What is metabolism?

Definition: Metabolism is the sum total

of the chemical reactions of
biomolecules in an organism
Metabolism consists of
1. catabolism: the breakdown of larger
molecules into smaller ones; an oxidative
process that releases energy
2. anabolism: the synthesis of larger
molecules from smaller ones; a reductive
process that requires energy
Catabolism: the oxidative breakdown of nutrients
Anabolism: the reductive synthesis of biomolecules

Eg.

Terminology of
light
metabolism
6 CO + 6 H O C H O
+6O
2(g)

Anabolism

(l)

12

6(aq)

2(g)

photosynthesis

C6H12O6 (aq) + 6O2 (g) 6CO2 (g) + 6H2O

Catabolism

respiration

Metabolic pathway: A sequence of reactions, where

the product of one reaction becomes the substrate for
the next reaction.
- either linear pathway or cyclic pathway
- metabolic pathways proceed in many stages, allowing for efficient
use of energy

Metabolites: intermediates in metabolic pathway

Metabolic pathways

Metabolic pathway: Linear or cyclic

Comparison of anabolism and

Metabolismcatabolism
is the sum total of the
chemical reactions of biomolecules in
an organism

Metabolism
Metabolism involves the energy flow in the cell
Photoautotroph via photosynthesis transfers
the energy to heterotrophs
Heterotrophs obtain
the energy through
oxidation/reduction of
organic compounds
(carbohydrate, lipid and
proteins)
Food supplies the energy
Energy = ATP

The role of oxidation and reduction in metabolism

Oxidation-Reduction (redox) reactions are those in

which electrons are transferred from a donor to an
acceptor

oxidation: the loss of electrons; the

substance that loses the electrons is
called a reducing agent
reduction: the gain of electrons; the
substance that gains the electrons is
called an oxidizing agent
Reducedin most reduced form- alkane
Carbon
Oxidized
Carbon
in most oxidized form- CO2 (final product of
catabolism)

Oxidation and reduction in metabolism

Oxidation of ethanol by NAD +
NAD + + H+ + 2eOxidizing agent
e acceptor

CH3 CH2 OH

reducing agent e donor

CH3 CH2 OH + NAD +

Ethanol

Reduction of pyruvate by NADH

NADH
O
CH3 CCOO- + 2H+ + 2eO
CH3 CCOO- + NADH + H+
Pyruvate

Reduction gain e

NADH
O Oxidation less e
CH3 CH + 2H+ + 2eO
CH3 CH + NADH + H+

Acetaldehyde

NAD + + H+ + 2eOH
CH3 CHCOOOH
CH3 CHCOO- + NAD +
Lactate

Metabolism: features
Metabolic pathway:
1. Enzymes multienzymes
2. Coenzymes
3. ATP produced or used

Regulation of metabolic pathway:

. Feedback inhibition or
. Feed-forward activation
A group of noncovalently associated
enzymes that catalyze 2 or more
sequential steps in metabolic/biochemical
pathway

Metabolism: Regulation

Regulation of metabolic pathway:

1. Feedback inhibition = product (usually ultimate
product) of a pathway controls the rate of synthesis
through inhibition of an early step (usually the first step)
E1

E2

E3 E 4

E5

ABCDEP

2. Feed-forward activation = metabolite produced early

in pathway activates enzyme that catalyzes a reaction
further down the pathway
E1

ABCDEP

E2

E3

E4

E5

Coenzymes
Coenzymes in metabolism:
NAD+/NADH
NADP+/NADPH Electron carriers
FAD+/FADH2
Coenzyme A (CoASH) activation of
metabolites

NAD+/NADH: An Important Coenzyme

Nicotinamide adenine

dinucleotide (NAD+) is
an important
coenzyme
Acts as a biological
oxidizing agent
The structure of
NAD+/NADH is
comprised of a
nicotinamide portion.
It is a derivative of
nicotinic acid
NAD+ is a two-electron
oxidizing agent, and is
reducedform,
to NADH
Reduced
NADH carries 2 electrons

NADP+/NADPH:
Also comprised of nicotinamide portion
Nicotinamide
adenine dinucleotide
phosphate (NADP+)
oxidizing agent
NADPH involves in
reductive
biosynthesis
Differ with NAD+ at
ribose (C2 contain a
phosphoryl group,
PO32-

