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Glycolysis

Glycolysis (sugar
(sugar--breaking)
series of ten reactions
breaks down glucose into 2 pyruvic acids
occurs in cytosol
anaerobic phase of cellular respiration
yields two ATP molecules per glucose
Summarized by three main events
1. phosphorylation
2. splitting
3. production of NADH and ATP

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Overall Process

Glycolysis

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Glycolysis

Glycolysis

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Glycolysis

Glycolysis

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Net Result of Glycolysis

Glucose + 2 ATP 2 NADH + 4 ATP + 2 pyruvate

Net energy outcome 2 NADH and 2 ATP

What to Know About Glycolysis

10 enzymes / 5 reaction types

Kinases add a phosphate group to intermediates,
phosphate transfer
Isomerases rearranges the atoms in the
intermediates
Dehydrogenase causes a redox reaction, electron
ends up on FADH2 or NADH
Dehydrations removal of H2O

Cleavage reaction split glucose to 2 3-C molecules

Net outcome of glycolysis

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Steps and Reactions

Step 1 kinase, phosphate transfer
Step 2 isomerase, rearrange atoms
Step 3 kinase, phosphate transfer
Step 4 cleavage to 2 3-C molecules
Step 5 isomerase, rearrange atoms
Step 6 dehydrogenase, make NADH
Step 7 kinase, phosphate transfer
Step 8 isomerase, rearrange atoms
Step 9 removal of H2O
Step 10 kinase, phosphate transfer

CH2O
C
6

H
4

HO

CH2OH

Dihydroxyacetone
phosphate

OH

OH

OH

CH2O

C O

OH2C

HO

2 NADH + 2H+

HCOH

ADP

O
OH

Glucose 6-phosphate

OH
2

ATP

CH2O

OH

1, 3-Bisphosphoglyceric
acid (2 molecules)

2 ADP

2 NAD+ + 2 P

Glucose (1 molecule)

ATP
1

CH2O

Glyceraldehyde 3-phosphate

HCOH

CH2OH

H
C O

HCOH

3-Phosphoglyceric acid
(2 molecules)

COOH
8

OH2C 6

HO

HCO

Phosphofructokinase
OH2C

H
3

OH

9
O

COOH
CH2O

HO

2-Phosphoglyceric acid
(2 molecules)

CH2
C

ADP

Fructose 6-phosphate

ATP

COOH

OH

OH

CH2OH
2

H
4

CH2OH

OH

Fructose 1, 6-bisphosphate

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CH3
C O
COOH

Phosphoenolpyruvic acid
(2 molecules)

2 ADP

2 ATP

Pyruvic acid
(2 molecules)

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Fates of Pyruvate
Pyruvate is most commonly metabolized in

one of three ways, depending on the type of

organism and the presence or absence of O2.

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aerobic conditions
plants and animals

Acetyl CoA 13

Citric acid cycle

OH
O
- 11 anaerobic conditions
CH3 CHCOOCH3 CCOO
contracting muscle
Lactate
Pyruvate
10 anaerobic conditions
CH3 CH2 OH + CO2
fermentation in yeast
Ethanol

Regulation of Glycolysis
Enzyme

Activator

Hexokinase
(Step 1)

Inhibitor
Glucose-6Phosphate, ATP

PFK
(Step 3)

Fructose-2,6-bis
phosphate, AMP

Citrate, ATP

Pyruvate
kinase
(Step 10)

Fructose-1,6-bis
phosphate, AMP

Acetyl-CoA, ATP

All the above enzymes are allosteric

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Krebs Cycle
(Citric Acid Cycle)
Cycle)

The Krebs Cycle

Also known as citric acid cycle

Occurs in matrix of mitochondria
Series of redox reactions
2 decarboxylation reactions release CO2
Reduced coenzymes (NADH and FADH2)
are the most important outcome
One molecule of ATP generated by
substrate-level phosphorylation

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The Krebs Cycle

The Krebs Cycle (steps)

Step 1: condensation of acetyl CoA with oxaloacetate:

The high-energy thioester of acetyl CoA is
hydrolyzed.
This hydrolysis provides the energy to drive Step 1.
O
CH3 C-SCoA
Acetyl-CoA
+

O C-COO
CH2 -COO

citrate
s yn th ase

CH2 -COOHO C-COOCH2 -COO-

CoA-SH
Coenzyme A

Citrate

Oxaloacetate
Citrate synthase, an allosteric enzyme, is inhibited by
NADH, ATP, and succinyl-CoA.

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Step 2: dehydration and rehydration, catalyzed by

aconitase, gives isocitrate.
CH2 -COO CH2 -COO - H2 O
HO C-COO C-COO CH2 -COO Citrate

CH- COO -

H2 O
Aconitase

Aconitate

CH2 -COO H C-COO HO CH- COO Isocitrate

> Citrate and aconitate are achiral; neither has a

stereocenter.
> Isocitrate is chiral; it has 2 stereocenters and 4
stereoisomers are possible.
> Only one of the 4 possible stereoisomers is
formed in the cycle.

