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ENZYME: an essential catalyst
There are two fundamental conditions for life.
First, the living entity must be able to self-replicate;
Second, the organism must be able to catalyze chemical
Reactions efficiently and selectively.
Living systems make use of energy from the environment.
Many of us, for example, consume substantial amounts of
sucrose—common table sugar—as a kind of fuel, whether in
the form of sweetened foods and drinks or as sugar itself.
The conversion of sucrose to CO2 and H2O in the presence
of oxygen is a highly exergonic process, releasing free energy
that we can use to think, move, taste, and see.
However, a bag of sugar can remain
on the shelf for years without any obvious conversion
to CO2 and H2O. Although this chemical process
is thermodynamically favorable, it is very slow! Yet when
sucrose is consumed by a human (or almost any other
organism), it releases its chemical energy in seconds.
The difference is catalysis. Without catalysis, chemical
reactions such as sucrose oxidation could not occur on
a useful time scale, and thus could not sustain life.
HISTORY
As early as the late 17th and early 18th centuries, the digestion of meat by stomach
secretions and the conversion of starch to sugars by plant extracts and saliva were
known. However, the mechanism by which this occurred had not been identified.
1833, French chemist Anselme Payen
discovered the first enzyme,
diastase.
1850 A few decades later, when studying
the fermentation of sugar to alcohol by
yeast, Louis Pasteur came to the
conclusion that this fermentation was
catalyzed by a vital force contained
within the yeast cells called "ferments",
which were thought to function only
within living organisms.
He wrote that "alcoholic fermentation is
an act correlated with the life and
organization of the yeast cells, not with
the death or putrefaction of the cells.
1877, German physiologist Wilhelm Kühne (1837–1900) first used the term enzyme, which
comes from Greek ενζυμον, "in leaven". The word enzyme was used later to refer to nonliving
substances such as pepsin, and the word ferment was used to refer to chemical activity
produced by living organisms. In 1876, he discovered the protein-digesting enzyme trypsin.
1897, Eduard Buchner submitted his first paper on the ability of yeast extracts that
lacked any living yeast cells to ferment sugar. In a series of experiments at the
University of Berlin, he found that the sugar was fermented even when there were no
living yeast cells in the mixture. He named the enzyme that brought about the
fermentation of sucrose "zymase". In 1907, he received the Nobel Prize in Chemistry
"for his biochemical research and his discovery of cell-free fermentation". Following
Buchner's example, enzymes are usually named according to the reaction they carry
out. Typically, to generate the name of an enzyme, the suffix -ase is added to the
name of its substrate (e.g., lactase is the enzyme that cleaves lactose) or the type of
reaction (e.g., DNA polymerase forms DNA polymers).
1926, James B. Sumner showed that the enzyme urease
was a pure protein and crystallized it; Sumner did
likewise for the enzyme catalase in 1937. The conclusion
that pure proteins can be enzymes was definitively
proved by John Howard Northrop and Wendell Meredith
Stanley, who worked on the digestive enzymes pepsin
(1930), trypsin and chymotrypsin. These three scientists
were awarded the 1946 Nobel Prize in Chemistry.
During this period
J. B. S. Haldane wrote a treatise entitled Enzymes. Although the molecular nature
of enzymes was not yet fully appreciated, Haldane made the remarkable suggestion
that weak bonding interactions between an enzyme and its substrate might be used
to catalyze a reaction. This insight lies at the heart of our current understanding
of enzymatic catalysis.
1964 This discovery that enzymes could be crystallized eventually allowed their
structures to be solved by x-ray crystallography. This was first done for lysozyme, an
enzyme found in tears, saliva and egg whites that digests the coating of some
bacteria; the structure was solved by a group led by David Chilton Phillips and
published in 1965. This high-resolution structure of lysozyme marked the beginning of
the field of structural biology and the effort to understand how enzymes work at an
atomic level.
General Characteristics of Enzymes
Enzymes are central to every biochemical process. Acting in organized sequences,
they catalyze the hundreds of stepwise reactions that degrade nutrient molecules,
conserve and transform chemical energy, and make biological macromolecules from
simple precursors.
1. Organic Nature: Enzymes are in general globular proteins and range from just
62 amino acid residues in size, for the monomer of 4-oxalocrotonate
tautomerase, to over 2,500 residues in the animal fatty acid synthase. A small
number of RNA-based biological catalysts exist, with the most common being
the ribosome; these are referred to as either RNA-enzymes or ribozymes. The
activities of enzymes are determined by their three-dimensional structure.
However, although structure does determine function, predicting a novel
enzyme's activity just from its structure is a very difficult problem that has not
yet been solved.
