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Transcript
Glycolysis
Goal: use 6 carbon compounds to produce _____________________
__________________________________________________
Remember 1st law of thermodynamics:
Matter (energy) can be ___________________________________
Energy in C-C bonds of glucose is transferred ___________________
Specifically: The break down of _________________ into _________________
Oxidative process
accompanied by the
reduction of NAD+
Glycolysis Energy Production:
-  __________ ATP
-  __________ ATP
-  __________ ATP
- 10 separate enzymatic reactions
to produce pyruvate from glucose
-  we will study each reaction in detail.
-  you must know:
- each enzyme, name & order
- order and structure of each
metabolite
What is fate of Pyruvate?
1
Glycolysis
Fate of pyruvate:
Aerobic (presence of O2)
- citric acid cycle breaks down
pyruvate ________________
- reduces ________________
_______________________
- next lecture series
Anaerobic (lack of O2)
1. Fermentation: loss of CO2
and _______________
2. Anaerobic glycolysis:
reduction of pyruvate
to lactate
- this lecture series
2
Glycolysis
History
Louis Pasteur 1822 - 1895
- French Scientist
- Inventor of pasteurization:
heating of liquids to kill harmful
organisms
- sponsored by French wine
industry to study fermentation
- determined in 1860 that glucose
supplied more energy in
presence of O2
3
Glycolysis
History
a.k.a.: Embden - Meyerhof Pathway
Otto Fritz Meyerhof
Gustav Georg Embden
1884 - 1951
1874 - 1933
German born biochemist
- German born biochemist
- University of Kiel
- between 1912 and 1918
determined the intermediates
of glycolysis
- awarded Nobel prize in
physiology or medicine, 1922
- Worked out precise steps
involved in the breakdown
of glucose
- Not included on
Nobel prize
4
Glycolysis
Two phases or parts to glycolysis
(10 steps between both phases)
Phase 1: - 2 “
” of
phosphorylating glucose
twice.
- forms fructose 1,6,-bisphosphate
- split into two molecules of
glyceraldehyde-3-phosphate
- ______________
Phase 2: - conversion of
glyceraldehyde-3-phosphate to
_________________
- coupled formation _________
- _________________
5
Glycolysis
Structure of Sugars, Chapter 16
a.k.a. carbohydrates, saccharides, sugars: simple organic compounds
that are ________________________________________________
- Can range in carbon number from 3 (simplest) to 4, 5, 6, and 7 (most complex)
Simplest 3 carbon sugars
- Exist as an aldehyde or ketone
6
Glycolysis
Structure of Sugars, Chapter 16
Sugars have ____________________________
___________________ used in glycolysis
7
Glycolysis
Structure of Sugars, Chapter 16
Numbering of carbons in sugars is based
on _____________________________.
- the most oxidized _________
_______________________
In ketone sugars the _______________
__________________
8
Glycolysis
Structure of Sugars, Chapter 16
5 or 6 carbon sugars normally exist ___________________
The free electrons on OH of C-5 bond with ________________
forming cyclic structure
Cyclic structure is similar to pyran: a six member ring with 5 carbons
and one oxygen
Can produce α
and β forms called
anomers
9
Glycolysis
Structure of Sugars, Chapter 16
Different representations of sugar structures
Fischer projections - _______________________ stereochemistry
of 3-D molecule
Haworth projections - a perspective representation of the _______
____________________________
Fischer
linear
cyclized
10
Glycolysis
Structure of Sugars, Chapter 16
Hermann Emil Fischer
Walter Haworth
1852 - 1919
1883 - 1950
-  German organic chemist
-  British organic chemist
-  worked at University of Berlin
-  worked at St. Andrews University
-  determined the structure and
stereochemistry of sugars between
1884 and 1894
-  worked on structure of
polysaccharides starting in 1915
- Nobel Prize in Chemistry, 1902
- Nobel Prize in Chemistry, 1937
11
Glycolysis
Phase 1
Step 1 - phosphorylation of glucose
producing _________________
____________________
- reaction carried out by the enzyme
- requires
- phosphorylation of glucose with out
ATP has ΔG = _______________
- coupled to ATP hydrolysis to give
reaction ΔG = _______________
12
Glycolysis
Phase 1
Step 1 - Glucose-6-phosphate (G6P) formation
Hexokinase
Remember : kinase is an enzyme that transfers a phosphate from ATP to substrate
Hexokinase undergoes large _______________________________
_____________________________
Glucose becomes almost __________________________________________
Glucose not bound
Glucose bound
This is an example of
what kind of enzymesubstrate interaction?
_____________
13
Glycolysis
Phase 1
Step 2 - G6P is isomerized to
- reaction carried out by the enzyme
- ring structure is broken producing
aldehyde at C-1 which is then
_________________________
- C-2 OH is oxidized to give ketone,
ring is closed connecting ______
_________________
- no net oxidation or reduction
14
Glycolysis
Phase 1
Step 3 - Fructose-6-phosphate (F6P) is
phosphorylated to give ________
________________________
- reaction carried out by the enzyme
- requires ______________
- phosphorylation of F6P with out
ATP has ΔG > 0
- coupled to ATP hydrolysis to give
reaction ΔG = -3.4 kcal/mole
15
Glycolysis
Phase 1
Step 3 - Fructose-1,6-bisphosphate formation
Phosphofructokinase (PFK)
- Both G6P and F6P can be utilized by
Do not have to
.
