Title: Heavy%20metal%20poisoning%20is%20an%20example%20of%20noncompetitive%20inhibitor%20of%20an%20enzyme.
1Heavy metal poisoning is an example of
noncompetitive inhibitor of an enzyme.
What type of bonds are affected by heavy metal
ions?
2Irreversible Inhibition
Covalent bonds make a permanent change to
enzymes active site shape. e.g. organophosphate
insecticides nerve gases. Enzyme is permanently
inhibited.
Sarin nerve gas
3Foreign vs.Normal Inhibition
- Foreign reversible irreversible
- Caused by the influence of agents foreign to the
normal cells - Normal allosteric enzymes
- Regulation by normal cell components
4Allosteric regulation of Enzyme Activity
- Allosteric enzymes have 2 or more protein chains
- (o4 structure)
- And 2 kinds of binding sites
- Substrate binding site active site
- Regulator binding site - molecule binding here
- alters structure of active site
Reversible and rapid in action
5Regulators bind to a specific site on the enzyme
called the allosteric site positive
regulator negative regulator Feedback control
is a common mechanism for allosteric activity
enzyme 1 enzyme 2
enzyme 3 A ----gt B ----gt C ----gt D Product
D is a negative regulator of enzyme 1, so...
6Feedback Feedforward control Activation or
inhibition of the 1st reaction in a reaction
sequence is controlled by a product of the
reaction sequence.
Feedback animation
7In positive feedforward, earlier reactants in a
metabolic reaction sequence feed-forward
positively on later steps
If A is accumulating, speed up down stream
products to use A up.
8- The enzyme phosphofructokinase (PFK)
- is regulated by
- High concentrations of ATP, which inhibit PFK
- High concentrations of ADP, which stimulate PFK
- High concentrations of AMP, which stimulate PFK
- High concentrations of citrate, which inhibit
PFK - ATP and citrate are allosteric negative
regulators - ADP and AMP are allosteric positive regulators.
9DNA Digestion lab animation
Restriction Fragment Lengths Polymorphism
Early genetic splicing experiment
Polymerase Chain Reaction
10Another mechanism of regulating enzyme activity
is to keep dangerous enzymes in compartments
where access to their substrates is limited.
e.g. proteolysis of cell proteins by enzymes is
controlled by keeping these enzymes within
lysosomes
11Or, take a proteolytic enzyme (dangerous because
they break peptide bonds) and keep it in an
inactive form until needed. The inactive form of
a proteolytic enzyme is called a proenzyme or a
zymogen
Digestive and blood clotting enzymes are kept
this way until needed, then they are activated!
12Covalent modification enzyme activity controlled
by other enzymes or chemicals Enzyme exists in 2
states modified (e.g. phosphorylated)
activated unmodified (e.g. unphosphorylated)
inactivated
Here the proteolytic enzyme zymogen form is
activated by HCl acid in the stomach e.g.
pepsinogen is converted to pepsin when needed.
13Conversion of zymogen to proteolytic enzyme often
involves removal of a polypeptide chain segment
from the zymogen structure.
14Bacterial infection (pathogens) account for many
severe diseases world-wide. Examples Tuberculosis
and Leprosy Staph and Strep Syphilis Bubonic
plague Cholera and typhoid fever Gastroenteritis U
rinary tract and Wound infections Many sexually
transmitted diseases
15Much research on fighting bacterial infections
revolves around inactivating bacterial
enzymes. Earliest antibiotics were the Sulfa
drugs Antibiotics kill or stop the growth of
bacteria.
Sulfanilamide is a structural mimic of PABA
(p-aminobenzoic acid) which is needed by bacteria
to make a coenzyme called Folic acid. Humans get
Folic acid from diet, dont use PABA.
16Structures of selected antibiotic sulfa drugs in
use today
PABA
17 Penicillins Discovered accidentally by Fleming
in 1928 Developed ten years later into penicillin
products Inhibit enzyme transpeptidase used to
strengthen polysaccharide strands in gram
bacterial cell walls.
18Structures of selected penicillins in use today
19The selective binding of penicillin to the active
site of transpeptidase.
20Disorders and diseases frequently leak organ
enzymes into blood and urine. Doctors utilize
this for diagnoses of various ailments.