Mendiola, Honey Joy A.

BS Pharmacy 2

OUTLINE ULO 8

1. Enzymes – highly specialized protein molecules that act as biochemical catalysts.

Enzymes have common names that provide information about their function rather than
their structure. The suffix -ase is characteristic of most enzyme names.
2. Enzyme structure – Simple enzymes are composed only of protein (amino acids).
Conjugated enzymes have a nonprotein portion (cofactor) in addition to a protein portion
(apoenzyme). Cofactors may be small organic molecules (coenzymes) or inorganic
ions.
3. Enzyme classification – There are six classes of enzymes based on function:
oxidoreductases, transferases, hydrolases, lyases, isomerases, and ligases.
4. Enzyme active site – An enzyme active site is the relatively small part of the
enzyme that is actually involved in catalysis. It is where substrate binds to the enzyme.
5. Lock-and-key model of enzyme activity – The active site in an enzyme has a fixed,
rigid geometrical conformation. Only substrates with a complementary geometry can be
accommodated at the active site.
6. Induced-fit model of enzyme activity – The active site in an enzyme can undergo
small changes in geometry in order to accommodate a series or related substrates.
7. Enzyme activity – Enzyme activity is a measure of the rate at which an enzyme
converts substrate to products. Four factors that affect enzyme activity are temperature,
pH, substrate concentration, and enzyme concentration.
8. Enzyme inhibition – An enzyme inhibitor slows or stops the normal catalytic function
of an enzyme by binding to it. Three modes of inhibition are reversible competitive
inhibition, reversible noncompetitive inhibition, and irreversible inhibition.
9. Allosteric enzyme – An allosteric enzyme is an enzyme with two or more protein
chains and two kinds of binding sites (for substrate and regulator).
10. Zymogen – an inactive precursor of a proteolytic enzyme; the zymogen is activated
by a chemical reaction that removes part of its structure.
11. Covalent modification – is a cellular process for regulation of enzyme activity in
which the structure of an enzyme is modified through formation of, or breaking of, a
covalent bond. The most commonly encountered type of covalent modification involves
a phosphate group being added to, or removed from, an enzyme.
12. Vitamins – an organic compound necessary in small amounts for the normal
growth of humans and some animals. Vitamins must be obtained from dietary sources
because they cannot be synthesized in the body.
Mendiola, Honey Joy A.
BS Pharmacy 2

13. Water-soluble vitamins – Vitamin C and the eight B vitamins are the water-soluble
vitamins. Vitamin Cis essential for the proper formation of bones and teeth and is also
an important antioxidant. All eight B vitamins function as coenzymes.
14. Fat-soluble vitamins – The four fat-soluble vitamins are vitamins A, D, E, and K.
The best-known function of vitamin A is its role in vision. Vitamin D is essential for the
proper use of calcium and phosphorus to form bones and teeth. The primary function of
vitamin E is as an antioxidant. Vitamin K is essential in the regulation of blood clotting.

Enzymes
General Characteristics of Enzymes
 Enzymes are usually proteins that act as biological catalysts.
 Each cell in the human body contains thousands of different enzymes.
 Enzymes cause cellular reactions to occur millions of times faster than
corresponding uncatalyzed reactions.
 An enzyme speeds a reaction by lowering the activation energy, changing the
reaction pathway that
 provides a lower energy route for conversion of substrate to product.
 As catalysts enzymes are NOT consumed in the reactions

Enzyme Structure
Simple and Conjugated Enzymes
 Most enzymes are globular proteins; some are simple proteins, others are
conjugated proteins.
 Simple enzyme: composed only of protein (amino acid chains).
o It is the 3 degree structure of the simple enzymes that makes it biologically
active.
 Conjugated enzyme: has a non-protein part in addition to a protein part.
1. Apoenzyme → protein part; inactive in itself.
2. Cofactor/Coenzyme → nonprotein organic (coenzyme /co-substrate) or inorganic
(cofactor) moiety; the activator; loosely bound to protein.
o Apoenzyme + Cofactor = Holoenzyme (biologically active conjugated
enzyme)
Mendiola, Honey Joy A.
BS Pharmacy 2

Nomenclature and Classification of Enzymes

 Most commonly named with reference to their function.
o type of reaction catalyzed
o identity of the substrate
 A substrate is the reactant in an enzyme-catalyzed reaction:
 The substrate is the substance upon which the enzyme acts.”
o e. g., In the fermentation process, sugar is converted to alcohol, therefore
in this reaction sugar is the substrate.