- Once PFK produces fructose-1,6-bisphosphate
it is
. It must go
- reaction carried out by PFK is not reversible
- PFK is key regulatory enzyme in glycolysis pathway
16
Glycolysis
Phase 1
Step 3 - Fructose-1,6-bisphosphate formation
Phosphofructokinase (PFK)
ATP is an allosteric regulator of PFK
In the presence of low [ATP]
In the presence of high [ATP]
Reasoning?
High cellular [ATP]
- no need for __________________
- PFK inactivated, _______________
___________
Low cellular [ATP]
- requirement for _______________
- PFK activated, ________________
17
Glycolysis
Phase 1
Step 4 - Fructose-1,6-bisphosphate is split
into two 3-carbon molecules:
________________________________
and _____________________________
- reaction carried out by the enzyme
- intermediates no
- DHAP and GA3P
18
Glycolysis
Phase 1
Step 5 - DHAP is converted to
- reaction carried out by the enzyme
- reaction produces a second
- now 6 carbon glucose has been
19
Glycolysis
Phase 2 - two molecules of each intermediate take part in each reaction
Step 6 - GA3P is oxidized to
- reaction carried out by the enzyme
- involves oxidation of GA3P, NAD+
as e- acceptor, and phosphorylation
at C-1
- Phosphate comes not from ATP
but from inorganic phosphate:
20
Glycolysis
Phase 2
Step 6 - GA3P is oxidized to 1,3-bisphosphoglycerate
Takes place in a two step reaction
1. GA3P is oxidized to 3-phosphoglycerate
- aldehyde is oxidized
21
Glycolysis
Phase 2
Step 6 - GA3P is oxidized to 1,3-bisphosphoglycerate
Takes place in a two step reaction
2. 3-phosphoglycerate is phosphorylated by Pi
This reaction has ΔG
, but overall ΔG
22
Glycolysis
Phase 2
Step 7 - 1,3-bisphosphoglycerate is
dephosphorylated to produce ATP
- reaction carried out by the enzyme
- two ATP are produced per
- thus two ATP used in Phase 1
- substrate level phosphorylationATP production by the
direct transfer of phosphate from
intermediate ___________________
_____________________________23
Glycolysis
Phase 2
Step 8 - 3-phosphoglycerate is converted
to
- reaction carried out by the enzyme
- this reaction takes place to set up
next reaction
24
Glycolysis
Phase 2
Step 9 - 2-phosphoglycerate loses H2O
to produce
- reaction carried out by the enzyme
- e- transfer is not involved
- requires Mg2+ which binds H2O
for elimination
25
Glycolysis
Phase 2
Step 10 - phosphoenolpyruvate is
dephosphorylated to form ATP
from ADP, producing
- reaction carried out by the enzyme
- two ATP are produced per glucose
molecule, substrate level phosphor.
- pyruvate kinase is allosterically
regulated by
- inhibited by high levels
26
Glycolysis
Regulation points of glycolysis
1.  ___________________
Glucose-6-phosphate production
2. ____________________
Fructose 1,6-bisphosphate production
inhibited by ATP
3. _____________
pyruvate produced
inhibited by ATP
27
Glycolysis
What is the energy production
of glycolysis?
2 ATP used in phase 1
- ________________
- ________________
4 ATP produce in phase 2
- __________________
- __________________
Overall ATP production:
__________
28
Glycolysis
What is the fate of pyruvate?
Depends on the ___________________
__________ conditions:
- pyruvate enters citric acid cycle
(TCA cycle), ______________ to
generate reducing agents for ATP
production (next lecture series)
_____________ conditions:
1. Anaerobic glycolysis, the production
of ____________________. Occurs
in muscles
2. Alcohol fermentation, production
of ethanol from pyruvate
29
Glycolysis
Anaerobic Glycolysis
- Pyruvate is reduced to lactate
- occurs in
- only form of glycolysis
- catalyzed by enzyme
- oxidizes NADH to NAD+
reduction
30
Glycolysis
Anaerobic Glycolysis
Why carry out anaerobic glycolysis?
- citric acid cycle (TCA cycle) requires
.
- but during anaerobic conditions
- lactate dehydrogenase produces
- this NAD+ can then be used by
_________________________
_________________________
-  only place in glycolysis NAD+
required, thus glycolysis can
continue and produce __________
____________________________
31
Glycolysis
Alcoholic Fermentation
2 steps in the production of ethanol from pyruvate
1. The enzyme
produce acetaldehyde
removes CO2 from pyruvate to
32
Glycolysis
Alcoholic Fermentation
2 steps in the production of ethanol from pyruvate
2. The enzyme
ethanol
reduces acetaldehyde to
Produces NAD+ that can then be used by glyeraldehyde-3-phosphate
dehydrogenase
reduction
2H+ + 2e-
NAD+
NADH
33
Glycolysis
Alcoholic Fermentation
Beer making
Extract sugars from
malted barley
in water
yeast
Aerobic
glycolysis
Anaerobic
fermentation
CO2
CO2
Place in air tight
bottle, yeast produced
CO2 carbonates beer
Use of O2
EtOH
EtOH
EtOH
EtOH
EtOH
Air tight container with
exhaust for gas
34