34 - Lyases

Question 1

What type of ENZYME?

Catalyze the CLEAVAGE of a chemical bond
( C-C // C-O // C-N )
by means OTHER THAN Hydrolysis or Oxidation
OR
Elimination or additon of a small molecule
from/to a substrate

Answer 1

LYASES

3 types:
Dehydratases = Carbonic Anhydrase
remove water
Decarboxylases
remove COOH groups
Aldolases
cleave an ALDOL

Question 2

What type of ENZYME?
Type of lyase
that catalyzes the reversible reaction of:
CO₂ + Water –> Bicarbonate + Proton
speeds up reaction BOTH WAYS

Can also happen spontaneously
but is MUCH SLOWER than desireble

Answer 2

CARBONIC ANHYDRASE
CA
type of lyase

Targetted by:
Acetazolamide // Dorzolamide
Sulfonamide

Question 3

What DRUGS target Carbonic Anhydrase (CA)
type of Lyase
reversible reaction of CO2 & Water

Answer 3

-AMIDES

AcetazolAMIDE
promotion of diuresis for edema

DorzolAMIDE = Trusopt
treat glaucoma

SulfonAMIDEs
bind to zinc –> block entry of CO2 or bicarb

Question 4

What does Acetazolamide TARGET?
and what is its indication?

Answer 4

CA = Carbonic Anhydrase (lyase)

Promotion of DIURESIS in instances of abnormal fluid retention

CARDIAC EDEMA // Drug-induced EDEMA

Question 5

How do CA-Inhibitors cause a Diuretic Effect?

Acetazolamide

Answer 5

CAs are highly abundant in the KIDNEY
and are involved in HCO₃^- reabsorption

CA Inhibitors:
prevent the RE-ABSORPTION of BICARBONATE
resulting in ALKALINE DIURESIS

Acetazolamide is limited by its:
transient action & metabolic acidosis side effect

Question 6

Importance of CARBONIC ANHYDRASE (Lyase)
to Human Health

Answer 6

• *Resipiration & Transport** of
• *CO2 & Bicarbonate** between metabolizing tissues / lungs

pH & Co2 homeostasis

Biosynthesis of FA’s & Sugars

Urea Cycle –> excretion of nitrogen

Ionic Balance

Bone Resorption / calcification

Question 7

Dorzolamide = Trusopt

MoA / Indication

Answer 7

CA-Inhibitor to treat GLAUCOMA

Glaucoma = high intraocular pressure
main constituent of aqueous humor = BICARBONATE
inhibiting CA –> decreases the secretion of BICARB

Question 8

Carbonic Anhydrate Reaction MECHANISM

(lyase)

Answer 8

Zinc-Ion Cofactor acts as an ELECTROPHILE
VVVVV
Zinc + HIS (base) promotes the Ionization of WATER** to **OH-
PROTON TRANSFER (RATE LIMITING STEP)
VVVVV
Resulting OH- acts as a NU- –> attacking CO2
VVVVV
Addition of water –> release of BICARBONATE

Question 9

Rate Limiting Step in

Carbonic Anhydrate Reaction Mechanism

Answer 9

PROTON TRANSFER
that regenerates Zinc-Hydroxide
assited by the Histadine

Explains why
CA is one of the FASTEST & MOST EFFICIENT enzymes known

Question 10

• *Sulfonamides**
• *MoA**

Answer 10

Highly effective INHIBITORS of CA

they BIND TO ZINC in the active site
&
BLOCK entry of
CO₂ or Bicarbonate

Question 11

Roles of ZINC

Answer 11

Essential & second most abunding transition metal ion in living organsism after IRON

CATALYTIC
zinc as a COFACTOR / electrophile

• *STRUCTURAL**
• *zinc finger** proteins
• *REGULATORY**
• *cell-signaling**