence of 4 ATP 2 ATP
oxygen
(Substrate level
(anaerobic
phosphorylation)
glycolysis) • From glucose to
glucose-6-p.
• 2ATP from 1,3 2 ATP
BPG.
• From fructose-6-
phosphate to
fructose 1,6
• 2ATP from
bisphosphate.
phosphoenol
pyruvate
In presence of 4 ATP (Substrate 2 ATP
oxygen (aerobic level
glycolysis) phosphorylation)
•From glucose to
glucose-6-
•2ATP from 1,3 phosphate.
BPG.
6 ATP
•From fructose-6-
• 2ATP from phosphate to Or
phosphoenol fructose t ,6 8 ATP
pyruvate bisphosphate.
+
4 ATP or 6 ATP
(From oxidation of 2
NADH + H in
mitochondria).
Differences between glucokinase and hexokinase

Glucokinase Hexokinase

Site Liver cells only All tissues

Substrate Glucose only Hexoses

Effect of insulin Stimulated No effect

Affinity Low (high K ) High (low K )

m m

Effect of glucose-
No effect Inhibited
6-phosphate

Glucose level Acts over 100 mg% Acts on low glucose level

Difference between Aerobic and Anerobic Glycolysis

Biological importance of Glycolysis
1- Energy production:
a- Anaerobic glycolysis gives 2 ATP.
b- Aerobic glycolysis gives 8 ATP.
2- Oxygenation of tissues:
Through formation of 2,3 bisphosphoglycerate which decreases the
affinity of hemoglobin to O 2
3- Provides important intermediates:
3 phosphoglcerate which gives amino acid serine.
4- Aerobic glycolysis provide the mitochondria with pyruvate which gives
acetyl CoA → Kreb’s cycle.

Pyruvate can be further processed:

a) Anaerobically to lactate in muscle, RBCs and in certain micro-organisms

b) Anaerobically to ethanol (fermentation)

c) Aerobically to CO2 and H2O via the citric acid cycle.

Fermentation:

-Anaerobic organisms lack a respiratory chain.

-They must reoxidize NADH produced in glycolysis through some other

reaction, because NAD+ is needed for the glyceraldehyde-3-phosphate
dehydrogenase reaction.

Glyceraldehyde-3-phosphate
Dehydrogenase
H O + H+ O OPO32−
1C NAD+ NADH 1C
+ Pi
H C OH H C OH
2 2
2− 2−
3 CH2OPO3 3 CH2OPO3

glyceraldehyde- 1,3-bisphospho-
3-phosphate glycerate

-Usually, NADH is reoxidized as pyruvate is converted to a more reduced

compound.

-The complete pathway, including glycolysis and the reoxidation of NADH,

is called fermentation
 Lactate Dehydrogenase
O O− O O−
C NADH + H+ NAD+ C
C O HC OH
CH3 CH3
pyruvate lactate
E.g., Lactate dehydrogenase catalyzes reduction of the keto in pyruvate to
a hydroxyl, yielding lactate, as NADH is oxidized to NAD +.

Lactate, in addition to being an end-product of fermentation, serves as a

mobile form of nutrient energy & possibly as a signal molecule in
mammalian organisms.

Cell membranes contain carrier proteins that facilitate transport of lactate.

Skeletal muscles ferment glucose to lactate during exercise when the

exertion is brief and intense. Lactate released to the blood may be taken up
by other tissues or by skeletal muscle after exercise and converted via lactate
dehydrogenase back to pyruvate which may be oxidized in Krebs cycle or
(in liver) converted back to glucose via gluconeogenesis.

Lactate serves as a fuel source for cardiac muscle as well as brain neurons.

Astrocytes which surround and protect neurons in the brain ferment glucose
to lactate and release it. Lactate taken up by adjacent neurons is converted to
pyruvate that is oxidized via Krebs cycle.
 Pyruvate Alcohol
Decarboxylase Dehydrogenase
O O−
CO2 H NADH + H+ NAD+ H
C O
C O C H C OH

CH3 CH3 CH3

pyruvate acetaldehyde ethanol

Some anaerobic organisms metabolize pyruvate to ethanol which is excreted

as a waste product.

NADH is converted to NAD+ in the reaction catalyzed by alcohol

dehydrogenase.

Pyruvate carboxylation, decarboxylation shares in carbohydrate

metabolism
Regulation of Glycolysis
The rate of glycolysis is regulated by the control of the 3 irreversible
enzymes (key enzymes) these enzymes are

Glucokinase or hexokinase, phosphofructokinase 1 and pyruvate kinase

1- Hormonal regulation:

a- Insulin stimulates the biosynthesis of the last three enzymes →

stimulating glycolysis.

b- Adrenaline and glucagon → inhibit pyruvate kinase → inhibiting

glycolysis.
2- Effect of substrates:

a- Glucose-6-phosphate inhibits hexokinase (not glucokinase).

b- Citrate inhibits phosphfructokinase 1.

3- Role of energy in regulation:

a- High levels of ADP, AMP means low energy concentration in the cells, so
stimulate phosphfructokinase1.

b- High levels of ATP mean high energy so it inhibits phosphfructokinase 1,

pyruvate kinase and glycolysis.

Sources of lactate:
Cori cycle

Muscle Blood Liver

Glucose Glucose Glucose

2ATP Glycolysis Gluconeogenesis

6 ATP
Lactic acid Lactic acid Lactic acid

Muscle fatigue Kidney excretion

-Skeletal muscles ferment glucose to lactate during exercise when the

exertion is brief and intense.
-Astrocytes which surround and protect neurons in the brain ferment glucose
to lactate and release it.

-RBCs since no way to regenerate NAD except by reducing pyruvate into

lactate by LDH (no mitochondria in RBCs).

-Lactate in addition to being an end-product of fermentation serves as a

mobile form of nutrient energy. Cell membranes contain carrier proteins that
facilitate transport of lactate.

-Lactate released to the blood may be taken up by other tissues or by skeletal

muscle after exercise and converted by LDH back into pyruvate which may
be oxidized in Krebs cycle or converted back to glucose via gluconeogenesis
in the liver.