Dasar-dasar metabolisme

dr. Rohmania Setiarini

Cellular Metabolism
Metabolic processes – all chemical reactions that
occur in the body

Two types of metabolic reactions

Anabolism Catabolism
• larger molecules are • larger molecules are
made broken down
• requires energy • releases energy
Anabolism
Anabolism provides the substances needed for cellular growth
and repair

Dehydration synthesis
• type of anabolic process
• used to make polysaccharides, triglycerides, and proteins
• produces water
Anabolism
Catabolism
Catabolism breaks down larger molecules into smaller ones

Hydrolysis
• a catabolic process
• used to decompose carbohydrates, lipids, and proteins
• water is used
• reverse of dehydration synthesis
Catabolism
Metabolic Reactions
Enzymes

• control rates of metabolic reactions, as catalyst

• lower activation energy needed to start reactions
• globular proteins with specific shapes
• not consumed in chemical reactions
• substrate specific
• shape of active site determines substrate
Metabolic Reactions
Metabolic pathways
• series of enzyme-controlled reactions leading to
formation of a product
• each new substrate is the product of the previous
reaction

Enzyme names commonly

• reflect the substrate
• have the suffix – ase
• sucrase, lactase, protease, lipase
 Course of
reaction EA
without without
enzyme enzyme EA with
enzyme
is lower
Free energy

Reactants

Course of G is unaffected
reaction by enzyme
with enzyme

Products

Progress of the reaction

 1 Substrates enter active site.
2 Substrates are held
in active site by weak
interactions.

Substrates
Enzyme-substrate
complex

Active
site

Enzyme
 1 Substrates enter active site.
2 Substrates are held
in active site by weak
interactions.

Substrates
Enzyme-substrate
complex 3 Active site can
lower EA and speed
up a reaction.

Active
site

Enzyme

4 Substrates are
converted to
products.
Figure 8.15-3
1 Substrates enter active site.
2 Substrates are held
in active site by weak
interactions.

Substrates
Enzyme-substrate
complex 3 Active site can
lower EA and speed
up a reaction.

6 Active
site is
available
for two new
substrate
molecules.
Enzyme

5 Products are 4 Substrates are

released. converted to
products.
Products
Factors Affecting Enzyme
Activity

Temperature
pH
Inhibitors and Activators
 Optimal temperature for Optimal temperature for
typical human enzyme (37°C) enzyme of thermophilic
(heat-tolerant)

Rate of reaction
bacteria (77°C)

0 60
20 80 40 100 120
Temperature (°C)
(a) Optimal temperature for two enzymes

Optimal pH for pepsin Optimal pH for trypsin

(stomach (intestinal
enzyme) enzyme)
Rate of reaction

0 1 5 2 3 4 6 7 8 9 10
pH
(b) Optimal pH for two enzymes
Cofactors
Cofactors are nonprotein enzyme helpers
Cofactors may be inorganic (such as a metal in
ionic form) or organic
An organic cofactor is called a coenzyme
Coenzymes include vitamins
Enzyme Inhibitors
Competitive inhibitors bind to the active
site of an enzyme, competing with the
substrate
Noncompetitive inhibitors bind to another
part of an enzyme, causing the enzyme to
change shape, changing the function
Examples of inhibitors include toxins,
poisons, pesticides, and antibiotics
(a) Normal binding (b) Competitive inhibition (c) Noncompetitive
inhibition
Substrate

Active
site
Competitive
inhibitor

Enzyme

Noncompetitive
inhibitor
Regulation Of Enzyme Activity Helps
Control Metabolism

To regulate metabolic pathways, the cell switches on or

off the genes that encode specific enzymes
Allosteric regulation is the term used to describe any
case in which a protein’s function at one site is
affected by binding of a regulatory molecule at another
site
Enzymes change shape when regulatory molecules bind
to specific sites, affecting function
Allosteric Activation and Inhibition

Most allosterically regulated enzymes are made

from polypeptide subunits
Each enzyme has active and inactive forms
The binding of an activator stabilizes the active
form of the enzyme
The binding of an inhibitor stabilizes the
inactive form of the enzyme
 Allosteric Regulation of Enzymes
Allosteric regulation may either inhibit or stimulate an
enzyme’s activity
Allosteric activater
Allosteric enyzme stabilizes active from
Active site
with four subunits (one of four)

Regulatory
site (one
of four) Activator
Active form Stabilized active form

Allosteric activater
stabilizes inactive form
Oscillation

Non- Inactive form Inhibitor Stabilized inactive

functional form
active
site

(a) Allosteric activators and inhibitors. In the cell, activators and inhibitors
dissociate when at low concentrations. The enzyme can then oscillate again.
 Cooperativity
Is a form of allosteric regulation that can
amplify enzyme activity
Binding of one substrate molecule to
active site of one subunit locks
all subunits in active conformation.