2. Catalytic Efficiency: Catalyst - a substance that speeds up the rate of a
reaction without being changed itself by lowering the activation energy of a
reaction. The same reaction would eventually occur, but not at a rate fast
enough for survival. For example, the hydrolysis of protein in our diet would
occur without a catalyst, but not fast enough to meet the body’s requirements
for amino acids.
3. Specificity: Enzymes are usually very specific as to which reactions they
catalyze and the substrates that are involved in these reactions.
Complementary shape, charge and hydrophilic/hydrophobic characteristics
of enzymes and substrates are responsible for this specificity. Enzymes can
also show impressive levels of stereospecificity, regioselectivity and
chemoselectivity.
Some of the enzymes showing the highest specificity and accuracy are
involved in the copying and expression of the genome. These enzymes have
"proof-reading" mechanisms. Here, an enzyme such as DNA polymerase
catalyzes a reaction in a first step and then checks that the product is
correct in a second step. This two-step process results in average error
rates of less than 1 error in 100 million reactions in high-fidelity mammalian
polymerases. Similar proofreading mechanisms are also found in RNA
polymerase and aminoacyl tRNA synthetases.
4. Enzyme regulation: Various ways
5. Enzyme production : induction/inhibition
Transcription and translation of enzyme genes can be enhanced or diminished by a
cell in response to changes in the cell's environment. This form of gene regulation is
called enzyme induction and inhibition.
For example, bacteria may become resistant to antibiotics such as penicillin because
enzymes called beta-lactamases are induced that hydrolyze the crucial beta-lactam
ring within the penicillin molecule.
Another example are enzymes in the liver called cytochrome P450 oxidases, which
are important in drug metabolism.
6. Enzymes can be compartmentalized, with different metabolic pathways occurring in
different cellular compartments. For example, fatty acids are synthesized by one set of
enzymes in the cytosol, endoplasmic reticulum and the Golgi apparatus and used by a different
set of enzymes as a source of energy in the mitochondrion, through β-oxidation.
7. Disease & Enzyme:
Since the tight control of enzyme activity is essential for homeostasis, any
malfunction (mutation, overproduction, underproduction or deletion) of a single
critical enzyme can lead to a genetic disease. The importance of enzymes is
shown by the fact that a lethal illness can be caused by the malfunction of just
one type of enzyme out of the thousands of types present in our bodies.
The International Union of Biochemistry and Molecular Biology
(IUBMB)
Founded in 1955 - unites biochemists and molecular biologists in 77 countries that
belong to the Union as an Adhering Body or Associate Adhering Body which is
represented as a biochemical society, a national research council or an academy of
sciences. The Union is devoted to promoting research and education in biochemistry
and molecular biology throughout the world and gives particular attention to areas
where the subject is still in its early development.
The IUBMB is one of 26 Scientific Unions affiliated with the International Council of
Science (ICSU), an umbrella organization for scientists worldwide. ICSU was
created in 1931 to encourage international scientific activity, to affirm the rights
of scientists without regard to race, religion, political philosophy, ethnic origin, sex
or language, to join in international scientific affairs for the benefit of mankind.
The IUBMB has been a member of ICSU since 1955 (until 1991 as IUB).
IUBMB Activities
The IUBMB is engaged in variety of activities. For details follow the links to the left, and above (for Publications):
• Every three years, the world's biochemists come together at the IUBMB International Congress of Biochemistry
and Molecular Biology.
• Travel awards and a special two-day pre-Congress programme for young scientists, called Young Scientists
Program (YSP) is a special feature attached to this event.
• IUBMB Conferences take place in the years between IUBMB Congresses. They enhance the visibility of IUBMB in
regions of significant or major biochemical activity and present opportunities for review of advances in a limited
number of topic areas.
• A new activity is the IUBMB Special Meeting, a more focused meeting than the conference type.
• IUBMB sponsors international Symposia and Workshops worldwide on focused topics.
• The Wood-Whelan Fellowships provide short-term fellowships for younger biochemists to travel to other
laboratories to undertake research that cannot be done in their own laboratories.
• Reaching individual biochemists is also the purpose of another very important function of the IUBMB, that of
publishing journals containing news, reviews, information, original research and also maps and nomenclature.
• The IUBMB Jubilee Lectures have been established to commemorate the 50th anniversary of the first
International Congress of Biochemistry held in Cambridge, UK in 1949, at which steps were taken that led to
formation of IUB (IUBMB since 1991)
The International Union of Pure and
Applied Chemistry (IUPAC) and the
International Union of Biochemistry
and Molecular Biology (IUBMB) have
established the IUPAC-IUBMB Joint
Commission on Biochemical
Nomenclature (JCBN) and the
Nomenclature Committee of the
International Union of Biochemistry
and Molecular Biology (NC-IUBMB).