Three Important Aspects of the Naming Process

1. Suffix -ase identifies it as an enzyme.
 e.g., urease, sucrase, and lipase are all enzyme designations
 exception: the suffix -in is still found in the names of some digestive enzymes,
e.g., trypsin, chymotrypsin, and pepsin
2. Type of reaction catalyzed by an enzyme is often used as a prefix.
 e.g., oxidase - catalyzes an oxidation reaction,
 e.g., hydrolase - catalyzes a hydrolysis reaction
3. Identity of substrate is often used in addition to the type of reaction.
 e.g. glucose oxidase, pyruvate carboxylase, and succinate dehydrogenase

Oxidoreductase
 An oxidoreductase enzyme catalyzes an oxidation–reduction reaction:
o Oxidation and reduction reactions are always linked to one another.
o An oxidoreductase requires a coenzyme that is either oxidized or reduced
as the substrate in the reaction.
o e.g., lactate dehydrogenase is an oxidoreductase and NAD+ is the
coenzyme in this reaction.

Transferase
 A transferase is an enzyme that catalyzes the transfer of a functional group from
one molecule to another.
Two major subtypes:
1. Kinases - catalyze transfer of a phosphate group from adenosine triphosphate
(ATP) to a substrate.
Mendiola, Honey Joy A.
BS Pharmacy 2

2. Transaminases - catalyze transfer of an amino group to a substrate

Hydrolase
 A hydrolase is an enzyme that catalyzes a hydrolysis reaction.
 The reaction involves addition of a water molecule to a bond to cause bond
breakage.
 Hydrolysis reactions are central to the process of digestion:
o carbohydrases hydrolyze glycosidic bonds in oligo- and polysaccharides
o proteases effect the breaking of peptide linkages in proteins
o lipases effect the breaking of ester linkages in triacylglycerols

Lyase
 A lyase is an enzyme that catalyzes the addition or the removal of a group in a
manner that does not involve hydrolysis or oxidation.
o dehydratase: effects the removal of the components of water to form a
double bond
o hydratase: effects the addition of the components of water to a double
bond

Isomerase
 An isomerase is an enzyme that catalyzes the isomerization (rearrangement of
atoms) of a substrate in a reaction, converting it into a molecule isomeric with
itself.
o racemases – conversion of D- to L- isomer or vice versa
o mutases – transfer of a functional group within a molecule

Ligase
 A ligase is an enzyme that catalyzes the formation of a bond between two
molecules involving ATP hydrolysis to ADP:
o ATP hydrolysis is required because such reactions are energetically
unfavorable
o synthetases – formation of new bond between two substrates with
participation of ATP
o carboxylases – formation of new bond between substrate and carbon
dioxide with participation of ATP
Mendiola, Honey Joy A.
BS Pharmacy 2

Models of Enzyme Action

Enzyme Active Site
 Explanations of how enzymes function as catalysts in biochemical systems are
based on the concepts of an enzyme active site and enzyme-substrate complex
formation.
 The active site: relatively small part of an enzyme’s structure that is actually
involved in catalysis:
o Where substrate binds to enzyme.
o Formed due to folding and bending of the protein.
o Usually a “crevice like” location in the enzyme.
o Some enzymes have more than one active site.

Enzyme Substrate Complex

 Intermediate reaction species formed when substrate binds with the active site
 Needed for the activity of enzyme
 Orientation and proximity is favorable and reaction is fast

Two Models for Substrate Binding to Enzyme

 Lock-and-Key model:
o In this model, the active site in the enzyme has a fixed, rigid geometrical
conformation.
o Only substrate of specific shape can bind with active site; a substrate
whose shape and chemical nature are complementary to those of the
active site can interact with the enzyme.

Enzyme Specificity
 Absolute Specificity:
 Stereochemical Specificity:
 Group Specificity:
 Linkage Specificity:

Factors That Affect Enzyme Activity

Enzyme Activity
Mendiola, Honey Joy A.
BS Pharmacy 2

 A measure of the rate at which enzyme converts substrate to products in a

biochemical reaction

Four factors affect enzyme activity:

o Temperature
o pH
o Substrate concentration
o Enzyme concentration

Temperature
 Higher temperature results in higher kinetic energy which causes an increase in
number of reactant collisions, therefore there is higher activity.
 Optimum temperature: temperature at which the rate of enzyme- catalyzed
reaction is maximum.
 Optimum temperature for human enzymes is 37ºC (body temperature).
 Increased temperature (high fever) leads to decreased enzyme activity.