Substrate

Inactive form Stabilized active form

(b) Cooperativity: another type of allosteric activation. Note that the

inactive form shown on the left oscillates back and forth with the active
form when the active form is not stabilized by substrate.
Feedback Inhibition
In feedback inhibition, the end product of a
metabolic pathway shuts down the pathway
Feedback inhibition prevents a cell from
wasting chemical resources by synthesizing
more product than is needed
 Initial
substrate
Active site (threonine)
available Threonine
in active site

Enzyme 1
(threonine
Isoleucine
deaminase)
used up by
cell
Intermediate A
Active site of Feedback
enzyme 1 is inhibition Enzyme 2
no longer able
to catalyze the
Intermediate B
conversion
of threonine to Enzyme 3
intermediate A;
pathway is Intermediate C
switched off. Isoleucine
binds to Enzyme 4
allosteric
site. Intermediate D

Enzyme 5

End product
(isoleucine)
Specific Localization of Enzymes
Within the Cell

Some enzymes act as structural components

of membranes
In eukaryotic cells, some enzymes reside in
specific organelles; for example, enzymes
for cellular respiration are located in
mitochondria
 Mitochondria

The matrix contains

enzymes in solution that
are involved in one stage
of cellular respiration.

Enzymes for another

stage of cellular
respiration are
embedded in the
inner membrane.

1 m
Cellular Respiration
Occurs in three series of reactions
1. Glycolysis
2. Citric acid cycle
3. Electron transport chain
Produces
• carbon dioxide
• water
• ATP
• heat

Includes
• anaerobic reactions (without O2) - produce little ATP
• aerobic reactions (requires O2) - produce most ATP
ATP Molecules
• each ATP molecule has three parts:
• an adenine molecule
• a ribose molecule
• three phosphate molecules in a chain
• third phosphate attached by high-energy bond
• when the bond is broken, energy is transferred
• when the bond is broken, ATP becomes ADP
• ADP becomes ATP through phosphorylation
• phosphorylation requires energy released from cellular
respiration
 Adenine

Phosphate groups
Ribose

(a) The structure of ATP

Overview
 Glycolysis

• 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
 Glycolysis
Event 1 - Phosphorylation
• two phosphates added to
glucose
• requires ATP

Event 2 – Splitting (cleavage)

• 6-carbon glucose split into
two 3-carbon molecules
 Glycolysis
Event 3 – Production of NADH and ATP
• hydrogen atoms are released
• hydrogen atoms bind to NAD+ to
produce NADH
• NADH delivers hydrogen atoms to
electron transport chain if oxygen is
available
• ADP is phosphorylated to become ATP
• two molecules of pyruvic acid are
produced
 Anaerobic Reactions
If oxygen is not available -
• electron transport chain
cannot accept NADH
• pyruvic acid is converted to
lactic acid
• glycolysis is inhibited
• ATP production declines
Aerobic Reactions

If oxygen is available –
• pyruvic acid is used to
produce acetyl CoA
• citric acid cycle begins
• electron transport chain
functions
• carbon dioxide and
water are formed
• 36 molecules of ATP
produced per glucose
molecule
 Citric Acid Cycle
• begins when acetyl CoA
combines with oxaloacetic
acid to produce citric acid
• citric acid is changed into
oxaloacetic acid through a
series of reactions
• 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
Electron Transport Chain
• NADH and FADH2 carry electrons to the ETC
• ETC series of electron carriers located in cristae of mitochondria
• energy from electrons transferred to ATP synthase
• ATP synthase catalyzes the phosphorylation of ADP to ATP
• water is formed
Transition cycle
Summary of Cellular
Respiration