Porphyrins - Bio 1

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Porphyrins

Super-molecules of the Future and


the Sinister Molecules of the Past
Dr. Mohamed El-saeed
Assistant professor of clinical
biochemistry and radiopharmaceuticals
What do all these things have in
common? This.
And.
AND.
And
and
And.
and
They all involve a class of
chemical compounds known as
porphyrins
History of Porphyrins
The pathway to
porphyrins begins
with dyes extracted
from plants such as
the indigo plant. They
were so brilliantly
colored and colorfast
that they quickly
became a luxury.
Royal Purple
Porphyrins were discovered by
accident!
In 1897, a new German company (BASF) began
manufacturing synthetic indigo dye, which was
cheaper and easier than the extraction process.
Another company, ICI, trying to make a modified
indigo, kept getting a purple by-product that
contaminated their desired product.
These impurities were also brilliantly colored
dyes, which could withstand temperatures up to
500C! Most other dyes would fade or turn colors
at high temperatures.
Voila! le Porphyrin

NH N

N HN
Why Porphyrins are Cool
Theyre really big.
They can contain many different metal
atoms in their centers.
The are very stable due to their
conjugation (alternating single and double
bonds).
They can take on an amazing variety of
roles in the real world, which is why they
are widely utilized and researched
Uses of Porphyrins
Because of the unique chemistry of porphyrins,
they are able to serve in several ways:
As a metal binder (ligands)
As a solar cell (convert light or chemical energy)
As an oxygen transport medium (hemoglobin)
As an electron transfer medium (conducting
polymers)
Gene regulation
Drug metabolism
Iron metabolism
Hormone synthesis
As the basic building block of hemoglobin,
and as a hemoglobin modeling molecule
Heme a cross-
coupled porphyrin
used in the larger
molecule hemoglobin
Chlorophyll yes, porphyrins are
important in plants, too!
Chlorophyll as a
Photoreceptor
Chlorophyll is the molecule that
traps this 'most elusive of all
powers' - and is called a
photoreceptor. It is found in the
chloroplasts of green plants, and
is what makes green plants,
green. The basic structure of a
chlorophyll molecule is a
porphyrin ring, coordinated to a
central atom. This is very similar
in structure to the heme group
found in hemoglobin, except that
in heme the central atom is iron,
whereas in chlorophyll it is
magnesium.
http://departments.colgate.edu/chemistry/images
/geier-fig1.gif
Photodynamic Therapy
Porphyrins are
commonly used as
light-absorbing
compounds which are
switched on by
photons of light and
then react with cells in
a desired way.
Photodynamic Therapy
Photodynamic therapy (PDT) -fiber
optic surgery

A photosensitive drug absorbed by


cancer cells can be activated by a
laser beam guided through optical
fibers to selectively destroy a
tumor.
These drugs are also used to treat
other conditions, such as acne.

John CrawfordNational Cancer Institute

"photodynamic therapy." Online Photograph. Britannica


Student Encyclopedia.
9 July 2008 <http://student.britannica.com/eb/art-
92509>.
porphyria
It is a rare hereditary disease in which the blood pigment
hemoglobin is abnormally metabolized. Porphyrins are
excreted in the urine, which becomes dark; other
symptoms include mental disturbances and extreme
sensitivity of the skin to light
Porphyria
What made King Geoge III so very mad? The British ruler who presided over
the loss of the American colonies in 1776 was diagnosed about two centuries
too late with porphyria a genetic disorder that causes psychiatric
disturbances, among other things.
Multiple enzymes are needed for the body to produce heme.
If any one of the enzymes is abnormal, the process cannot
continue and the intermediate products, porphyrin or its
precursors, may build up and be excreted in the urine and
stool.
As a result of feedback, the decreased production of heme
leads to increased production of precursors, PBG, being one of
the first substances in the porphyrin synthesis pathway.
The hepatic porphyrias primarily affect the nervous system,
resulting in.
Abdominal vomiting acute
pain neuropathy
seizures hallucinations depression

anxiety cardiac fast heart rate


arrhythmias (tachycardia)
Chronic and paranoia Constipation
acute pain and/or
diarrhea
The Truth about Vampires?
Photosensitivity? Crazy behavior? Pale
skin? Anemic? Involuntary tranfusions?

