ENZYMES

1
ENZYMES
2
Definition

• These are organic substance that accelerates the
  rate of chemical reactions.
• Organic catalyst are enzyme
• 1.Highly specific catalyze one or two reactions
  only.
• 2.Protein in nature denatured by heat.
• Inorganic catalyst are metals
• 1.Non-specifincatalize many reactions
• 2. Not affected by heat.

3
the molecules at the beginning of the process are
called substrates, and the enzyme converts them
into different molecules, the products.
4
Enzymes

• Have a recommended name
• Suffix ase attached to the substrate of the
  reaction e.g. glucosidase, ambreenase,
  vishaalase
• OR to describe the action performed. e.g.
  lactate dehydrogenase

5
4-types of specificity

• Optical specificity acts on one of 2 isomers.
  e.g maltase acts on a-glycosidase and not
  ß-glycosidase.
• Group specificity the presence of certain
  group.e.g pepsin acts on peptide bonds.
• Absolute specificity only on one substrate e.g
  urease acts only on urea.
• Relative specificity acts on group of compound
  having same type of bonds.lipase acts on
  different triglycerides.

6
Enzyme activity

• Enzymes simple or conjugated.
• Simple native conformation of protein.
• Conjugated protein holoenzyme.
• Apoenzyme cofactor-gt holoenzyme.

7
(No Transcript)
8
..truly amazing substances

• Active sites special pocket where substrate
  binds (reaction occurs)
• Catalyze reaction 10 3 TO 10 17 TIMES FASTER than
  uncatalyzed reactions
• Are highly specific i.e. can catalyze only one
  type of reaction
• Some enzymes require an additional chemical
  component-COFACTOR e.g. metal ions such as Zn 2,
  Fe 2, Mg 2

9
..still on properties

• or.an organic molecule called a coenzyme e.g.
  NAD contains Niacin, FAD contains riboflavin
• Holoenzyme - enzyme with its cofactor
• Apoenzyme -protein portion of the holoenzyme.
• Apoenzyme shows no biologic activity without
  appropriate cofactor

10
(No Transcript)
11
Zymogens

• Some enzyme are synthesized as inactive forms
  called zymogen or proenzyme e.g trypsinogen and
  pepsinogen.
• 1. Zymogen are inactive because their catalytic
  sites are masked by a polypetide chain.
• 2. To activate, cleavage of polypeptide chain.

12
IUBMB

• Systematic name
• Enzymes are divided into 6 major classes
• Suffix ase is attached to describe the
  chemical reaction catalyzed

13

1. Oxidoreductases
2. Transferases
3. Hydrolases
4. Lyases
5. Isomerases
6. Ligases

14
Oxidoreductases

• Enzymes catalyzes an oxidation-reduction reaction
  between two substrate.
• S(oxidised)Y(reduced)? s(reduced) Y (oxidised).

15
Transferases

• Enzyme catalyzes the transfer of a group other
  than hydrogen from one substrate to another .
• SX Y ? S YX
• Glucose ATP------glucokinase---------------------
  -? gucose-6-phosphate ADP.

16
Hydrolases

• Catalyzes hydrolysis.
• A B --HOH----? AH BOH
• peptidase

17
Lysases

• Catalyzes removal of group from substrate by
  mechanism other than hydrolysis.
• Decarboxylase.
• Pyruvate? acetladehyde CO2

18
Isomerases

• Transfer of groups within molecules to yield
  isomeric forms

one substrate and one product are involved,
19
Ligases

• Formation of C-C,
• C-S,C-O and C-N bonds coupled to hydrolysis of
  high energy phosphates e.g. ATP

Often referred to as SYNTHETASE
20
(No Transcript)
21
LOCK AND KEY HYPOTHESIS
22
Induced fit theory
23
Mechanism of enzyme action

• Free energy of the reaction initial state to
  final state , consume energy.
• Activation energy absorb energy (activated state
  or transition state).
• The effect of enzyme is to decrease the energy of
  activation.

24
(No Transcript)
25
More properties

• Enzyme activity can be regulated i.e. activated
  or inhibited so rate of product formation suits
  demands of the cell
• Are reusable because they aren't altered in a
  reaction

26
Factors affecting reaction velocity

• Substrate concentration,enzymeconcentration.
• Temperature
• pH

27
Concentration of enzyme

• The amount of enzyme is in a reaction is doubled
  ,the amount of substrate is converted to product
  is doubled.

28
Concentration of substrate

• At low substrate concentration ,not all enzyme
  are saturated .So the rate of reaction will
  increase.(V max)
• At higher substrate concentration ,all enzyme
  molecules get saturated with substrate and any
  more increase of substrate concentration will
  result in no increase.

29
Michaelis menten equation

• It describes the dependence of reaction velocity
  on substrate concentration.
• E S k1?ES
• ES breaks down to give enzyme and product.
• E S K-1 E S
• K2 E P
• So, K1 , K-1,and k2(rate constants)

30
Cont.

• ViInitial velocity
• Vmax all enzyme are involved in an ES complex.
• s increased Substrate
• ViVmax s
• s (k1k2)
• K-1

31
Cont.

• The ratio constants k1 k2/k-1 as michaelis
  constant(km) .
• So kmk1 k2
• k-1 then vi Vmax
  s
• 
  s km
• Michael equationkm
• When substrate conc.s is equal to km
• Vi vmaxs vmax s Vmax
• s km 2S 2

32
Cont.

• Thus km can be defined as substrate that produce
  half maximum velocity.

33
(No Transcript)
34
Effect of temperature

• The optimal temp. for enzyme activity in human
  body is that temp similar of that the cells(37)
• At zero,enzyme inactive
• The velocity is almost doubled every 10C
• At 55-60C ,most enzyme are denatured and
  become permanenlty inactive.

35
(No Transcript)
36
Effect of pH

• The optimal pH activity is that pH at which the
  enzyme acts maximaly.
• Above and below, the reaction decline.
• Each enzyme has has its own optimal pH.e.g
  pancreatic lipase 7.5
• Extream of pH leads to denaturation.

37
Enzyme activators

• To activate the enzyme
• Metal ions
• Chloride ions which activates salivary amylase
  and calcium ions which activate blood clotting
  enzymes.
• Zymogen needs other enzyme for activation

38
Inhibition of enzyme activity

• Any substance that can diminish the velocity of
  an enzyme-catalyzed reaction-INHIBITOR
• Is Reversible (through non-covalent bonds) or
  Non-reversible (through covalent bonds)
• TYPES
• Competitive reversible binding to the same site
  for the substrate and competes actively for the
  site.

39
(No Transcript)
40
Methotrexate
A competitive inhibitor of dihydrofolate
reductase - role in purine pyrimidine
biosynthesis
Used to treat cancer
41

• statin drugs competitively inhibit 1st committed
  step in cholesterol synthesis catalyzed by HMG
  CoA Reductase e.g. latorvastatin (Lipitor)-?
  plasma cholesterol levels.
• Non-competitive inhibitor and substrate bind _at_
  diff sites. either free enzyme or ES complex and
  prevents reaction from running e.g. lead
  inhibiting ferrochelatase
• Enzyme inhibitors can be used as drugs e.g.
  Penicillin, amoxicillin, ACE inhibitors

42
Allosteric regulation of enzyme activity

• allosteric enzyme generally catalyze the
  irreversible steps in metabolic pathways.
• Allosteric mean other site,they bind
  non-covalently at a sit other than active site.