pH
 Drastic changes in pH can result in denaturation of proteins.
 Optimum pH: pH at which enzyme has maximum activity.
 Most enzymes have optimal activity in the pH range of 7.0 - 7.5
 Exception: digestive enzymes
o pepsin: optimum pH = 2.0
o trypsin: optimum pH = 8.0

Prescription Drugs That Inhibit Enzyme Activity

Clinical Applications of Enzymes
 Different cells in the body produce enzymes for the same type of reactions.
 Enzymes that catalyze the same reactions but vary slightly in structure are called
isoenzymes.
o For example, there are five isoenzymes for lactate dehydrogenase (LDH),
an enzyme that converts lactic acid to pyruvic acid.

Enzyme Structure
Coenzymes / Cofactors
Mendiola, Honey Joy A.
BS Pharmacy 2

 The water-soluble vitamins, which include all B-vitamins and Vitamin C, act as
coenzymes or coenzyme precursors.
 Cofactors are bound to the enzyme for it to maintain the correct configuration at
the active site.
 Provide additional chemically reactive functional group.

General Characteristics of Vitamins

Vitamin
 An organic compound essential for proper functioning of the body.
 Must be obtained from dietary sources because human body can’t synthesize
them in enough amounts.
 Needed in micro and milligram quantities.
o 1 gram of vitamin B is sufficient for 500,000 people
 Enough vitamin can be obtained from balanced diet.
 Supplemental vitamins may be needed after illness.
 Many enzymes contain vitamins as part of their structures - conjugated enzymes.
 Two classes of vitamins
 Water-Soluble and Fat-Soluble
 Synthetic and natural vitamins have the same function
o 13 Known vitamins

Water-Soluble Vitamins: Vitamin C

 Humans, monkeys, apes and guinea pigs need dietary vitamins.
 Co-substrate in the formation of structural protein collagen.
o Hydroxylation of lysine and proline in collagen formation are catalyzed by
enzymes that require ascorbic acid (Vit. C) and iron.
o In Vit. C deficiency, hydroxylation is impaired, and the triple helix of the
collagen is not assembled properly.
o Persons deprived of Vit. C develops scurvy, a disease whose symptoms
include skin lesions, fragile blood vessels, loose teeth, and bleeding gums

Water-Soluble Vitamins: The B Vitamins

 Major function: B Vitamins are components of many coenzymes.
 Serve as temporary carriers of atoms or functional groups in redox and group
transfer reactions associated with metabolism.
 The preferred and alternative names for the B vitamins.
o Thiamin (vitamin B1)
Mendiola, Honey Joy A.
BS Pharmacy 2

o Riboflavin (vitamin B2)

o Niacin (nicotinic acid, nicotinamide, vitamin B3)
o Pantothenic acid (vitamin B5)
o Vitamin B6 (pyridoxine, pyridoxal, pyridoxamine)
o Folate (folic acid)
o Vitamin B12 (cobalamin)
o Biotin

Functions of Vitamin A
 Vision: in the eye- vitamin A combines with opsin protein to form the visual
pigment rhodopsin which further converts light energy into nerve impulses that
are sent to the brain.
 Regulating Cell Differentiation: a process in which immature cells change to
specialized cells with function.
o example: differentiation of bone marrow cells white blood cells and red
blood cells.
 Maintenance of the health of epithelial tissues via epithelial tissue differentiation.
o lack of vitamin A causes skin surface to become drier and harder than
normal.
 Reproduction and Growth: in men, vitamin A participates in sperm development.
In women, normal fetal development during pregnancy requires vitamin A.

Vitamin E - Antisterility Vitamin

 Alpha-tocopherol is the most active biological active form of Vitamin E
 Tocopherol → Greek, promoter of childbirth
 Functions in the body as an antioxidant in that it inhibits the oxidation of
unsaturated fatty acids by O2.
 Primary function: Antioxidant – protects against oxidation of other compounds.

Vitamin K - Antihemorrhagic Vitamin

 Vit K is synthesized by bacteria that grow in colon.
 Active in the formation of proteins involved in regulating blood clotting.
 Deficiency may occur during the first few days after birth, because newborns lack
the intestinal bacteria that produce Vit. K and because they have no store of Vit.
K (it does not cross the placenta).
 Deficiency may also occur following antibiotic therapy that sterilizes the gut.