microsoft powerpoint - enzyme, biokimia medicine
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BIOKIMIA MEDICINE
BIOKIMIA MEDICINE
SUBEHAN,
SUBEHAN, M.Pharm
.Sc
M.Pharm
.Sc., PhD
., PhD
ENZYMES
ENZYMES
MEC
HANIS
M O
F ACT
ION, IN
HIB
ITIO
N &
DIS
FUNCT
ION
MEC
HANIS
M O
F ACT
ION, IN
HIB
ITIO
N &
DIS
FUNCT
ION
INTRODUCTION
INTRODUCTION
�Enzymes are biological catalysis
-substance of biological origin that accelerate
chemical reactions.
-the vast majority of enzyme are proteins.
-catalytically active ribonucleic acids “ribozymes”.
-in general, name suffix “-ase”
�The presence and m
aintenance of a complete and
balanced set of enzymes is essential for
-the breakdown of nutrients to supply energy, and
chemical building block;
-the assembly of those building blocks into proteins,
DNA, membranes, cells, and tissues;
-and the harnessing of energy to power cell motility and
muscle contraction.
��Deficiency in quantity and catalytic activity
Deficiency in quantity and catalytic activity
can result from:
can result from:
-genetic defects,
-nutritional deficits,
-or, toxins.
��Defective enzymes can result from:
Defective enzymes can result from:
-genetic m
utation
-infections by viral or bacterial pathogens.
��Medical scientists:
Medical scientists:
-imbalances in enzyme activity
pharm
acologic agent to inhibit.
-investigating gene therapy
remedy deficits in enzyme level and function.
Enzyme activity
Enzyme activity
International unit, U: µmolturnover min
-1
1 U = 16.7 nkat
-Catalyze the conversion of one/more
compounds (substrate) into one/more
different compounds
Turnover (m
ol product s-1) with enzyme
Enzyme activity (mol s-1= kat)
Turnover (m
ol product s-1)
without enzyme
-Enhance the rate of the corresponding
noncatalyzedreaction by > 106
-Neither consumed nor perm
anently
altered in the reaction.
-Selective catalyst.
substrate piruvat------------
L-lactate.
Enzyme Nomenclature
Enzyme Nomenclature
International Union of Biochemist (IUB)
International Union of Biochemist (IUB)
��In general:
In general:
--Type of reaction catalyzed followed by suffix
Type of reaction catalyzed followed by suffix ––ase
ase..
-dehydrogenase, protease, etc.
��IUB:
IUB:
--Each enzyme has a unique name and code number that reflect the
Each enzyme has a unique name and code number that reflect the type of
type of
reaction catalyzed and the substrate involved.
reaction catalyzed and the substrate involved.
--EC 1.2.3.4
EC 1.2.3.4
--EC, Enzyme catalog
EC, Enzyme catalog
--1, Class
1, Class
--2, subclasses
2, subclasses
--3,
3, subsubclasses
subsubclasses
--4, where the enzyme belongs in the
4, where the enzyme belongs in the subsubclases
subsubclases..
--EC 2.7.1.1
--class 2,
class 2, transferase
transferase
--subclass 7, transfer of a
subclass 7, transfer of a phosphoryl
phosphorylgroup.
group.
--subsubclass
subsubclass1, alcohol is the
1, alcohol is the phosphoryl
phosphorylacceptor.
acceptor.
--1, hexose
1, hexose-- 6, alcohol
6, alcohol phosphorylated
phosphorylatedis the of carbon
is the of carbon-- 6 of a
6 of a hexose
hexose..
Enzyme Classes (IUB)
Enzyme Classes (IUB)
Annotated enzyme list
�Only the enzymes mentioned in this atlas are listed here, from among the
more than 2000enzymes known.
�The enzyme names are based on the IUBMB’sofficial Enzyme
nomenclature1992.
�The additions shown in round brackets belong to the enzyme name,while
prostheticgroups and other cofactors are enclosed in square brackets.
�Common names of enzyme groupsare given in italics, and trivial names are
shown in quotation marks.
Enzyme Catalysis
Enzyme Catalysis
UNCATALYZED REACTION
ENZYME-CATALYZED REACTION
Active site
1. Free enzyme E
2. E•A-complex
3. E•A•B-complex
4. Transition state E╪ ╪╪╪
5. E•C•D-complex
6. E•D-complex
Principle of enzyme catalysis
Principle of enzyme catalysis
Approximation and orientation
of the substrates
XY
Z
Exclusion
of water
Stabilization of
the transition state
Group
of transfer
Principles of enzyme catalysis
Principles of enzyme catalysis
Mechanism for catalysis by an aspartic protease
Mechanism for catalysis by an aspartic protease
1.AspartateX actsas a base to activate a water molecule by abstracting a
proton.
2.The activated water molecule attacks thepeptide bond, form
ing a
transient tetrahedral interm
ediate.
3.AspartateY acts as an acid to facilitate breakdownof the tetrahedral
interm
ediate and release of thesplit products by donating a proton to the
newlyform
ed amino group. Subsequent shuttling of the protononAsp X
to Asp Y restores the protease to its initialstate.
�The catalytic properties of
enzymes,
and
consequently
their activity, are influenced
by
numerous factors, which all have tobe optimized
and controlled if activity m
easurementsare to be
carried out in a useful andreproducible fashion.
These factors include:
-Physical quantities (temperature, pressure)
-The chemical properties of the solution (pHvalue, ionic
strength),
-The concentrationsof the relevant substrates,
cofactors, and inhibitors.
pH and temperature dependency of enzyme activity
pH and temperature dependency of enzyme activity
Substrate specificity
Substrate specificity
Bisubstrate
Bisubstrate
kinetic
kinetic
Type of inhibition
Type of inhibition
TType of inhibition
ype of inhibition
Kinetic
Kineticof inhibition
of inhibition
Enzyme kinetic as an approach to understand of the mechanism
Coenzyme
Coenzyme
�In m
any enzyme-catalyzed reactions, electronsor groups of atoms
are transferredfrom one substrate to another. This type ofreaction
always also involves additional molecules,whichtemporarily accept
the groupbeing transferred. Helper molecules of thistype are called
coenzymes. As they are notcatalytically active themselves, the less
frequentlyused term
“cosubstrate”would bemore appropriate.
Principal Serum Enzymes Used in Clinical
Principal Serum Enzymes Used in Clinical
Diagnosis.
Diagnosis.
Note: Many of the enzymes are not specific for the disease liste
Note: Many of the enzymes are not specific for the disease listed.
d.
SSome diseases caused by enzyme m
alfunctions
ome diseases caused by enzyme m
alfunctions
33-- m
onooksigenase tyrosine
monooksigenase tyrosine
1,2
1,2-- dioksigenase
dioksigenase homogentisat
homogentisat
Uridilil
Uridililtransferase
transferasegalactosa
galactosa11-- fosfat
fosfat
ββ-- sintase
sintasesintationine
sintationine
44-- m
onooksigenase phenylalanine
monooksigenase phenylalanine
HHeksosaminidase
eksosaminidaseAA
Albino
Albino
Alkaptonuria
Alkaptonuria
GGalactosemia
alactosemia
HHomosistinuria
omosistinuria
ph
phenylketonuria
enylketonuria
TTay
ay-- sachs
sachs
EEnzyme malfunction
nzyme malfunction
diseases
diseases