Reduced form,
NADPH carries 2

As electron carrier in
photosythesis and
pentose phosphate
Anabolis
pathway

The Structures Flavin Adenine

Dinucleotide (FAD)
FAD is also a
biological
oxidizing
agent
FAD can
accept oneelectron
The
terminal e or
acceptor
(O2) can
two-electron
accept only unpaired
e (e must be
transferred to O2 one
at a time)

FADH carries 1 electron, FADH2 carries 2 electrons

FAD/FADH2

FADH (semiquinone form) carries 1 electron,

FADH2 (fully reduced hydroquinone form) carries
2 electrons

Formation of fully reduced

hydroquinone form bypass the

Coenzyme A in Activation of
Metabolic Pathways
A step frequently encountered in
metabolism is activation
activation: the formation of a more
reactive substance
A metabolite is bonded to some other
molecule and the free-energy change for
breaking the new bond is negative.
Causes next reaction to be exergonic

Coenzyme A (CoASH)
Coenzyme A
functions as a
carrier of acetyl and
other acyl groups
Has sulfhydryl/thiol
group Thioester
bond

Acetyl-CoA: is a high-energy
compound because of the
presence of thioester bond
hydrolysis will release energy

ATP- high energy compound

ATP is essential high
energy bondcontaining
compound
Phosphorylation of
ADP to ATP requires
energy
Hydrolysis of ATP to
ADP releases energy

nucleotide

Phosphorylation: the addition of phosphoryl (PO32-) group/Pi

(inorganic phosphate)

The Phosphoric Anhydride Bonds

in ATP are High Energy Bonds
High Energy
bondsbonds that require
or release
convenient
amounts of energy,
depending on the
direction of the
reaction
Couple reactions:
the energy
released by one
reaction, such as
ATP hydrolysis,

Couple reaction: example

Role of ATP as Energy

Currency
Phosphorylation
of ADP requires
energy from
breakdown of
nutrients
The energy from
(catabolism)
hydrolysis of ATP
will be used in
the formation of
products
(anabolism)

Metabolism of
Carbohydrate

Major pathways of
carbohydrate metabolism

Metabolism (2)

Glycolysis
Glycolysis is the first stage of
glucose metabolism
Glycolysis converts 1 molecule of
glucose to 2 units of pyruvate
(three C units) and the process
involves the synthesis of ATP and
reduction of NAD+ (to NADH)
The pathway has 10
steps/reactions
Glycolysis are divided into 2
stages/phases,

Phase 1=1st 5 reactions

Phase 2=2nd 5
reactions
Linear
pathway

Glycolysis

Glycolysisaredividedinto2stages/phases,
1. Phase1=1st5reactions
. Energyinvestment
. Ahexosesugar(glucose)issplitinto
2moleculesofthreeCmetabolite
(glyceraldehyde3phosphate=GAP).The
processconsume2ATP
2. Phase2=2nd5reactions
. Energyrecovery
. ThetwomoleculesofGAPareconvertedto
2moleculesofpyruvatewiththegeneration
of4ATPand2NADH.
Overallequation
Glucose+2NAD++2ADP+2Pi
2pyruvate+2NADH+2ATP+2H2O+4H+
Glycolysishasanetprofitof2ATPperglucose

The reaction of
glycolysis
1. Phosphorylation of glucose
to give glucose-6-phosphate
2. Isomerization of glucose-6phosphate to give fructose6-phosphate
3. Phosphorylation of
fructose-6-phosphate to yield
fructose-1,6-biphosphate
4. Cleavage of fructose-1,6,bisphosphate to give
glyceraldehyde-3-phosphate
and dihydroxyacetone
phosphate
5. Isomerization of
dihydroxyacetone phosphate
to give glyceraldehyde-3-

glucokinase
1
Use ATP

Use ATP
3
phosphofructokinase

4
5

The reaction of glycolysis

(cont)
6

Glyceraldehyde-3-P
dehydrogenase

Electron acceptor
NAD+
transfer
Phosphorylation of
ADP to ATP

isomerization

dehydration

1
0

transfer
Phosphorylation of
ADP to ATP

6. Oxidation of
glyceraldehyde-3phosphate to give 1,3biphosphoglycerate
7. Transfer of a phosphate
group from 1,3biphosphoglycerate to ADP
to give 3-phosphoglycerate
8. Isomerization of 3phosphoglycerate to give
2-phosphoglycerate
9. Dehydration of 2phosphoglycerate to give
phosphoenolpyruvate
10.Transfer of a phosphate
group from
phosphoenolpyruvate to

