University of Karbala

College of Applied Medical Sciences

Department of pathological Analysis
Stage: Second
Study : Evening

Enzymes

‫المشرف‬
‫م خمائل حسن عبيد‬.‫م‬

‫اعداد الطالب‬
‫مهدي ناظم علي‬
Introduction
Enzymes (/ˈɛnzaɪmz/) are proteins that act as biological catalysts by
accelerating chemical reactions. The molecules upon which enzymes may act
are called substrates, and the enzyme converts the substrates into different
molecules known as products. Almost all metabolic processes in the cell need
enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic
pathways depend upon enzymes to catalyze individual steps. The study of
enzymes is called enzymology and the field of pseudoenzyme analysis
recognizes that during evolution, some enzymes have lost the ability to carry
out biological catalysis, which is often reflected in their amino acid sequences
and unusual 'pseudocatalytic' properties.Enzymes are known to catalyze more
than 5,000 biochemical reaction types.

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 (The enzyme glucosidase converts the sugar maltose into two glucose sugars.
Active site residues in red, maltose substrate in black, and NAD cofactor in
yellow)
Etymology and history
By 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 but the mechanisms by which these occurred had not been
identified. French chemist Anselme Payen was the first to discover an enzyme,
diastase, in 1833. A few decades later, when studying the fermentation of sugar
to alcohol by yeast, Louis Pasteur concluded that this fermentation was caused
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."

Classification and nomenclature

Enzymes can be classified by two main criteria: either amino acid sequence
similarity (and thus evolutionary relationship) or enzymatic activity.
Enzyme activity 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. Different enzymes that
catalyze the same chemical reaction are called isozymes. The International
Union of Biochemistry and Molecular Biology have developed a nomenclature
for enzymes, the EC numbers (for "Enzyme Commission"). Each enzyme is
described by "EC" followed by a sequence of four numbers which represent the
hierarchy of enzymatic activity (from very general to very specific). That is, the
first number broadly classifies the enzyme based on its mechanism while the
other digits add mor]e and more specificity.
Sequence similarity EC categories do not reflect sequence similarity. For

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instance, two ligases of the same EC number that catalyze exactly the same
reaction can have completely different sequences. Independent of their function,
enzymes, like any other proteins, have been classified by their sequence
similarity into numerous families. These families have been documented in
dozens of different protein and protein family databases such as Pfam.
Non-homologous isofunctional enzymes. Unrelated enzymes that have the
same enzymatic activity have been called non-homologous isofunctional
enzymes. Horizontal gene transfer may spread these genes to unrelated species,
especially bacteria where they can replace endogenous genes of the same
function, leading to hon-homologous gene displacement.
Structure
Enzymes are generally globular proteins, acting alone or in larger complexes.
The sequence of the amino acids specifies the structure which in turn
determines the catalytic activity of the enzyme. Although structure determines
function, a novel enzymatic activity cannot yet be predicted from structure
alone. Enzyme structures unfold (denature) when heated or exposed to chemical
denaturants and this disruption to the structure typically causes a loss of
activity. Enzyme denaturation is normally linked to temperatures above a
species' normal level; as a result, enzymes from bacteria living in volcanic
environments such as hot springs are prized by industrial users for their ability
to function at high temperatures, allowing enzyme-catalysed reactions to be
operated at a very high rate.
Enzymes are usually much larger than their substrates. Sizes range from just 62
amino acid residues, for the monomer of 4-oxalocrotonate tautomerase, to over
2,500 residues in the animal fatty acid synthase. Only a small portion of their
structure (around 2–4 amino acids) is directly involved in catalysis: the catalytic
site. This catalytic site is located next to one or more binding sites where
residues orient the substrates. The catalytic site and binding site together
compose the enzyme's active site. The remaining majority of the enzyme
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structure serves to maintain the precise orientation and dynamics of the active
site.