Step 3: oxidation of isocitrate followed by

decarboxylation gives a-ketoglutarate.

CoA -SH
CH2 -COO CH2
O C-COO -Ketoglutarate

N AD +

N AD H

-ketoglutarate
dehydrogenase
complex

CH2 -COO CH2

+ CO 2

O C SCoA
S uccinyl-CoA

The two carbons of the acetyl group of acetyl CoA

are still present in succinyl CoA.
This multienzyme complex is inhibited by ATP,
NADH, and succinyl CoA; it is activated by ADP and
NAD+.

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Step 5: formation of succinate.

CoA-SH
N AD +

CH2 -COO CH2

NADH

CH2 -COO CH2

-ketoglutarate
dehydrogenase
complex

O C-COO -Ketoglutarate

+ CO 2

O C SCoA
Succinyl-CoA

The two CH2-COO- groups of succinate are now

equivalent.
This is the first, and only, energy-yielding step of the
cycle; a molecule of GTP is produced.

Step 6: oxidation of succinate to fumarate.

CH2 -COO

FAD

CH2 -COO -

succinate
dehydrogenase

S uccinate

FAD H2
-

OOC

C
C

COOH

Fumarate

Step 7: hydration of fumarate to L-malate.

H
-

C
C

COO-

OOC
H
Fumarate

H2 O HO CH- COO
CH2 -COO fumarase

L-Malate

Malate is chiral and can exist as a pair of enantiomers;

It is produced in the cycle as a single stereoisomer.

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Step 8: Oxidation of Malate.

HO CH- COO CH2 -COO L-Malate

N AD + N AD H
malate
dehydrogenase

O C-COO

CH2 -COO Oxaloacetate

Oxaloacetate now can react with acetyl CoA

to start another round of the cycle by
repeating Step 1.

Summary of Krebs Cycle Steps and Reactions

Step 1 add acetyl CoA to oxaloacetate, citrate (6 C)

Step 2 isomerase, rearrange atoms (6 C)

Step 3 dehydrogenase, make NADH, lose CO2 (5 C)

Step 4 dehydrogenase, make NADH, lose CO2, add CoA

back to molecule (4 C)

Step 5 generate GTP, remove CoA (4 C)

Step 6 dehydrogenase, make FADH2, rearrange atoms (4 C)

Step 7 add H2O (4 C)

Step 8 dehydrogenase, make NADH, regenerates

oxaloacetate (4 C)

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The Krebs Cycle

Cycle repeats as long as pyruvic acid and
oxygen are available
for each citric acid molecule:
one ATP is produced
eight hydrogen atoms are transferred to
NAD+ and FAD
two CO2 produced

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Oxidation of each NADH gives 2.5 (or 3) ATP.

Oxidation of each FADH2 gives 1.5 (or 2) ATP.

Electron Transport
Chain

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Electron transport chain

Series of electron carriers in inner

mitochondrial membrane reduced and
oxidized
As electrons pass through chain, exergonic
reactions release energy used to form ATP
Chemiosmosis
Final electron acceptor is oxygen to form
water

Electron transport chain

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Chemiosmosis
Carriers act as proton pumps to expel H+
from mitochondrial matrix
Creates H+ electrochemical gradient
concentration gradient and electrical gradient
Gradient has potential energy proton
motive force
As H+ flows back into matrix through
membrane, generates ATP using ATP
synthase

Outer membrane
Inner membrane
Matrix
H+

High
concentration
between inner and
outer mitochondrial
membranes

Inner
mitochondrial
membrane

H+
channel
2 H+

H+

Electron
transport
chain
(includes
proton pumps)

1 Energy from
NADH + H+

ADP +

Low H+ concentration in
matrix of mitochondrion

ATP synthase

ATP

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Electron--Transport Chain
Electron

Final step in energy generation most energy

released here
e- of NADH and FADH2 move through the chain,
moving to lower energy level
Occurs in the inner membrane of the
mitochondria
Specialized molecules accept and donate e- as
they move down chain
Create an electrochemical gradient
As e- move down chain, H+ move across the
membrane, altering the concentration of H+ on either
side = gradient
Gradient used to generate ATP

The actions of the three proton pumps and ATP

synthase in the inner membrane of mitochondria
Space between outer
and inner mitochondrial
membranes

H+ channel
H+

H+

H+

Cyt c
Inner
mitochondrial
membrane

e
Q

e
e

e
Mitochondrial
matrix

1 1/2 O2
+ H+
NADH

NAD

H+

ADP +P
3 H2O

2
NADH dehydrogenase
complex: FMN and
five Fe-S centers

3
Cytochrome b-c1
complex: cyt b, cyt c1,
and an Fe-S center

ATP synthase

ATP

Cytochrome oxidase
complex: cyt a,
cyt a3,and two Cu

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Summary of cellular respiration

Copyright 2009, John Wiley & Sons, Inc.

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