Glycolysis
Dephosphorylation of ATP
By kinase enzyme at
Phosphorylation of ADP step 1, 3, 7 and 10
Oxidation of intermediates and
reduction of NAD+ to NADH by
dehydrogenase reactions
- step 6
- glyceraldehyde-3-phosphate
dehydrogenase

ATP production
ATP is produced by phosphorylation of ADP is through substrate-level
phosphorylation
Substrate-level phosphorylation the
process of forming ATP Glycolysis
by phosphoryl
- Step 7
group transfer from reactiveand 10
intermediates to ADP
1,3-bisphosphoglycerate and
phosphoenolpyruvate high-energy
intermediates/compounds
Oxidative phosphorylation the process of

Fates of Pyruvate From Glycolysis

Once pyruvate is
formed, it has one of
several fates
In aerobic metabolismpyruvate will enter the
citric acid cycle, end
product in aerobic
metabolism CO2 and H2O
In anaerobic
metabolism- the
pyruvate loses CO2
produce ethanol =
alcoholic fermentation
produce lactate =
anaerobic glycolysis

Anaerobic Metabolism of Pyruvate

Under anaerobic conditions, the most important
pathway for the regeneration of NAD+ is reduction of
pyruvate to lactate
Lactate dehydrogenase (LDH) is a tetrameric
isoenzyme consisting of H and M subunits; H4
predominates
heart muscle,
and M4 in skeletal
In inmuscle,
during
vigorous
exercise demand of ATP but
muscle
O is in short supply is largely
2

synthesized
via
anaerobic
glycolysis
which
rapidly
generates
ATP
rather
than
through
slower
oxidative
phosphorylation

Alcoholic Fermentation
In anaerobic

Two reactions lead to the production of ethanol:

bacteria

Decarboxylation of pyruvate
to acetaldehyde
Reduction of acetaldehyde
to ethanol
Pyruvate decarboxylase is the enzyme that catalyzes the first
reaction
This enzyme require Mg2+ and the cofactor, thiamine
pyrophosphate (TPP)
Alcohol dehydrogenase catalyzes the conversion of
acetaldehyde to ethanol

NAD+ Needs to be Recycled to Prevent

Decrease in Oxidation Reactions

Structure of cell

Cytopla
sm/Cyto
sol

TYPICAL PROKARYOTIC CELL

Where does the Glycolysis Take

Place?
Glycolysis is
universal!

Cytosol

Citric acid cycle

Requires aerobic condition
Amphibolic (both catabolic & anabolic)
Serves 2 purposes:
1. Oxidize Acetyl-CoA to CO2 to produce energy
(ATP & reducing power of NADH & FADH2)involved in the aerobic catabolism of
carbohydrates, lipids and amino acids
2. Supply precursors for biosynthesis of
carbohydrates, lipids, amino acids, nucleotides
and porphyrins

TCA
Circular pathway
Two-carbon unit
needed at the start
of the citric acid
cycle
The two-carbon unit
is acetyl-CoA
Involves 8 reactions
The overall reaction
from 1 acetyl-CoA
produce 3 NADH, 1
FADH2, 2 CO2 and 1
GTP (equivalent to
1 ATP)

Pyruvate is converted to
Acetyl-CoA activation of
pyruvate
Pyruvate dehydrogenase complex is

responsible for the conversion of

pyruvate to acetyl-CoA
Five enzymes in complex
Requires the presence of cofactors TPP
(thymine pyrophosphate), FAD, NAD+, and
lipoic acid and coenzyme A (CoA-SH)
Oxidation of pyruvate and
The overall reaction of the reduction
pyruvate
of NAD
3C
dehydrogenase complex is the conversion
Pyruvate
=
of pyruvate,
NAD+, and CoA-SH to acetyl2C
pyruvic acid
+
Thioester,
high energy
CoA, NADH + H
, and
CO2compound
+

Coenzyme A (CoASH)
Coenzyme A
functions as a
carrier of acetyl and
other acyl groups
Has sulfhydryl/thiol
group Thioester
bond

CoASH

Acetyl-CoA: is a highenergy compound because

of the presence of thioester
bond hydrolysis will release

Features of TCA
Electron acceptor
NAD+ and FAD

Circular pathway
Two-carbon unit needed
at the start of the citric
acid cycle
The two-carbon unit is
acetyl-CoA
Involves 8 reactions
The overall reaction from
1 acetyl-CoA produce 3
NADH, 1 FADH2, 2 CO2
and 1 GTP (equivalent
X2
to 1 ATP)
How about 1 molecule of glucose?