In searching for some underlying truth in


vampire stories, researchers have
speculated that the tales may have been
inspired by real people who suffered from
porphyria.

Did they seek the blood of others


because they were unable to
manufacture their own? Hmmmm..
Werewolf?

http://www.geocities.com/RainForest/Canopy/5322/molybdenum.html
As a selective catalyst
Porphyrins, especially
those with special groups
known as chiral centers
as part of the structure,
have a special ability to
help chemical reactions
to proceed to very
specific products.
Chiral centers are
carbons atoms with four
different groups attached
to it.
Synthesis of Porphyrins Simplified
each corner represents a carbon atom R

O NH N
+
NH R R
R
N NH

R
pyrrole aldehyde
1 great big porphyrin
4 parts 4 parts

(R is hydrogen or a carbon chain of any length)


The Porphyrin Synthesis Process
Reaction: Pyrrole and aldehyde
Separate product (porphyrin) from leftover
reactants and by-products
Purify (by chromatography) and remove
water and/or other impurities
Wash and filter as needed to isolate
product
Porphyrin Research
What is there to research?
Arent they all pretty much
the same?
Well, no. There are lots of
variations. There is the NH N
base model
And then there are lots of
substituted porphyrins.
So you can change the N HN
groups attached to it, and
when you do, it gets new
characteristics.
Porphyrin Variation 1 the Center
The center of the porphyrin can be empty (left) or hold a metal ion
(right). This is called coordination. The porphyrin on the left is
empty, while the one on the right contains a cobalt atom.

NH N N N
Co
N HN
N N
Porphyrin Variation 2
The Meso Positions
Different functional groups (R) can be attached to one
or more sides. Imagine all the different combinations of
many possible functional groups mixed and matched at
these four locations
Cl
*
NH N
NH N
* * N HN
N HN
Cl
* meso-substituted porphyrin
meso positions*
Porphyrin Variation 2
The Beta Positions
The beta positions are the corner positions.

Br Br

* * Br Br

* *
NH N NH N

N HN

N HN Br
Br
* *
Br Br
* *
beta positions (asterisks*) beta-substituted porphyrin
Degradation of heme.
After approximately 120 days in the
circulation, red blood cells are taken up
and degraded by the reticulo-endothelial
(RE) system, particularly in the liver and
spleen.
(1) Formation of bilirubin:
Microsomal heme oxygenase (HO) system of the
RE cells responsible for the first step of heme
degradation. (a) In presence of NADH & O2, the
enzyme adds hydroxyl group to the methenyl
bridge between two pyrrole rings with a
concomitant oxidation of Fe+2 to Fe+3 (b) by the
same enzyme system a second oxidation results in
cleavage of porphyrin ring, Fe+3 & Co is released
in addition to production of green pigment
Biliverdin.( c) Biliverdin is reduced by biliverdin
reductase forming bilirubin ( red-orange pigment,
bile pigment)
Degradation of heme
(2) Uptake of bilirubin by the liver. Bilirubin
is slightly soluble in plasma, so it
transported to the liver by binding non-
covalently to albumin.
Bilirubin dissociated from albumin and
enter hepatocyte, where it binds to
intracellular proteins (ligandin)
Degradation of heme
(3)Formation of bilirubin diglucuronide: In
hepatocytes bilirubin is conjugated to 2
molecules of glucuronic acid in presence
of bilirubin glucuronyltransferas using
UDP-glucuroic acid (as a glucuronate
donor)
Degradation of heme
(4) Excretion of bilirubin into bile: Bilirubin
diglucuronide is actively transported
against concentration gradient into the bile
canaliculi and then into the bile.
This energy dependant, rate limiting step
is susceptible to impairment in the liver
disease
Unconjugated bilirubin is normally not
excreted.
Degradation of heme
(5)Formation of urobilins in the intestine. In the
gut, bilirubin diglucuronide is hydrolyzed by
bacteria to yield urobilinogen ( a colourless
compound) , (a) Most urobilinogen is oxidized to
sterbilin( brown color & excreted in feces). (b)
Some is reabsorbed from the gut and enter
portal blood to participate in the enterohepatic
urobilinogen cycle. The remainder
urobilinogen is transported by the blood to the
kidney where it is converted to yellow
urobilinogen (give urine its characteristic color)
Thank You!
Any questions?

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