The purpose of the committees is to facilitate communication of biochemical information by encouraging
scientists to use generally understood terminology. The committees seek advice from experts in the
diverse fields of biochemistry about matters where communication is difficult because of inconsistent
practices.
Procedures for establishing new recommendations
The initial recommendations for any topic are always prepared by experts in the subject area, but are subsequently
studied by the nomenclature committees in an effort to harmonize them with recommendations in related areas of
biochemistry, or indeed in chemistry and other disciplines.
Although this step often appears unnecessary to experts in a restricted area of the subject, its importance emerges
when one attempts to present information on a broader scale or to a broader audience.
Recommendations of the nomenclature committees are published in the primary research literature. All JCBN
recommendations are published in Pure and Applied Chemistry, and all JCBN and NC-IUBMB recommendations are
currently published in the European Journal of Biochemistry, by courtesy of FEBS.
Many documents appear also in other journals, and any journal wishing to republish a document can normally obtain
reproduction-quality proofs from the European Journal of Biochemistry, to avoid the need for re-setting.
The different kinds of enzymes are named in different ways
• Most often enzymes are named by adding a suffix 'ase' to the root word of the substrate. For
example, Lipase (fat hydrolysing enzyme), Sucrase (breaking down sucrose).
• Sometimes the enzymes are named on the basis of the reaction that they catalyse. For example,
Polymerase (aids in polymerisation), Dehydrogenase (removal of H atoms).
• Some enzymes have been named based on the source from which they were first identified. For
example, Papayin from papaya.
• The names of some enzymes ends with an 'in' indicating that they are basically proteins. For
example, Pepsin, Trypsin etc.
Enzyme Nomenclature
• An enzyme's name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending
in -ase. Examples are lactase, alcohol dehydrogenase and DNA polymerase.
• This may result in different enzymes, called isozymes, with the same function having the same basic name.
Isoenzymes have a different amino acid sequence and might be distinguished by their optimal pH, kinetic
properties or immunologically.
• Isoenzyme and isozyme are homologous proteins.
• Furthermore, the normal physiological reaction an enzyme catalyzes may not be the same as under artificial
conditions. This can result in the same enzyme being identified with two different names. For example, glucose
isomerase, which is used industrially to convert glucose into the sweetener fructose, is a xylose isomerase in vivo
(within the body).
• The International Union of Biochemistry and Molecular Biology have developed a nomenclature for enzymes, the
EC numbers; each enzyme is described by a sequence of four numbers preceded by "EC". The first number
broadly classifies the enzyme based on its mechanism.
EC 1 Oxidoreductases: catalyze oxidation/reduction reactions
EC 2 Transferases: transfer a functional group (e.g. a methyl or phosphate group)
EC 3 Hydrolases: catalyze the hydrolysis of various bonds
EC 4 Lyases: cleave various bonds by means other than hydrolysis and oxidation
EC 5 Isomerases: catalyze isomerization changes within a single molecule
EC 6 Ligases: join two molecules with covalent bonds
• According to the naming conventions, enzymes are generally classified into six main family classes and many
sub-family classes.
• Some web-servers, e.g., EzyPred and
bioinformatics tools have been developed to
predict which main family class and subfamily class an enzyme molecule belongs to
according to its sequence information alone.
Format of number
Scheme for the classification of enzymes and the generation of EC numbers
The first Enzyme Commission, in its report in 1961, devised a system for classification
of enzymes that also serves as a basis for assigning code numbers to them.
These code numbers, prefixed by EC, which are now widely in use, contain four
elements separated by points, with the following meaning:
(i) the first number shows to which of the six main divisions (classes) the enzyme
belongs,
(ii) the second figure indicates the subclass,
(iii) the third figure gives the sub-subclass,
(iv) the fourth figure is the serial number of the enzyme in its sub-subclass.
For example,
Tripeptide aminopeptidases have the code "EC 3.4.11.4", whose components indicate the following groups of
enzymes:
EC 3 enzymes are hydrolases (enzymes that use water to break up some other molecule ) catalyzed reaction
EC 3.4 are hydrolases that act on peptide bonds- specific chemical interaction
EC 3.4.11 are those hydrolases that cleave off the amino-terminal amino acid from a polypeptide-regiospecificity
EC 3.4.11.4 are those that cleave off the amino-terminal end from a tripeptide