Mitochondrial
matrix

Citric acid cycle - features

Oxidation decarboxylation
- CO2 leaves at step 3 and 4
Oxidation of intermediates and
reduction of NAD+ to NADH by
dehydrogenase reactions
- step 3, 4 and 8
- isocitrate dehydrogenase
- -ketoglutarate dehydrogenase
- malate dehydrogenase
Oxidation of intermediates and
reduction of FAD+ to FADH2 by
succinate dehydrogenase reaction
- step 6
Phosphorylation of GDP to GTP
step 5

Where does the Citric Acid Cycle Take Place?

In eukaryotes, cycle takes place in the mitochondrial
matrix
In prokaryotes?

Cytoplasm

The Central Relationship of the

Citric Acid Cycle to Catabolism

TCA involves 8 series of reactions

that oxidizes the acetyl group of
acetyl-CoA to 2 molecules of CO2
and the energy is conserves in
NADH, FADH2 and high-energy
compound, GTPGuanosine Tri-Phosphate

Acetyl-CoA synthesize from

pyruvate (glycolysis product)

Aerobic catabolism

NADH, FADH2 from glycolysis and

TCA will enter the Electron
Transport Chain (ETC) to produce
more ATP (oxidative
phosphorylation)

1 NADH = 3 ATP,

In ETC

1 FADH2 = 2 ATP
ETC take place in mitochondria In prokaryotes?
inner membrane
(eukaryotes)
Plasma membrane

Oxidation of Pyruvate Forms CO2 and ATP

Aerobic metabolism is more efficient than anaerobic metabolism

Citric acid cycle - amphibolic

Amphibolic (both
catabolic & anabolic)
Serves 2 purposes:
1. Oxidize Acetyl-CoA
to CO2 to produce
energy (ATP &
reducing power of
NADH & FADH2)involved in the
aerobic catabolism
of carbohydrates,
lipids and amino
acids
2. Supply precursors
for biosynthesis
(anabolism) of
carbohydrates,
lipids, amino acids,
nucleotides and
porphyrins
Require
aerobic condition

Replenish TCA- catabolism

of amino a. and fatty a.
Anabolic pathway

Summary of ATP production

In glycolysis 2 NADH
Glyceraldehyde-3-phosphate to glycerate 1,3diphosphate

Link Rxn 2 NADH

Krebs cycle
Citrate to -ketoglutarate
-ketoglutarate to succinyl CoA
2 NADH
Succinyl CoA to succinate
Succinate to fumarate
Malate to oxaloacetate 2 NADH
Total : 10 NADH and 2 FADH2

2 NADH

2 ATP
2 FADH2

When electron going through ETC, a proton gradient is

generated and ATP is produced by chemiosmosis

1 NADH can generate

3 ATP
1 FADH2 can generate
2 ATP
10 NADH
10X3 = 30 ATP
2 FADH2
2X2 = 4 ATP
Substrate level phosphorylation
(2 GTP 2 ATP)

2 ATP

TOTAL ATP from 1 glucose (aerobic)

38 ATP

*the actual may vary in different tissues.

Differences between glycolysis

& TCA cycle
Glycolysis is a linear pathway; TCA
cycle is cyclic
Glycolysis occurs in the cytosol and
TCA is in the mitochondrial matrix
Glycolysis does / does not require
oxygen; TCA requires oxygen
(aerobic)

Lipids are Involved in Generation

and Storage of Energy
The oxidation of fatty acids (FA)in triacylglycerols
are the principal storage form of energy for most
organisms

Their carbon chains are in a highly

reduced form
The energy yield per gram of fatty
acid
Energy
(kJmol -1)
oxidized is greater than that per gram of
C6 H12 O6 + 6O2
6CO2 + 6H2 O -15.9
carbohydrate
oxidized
Glucose
CH3 (CH2 ) 14 COOH + 23O2
Palmitic acid

16CO2 +16H2 O -38.9

Catabolism of Lipids - triacylglycerol

Lipases catalyze hydrolysis of bonds between fatty acid and
the rest of triacylglycerols
Phospholipases catalyze hydrolysis of bonds between fatty
acid and the rest of phosphoacylglycerols
May have multiple sites of action

Catabolism of fatty acid - -Oxidation

-Oxidation: a series
of reactions that
cleaves carbon atoms
two at a time from the
carboxyl end of a
fatty acid
The complete cycle of
one -oxidation
requires four
enzymes/steps
Take place in
mitochondria matrix

Spiral pathway
1 round of -oxidation = yield 1 NADH, 1 FADH2 and 1 acetyl-CoA