(Enzyme activity initially increases with temperature (Q10 coefficient) until the
enzyme's structure unfolds (denaturation), leading to an optimal rate of reaction
at an intermediate temperature)
Cofactors
Some enzymes do not need additional components to show full activity. Others
require non-protein molecules called cofactors to be bound for activity.
Cofactors can be either inorganic (e.g., metal ions and iron–sulfur clusters) or
organic compounds (e.g., flavin and heme). These cofactors serve many
purposes; for instance, metal ions can help in stabilizing nucleophilic species
within the active site. Organic cofactors can be either coenzymes, which are
released from the enzyme's active site during the reaction, or prosthetic groups,
which are tightly bound to an enzyme. Organic prosthetic groups can be
covalently bound (e.g., biotin in enzymes such as pyruvate carboxylase). An
example of an enzyme that contains a cofactor is carbonic anhydrase, which
uses a zinc cofactor bound as part of its active site. These tightly bound ions or
molecules are usually found in the active site and are involved in catalysis. For
example, flavin and heme cofactors are often involved in redox reactions.
Enzymes that require a cofactor but do not have one bound are called
apoenzymes or apoproteins. An enzyme together with the cofactor(s) required
for activity is called a holoenzyme (or haloenzyme). The term holoenzyme can
also be applied to enzymes that contain multiple protein subunits, such as the
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DNA polymerases; here the holoenzyme is the complete complex containing all
the subunits needed for activity.

Biological function
Enzymes serve a wide variety of functions inside living organisms. They are
indispensable for signal transduction and cell regulation, often via kinases and
phosphatases. They also generate movement, with myosin hydrolyzing
adenosine triphosphate (ATP) to generate muscle contraction, and also transport
cargo around the cell as part of the cytoskeleton. Other ATPases in the cell
membrane are ion pumps involved in active transport. Enzymes are also
involved in more exotic functions, such as luciferase generating light in
fireflies. Viruses can also contain enzymes for infecting cells, such as the HIV
integrase and reverse transcriptase, or for viral release from cells, like the
influenza virus neuraminidase. An important function of enzymes is in the
digestive systems of animals. Enzymes such as amylases and proteases break
down large molecules (starch or proteins, respectively) into smaller ones, so
they can be absorbed by the intestines.
Starch molecules, for example, are too large to be absorbed from the intestine,
but enzymes hydrolyze the starch chains into smaller molecules such as maltose
and eventually glucose, which can then be absorbed. Different enzymes digest
different food substances. In ruminants, which have herbivorous diets,
microorganisms in the gut produce another enzyme, cellulase, to break down
the cellulose cell walls of plant fiber.
Metabolism
Several enzymes can work together in a specific order, creating metabolic
pathways. In a metabolic pathway, one enzyme takes the product of another
enzyme as a substrate. After the catalytic reaction, the product is then passed on
to another enzyme. Sometimes more than one enzyme can catalyze the same
reaction in parallel; this can allow more complex regulation: with, for example,

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a low constant activity provided by one enzyme but an inducible high activity
from a second enzyme.
Enzymes determine what steps occur in these pathways. Without enzymes,
metabolism would neither progress through the same steps and could not be
regulated to serve the needs of the cell. Most central metabolic pathways are
regulated at a few key steps, typically through enzymes whose activity involves
the hydrolysis of ATP. Because this reaction releases so much energy, other
reactions that are thermodynamically unfavorable can be coupled to ATP
hydrolysis, driving the overall series of linked metabolic reactions.

References
1. Stryer L, Berg JM, Tymoczko JL (2002). Biochemistry.

2. Murphy JM, Farhan H, Eyers PA (April 2017). "Bio-Zombie: the rise of

pseudoenzymes in biology". Biochemical Society Transactions. 45 (2):
537–544.

3. Murphy JM, Zhang Q, Young SN, Reese ML, Bailey FP, Eyers PA, et al.
(January 2014). "A robust methodology to subclassify pseudokinases
based on their nucleotide-binding properties". The Biochemical Journal.
457.

4. Schomburg I, Chang A, Placzek S, Söhngen C, Rother M, Lang M, et al.

(January 2013). "BRENDA in 2013: integrated reactions, kinetic data,
enzyme function data, improved disease classification: new options and
contents in BRENDA". Nucleic Acids Research. 41

5. Radzicka A, Wolfenden R (January 1995). "A proficient enzyme".

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 Science. 267 (5194): 90–93.

6. Callahan BP, Miller BG (December 2007). "OMP decarboxylase--An

enigma persists". Bioorganic Chemistry. 35 (6): 465–469.

7. Willstätter R (1927). "Faraday lecture. Problems and methods in enzyme

research". Journal of the Chemical Society (Resumed): 1359–1381.

8. Johnson LN, Petsko GA (July 1999). "David Phillips and the origin of
structural enzymology". Trends in Biochemical Sciences. 24 (7): 287–
289.

9. Anfinsen CB (July 1973). "Principles that govern the folding of protein

chains". Science. 223–230.