Download Introduction to metabolism

Energy, Enzymes, and Metabolism
A.
Enzymes
1.
Definitions
 Enzyme: Biological Catalyst
 Catalyst: A substance that speeds up a
chemical reaction, but does not affect the
final equilibrium concentrations of reactants
and products.
 Substrate(s): The starting material(s) (initial
reactants) that an enzyme binds to
 Product(s): The end products that the
substrate is converted into by the reaction.
2.
Mechanism of Action:
Enzymes act by lowering the Activation Energy
of a chemical reaction
Refer to: Progress of Reaction Diagram
Enzymes lower the activation energy by creating
a stabilized intermediate state known as an
“Enzyme-Substrate Complex”
A typical enzymatic reaction follows steps that
are similar to these:
 An enzyme molecule binds to a substrate
molecule to form a noncovalently bound
enzyme-substrate complex. (The substrate
binds with great specificity at the enzyme’s
active site.)
 One or more amino acids in the active site
interact with the substrate, altering it. At this
time, some products may dissociate, and
other (different) substrate molecules may
enter the active site.
 The substrate is converted into the final
product(s), which dissociate from the
enzyme.
 The enzyme molecule is now free to bind to
another substrate molecule.
Refer to: The example of the hydrolysis of
sucrose by sucrase.
3.
Cofactors and Coenzymes
These are substances that are not part of the
amino acid structure of proteins, but which are
required for the activity of certain enzymes.
Most notable of the enzymes that need
cofactors are the enzymes that catalyze
oxidation-reduction reactions.
“Cofactor” usually refers to a substance that is
noncovalently bound to the enzyme;
“coenzyme” usually refers to a covalently
bound substance.
4.
Enzyme Inhibitors
Competitive Inhibitors: Are molecules that are
chemically similar to the substrate and can
compete with the substrate for access to the
active site (like putting the wrong key in a lock,
blocking the correct key but not destroying the
keyhole)
Noncompetitive Inhibitors: Are substances that
chemically interact with the protein that the
enzyme is made of, altering the enzymes
chemical structure and destroying the active
site’s ability to bind to its substrate. A
noncompetitive inhibitor may acts on a part of
the enzyme other than its active site (like hitting
a lock with a sledgehammer, bending the
keyhole out of shape so that the key doesn’t fit
any more)
B.
Metabolism: Basic Principles
1.
Definitions
 Metabolism: The processes of catabolism
and anabolism
 Catabolism: The processes by which a living
organism obtains its energy and raw
materials from nutrients
 Anabolism: The processes by which energy
and raw materials are used to build
macromolecules and cellular structures
(biosynthesis)
2.
Reduction and Oxidation
An atom becomes more reduced when it
undergoes a chemical reaction in which it
 Gains electrons
 By bonding to a less electronegative
atom
 And often this occurs when the atom
becomes bonded to a hydrogen
An atom becomes more oxidized when it
undergoes a chemical reaction in which it
 Loses electrons
 By bonding to a more electronegative
atom
 And often this occurs when the atom
becomes bonded to an oxygen
In metabolic pathways, we are often concerned
with the oxidation or reduction of carbon.
Reduced forms of carbon (e.g. hydrocarbons,
methane, fats, carbohydrates, alcohols) carry a
great deal of potential chemical energy stored in
their bonds.
Oxidized forms of carbon (e.g. ketones,
aldehydes, carboxylic acids, carbon dioxide)
carry very little potential chemical energy in
their bonds.
Reduction and oxidation always occur together.
In a reduction-oxidation reaction (redox
reaction), one substance gets reduced, and
another substance gets oxidized. The thing that
gets oxidized is called the electron donor, and
the thing that gets reduced is called the electron
acceptor.
3.
Enzymatic Pathways for Metabolism
Metabolic reactions take place in a step-wise
fashion in which the atoms of the raw materials
are rearranged, often one at a time, until the
formation of the final product takes place.
Each step requires its own enzyme.
The sequence of enzymatically-catalyzed steps
from a starting raw material to final end
products is called an enzymatic pathway (or
metabolic pathway)
4.
Cofactors for Redox Reactions
Enzymes that catalyze redox reactions typically
require a cofactor to “shuttle” electrons from
one part of the metabolic pathway to another
part.
There are two main redox cofactors: NAD and
FAD. These are (relatively) small organic
molecules in which part of the structure can
either be reduced (e.g., accept a pair of
electrons) or oxidized (e.g., donate a pair of
electrons)
NAD(oxidized) + H + Pair of electrons 
NADH(reduced)
(Empty of electrons)
(Carrying electrons)
FAD(oxidized) + H + Pair of electrons  FADH(reduced)
(Empty of electrons)
(Carrying electrons)
In humans, NAD is derived from niacin, and FAD
is derived from riboflavin
NAD and FAD are present only in small
(catalytic) amounts – they cannot serve as the
final electron acceptor, but must be regenerated
(reoxidized) in order for metabolism to continue
5.
ATP: A “currency of energy” for many cellular
reactions
ATP stands for adenosine triphosphate. It is a
nucleotide with three phosphate groups linked
in a small chain.
The last phosphate in the chain can be removed
by hydrolysis (the ATP becomes ADP, or
adenosine diphosphate). This reaction is
energetically favorable – it has a G' of about –
7.5 kcal/mol
ATP + H2O  ADP + Phosphate + Energy (-7.5 kcal/mol)
ATP hydrolysis is used as an energy source in
many biological reactions that require energy –
for example, active transport in the sodiumpotassium pump (see last section)
During catabolism, energy released from the
oxidation of carbon is captured and used to
synthesize ATP from ADP and phosphate.
ADP + Phosphate + Energy  ATP + H2O