metabolism of tetrapyroll for medical and dental students

1. Metabolism of tetrapyrrols
First year BDS
PART 2 PORPHYRIA
DR SADIA HAROON

2. Properties of porphyrins
In the precursors of porphyrins: uroporphyrinogen,
coproporphyrinogen and protoporphyrinogen,
 The pyrrole rings are bound by methylene (-CH2) bridges.
 They don’t have conjugated double bonds and thus are colorless.
In the porphyrins,
 The pyrrole rings are bound by methylidine (=methene) (-CH=)
bridges.
 They have conjugated double bonds which are able to produce
resonance and give characteristic absorption spectra. Porphyrins
dissolved in strong mineral acids or organic solvents, give pink-
red fluorescence under ultraviolet light.
Porphyre catalfalque of Napoleon
(Invalides-Paris)

3. Porphyrias
• are hereditary or acquired disturbances of heme synthesis
• in all cases there is an identifiable abnormality of the
enzymes which synthesize heme
• this leads to accumulation of intermediates of the pathway
and a deficiency of heme → excretion of heme precursors in
feces or urine, giving them a dark red color
● accumulation of porphyrinogens in the skin can lead to
photosensitivity
• the neurological symptoms

4. Disorders of porphyrin metabolism
Porphyria – disorders in the excretion or synthesis of porphyrins or
their precursors ALA and PBG. Comes from a Greek Word: porphura
meaning purple
Inherited disorders due to mutations in the genes related to the
enzymes involved in heme biosynthesis.
 Hepatic
 Erythropoetic – Congenital erythropoetic porphyria
Symptoms
 Photosensitivity (sunsitivity to sunlight) and skin lesions
 Acute clinical symptoms- abdominal pain, constipation, hypertension,
tachycardia and neuropsychiatric disorders.
Porphyria variegata
Porphyria cutanea tarda (Turkish porphyria)
Intermittant acute porphyria
Hereditary coproporphyria

6. Signs and symptoms of acute porphyria
may include:
• Severe abdominal pain
• Pain in your chest, legs or back
• Constipation or diarrhea
• Nausea and vomiting
• Muscle pain, tingling, numbness, weakness or paralysis
• Red or brown urine
• Mental changes, such as anxiety, confusion, hallucinations,
disorientation or paranoia
• Breathing problems
• Urination problems
• Rapid or irregular heartbeats you can feel (palpitations)
• High blood pressure
• Seizures

7. 1. Porphyrin added normal urine
2. Porphyria cutanea tarda
King III. George of Britain (Mad
King George)
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8. Congenital erythropoietic porphyria (Gunther disease) – very rare, 100
persons in the World have been reported. Symptoms: hirsuitism (wolf-
man)

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15. Clinical manifestations of porphyrias:
Generally, individuals with an enzyme defect prior to the
synthesis of the tetrapyrroles manifest abdominal and
neuropsychiatric signs
Those with tetrapyrrole intermediates show
photosensitivity with formation of reactive oxygen species
(ROS) that damage membranes by oxidation resulting in
the following effects:
Skin blisters,
itches (pruritis)
- Skin may darken, grow hair (hypertrichosis)
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17. Porphyria Cutanea Tarda
 Chronic hepatic porphyria
 The most common type of porphyria
 a deficiency in uroporphyrinogen decarboxylase
 Clinical expression of the enzyme deficiency is influenced
by various factors, such as exposure to sunlight, the
presence of hepatitis B or C
 Clinical onset is during the fourth or fifth decade of life.
 Porphyrin accumulation leads to cutaneous symptoms and
urine that is red to brown in natural light and pink to red in
fluorescent light
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19. Porphyrias (cont.)
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20. Acute Hepatic Porphyrias
Acute Intermittent Porphyria
• Porphyrias leading to accumulation of ALA and
porphobilinogen cause abdominal pain and
neuropsychiatric disturbances, ranging from anxiety to
delirium.
• Symptoms of the acute hepatic porphyrias are often
precipitated by administration of drugs such as barbiturates
and ethanol.
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21. erythropoietic porphyrias
- congenital erythropoietic porphyria (uroporphyrinogen III
synthase)
- erythropoietic protoporphyria (ferrochelatase)
symptoms include:
- skin rashes and blisters early in childhood
- cholestatic liver cirrhosis and progressive liver failure
Treatment for Porphyrias
- medical support for vomiting and pain
- hemin, decreases ALA synthase synthesis
- avoidance of sunlight and precipitating drugs, factors

22. King George III - Mad King George
had acute bouts of abdominal pain and
mental confusion
- may have been porphyria sufferer
- complicated by all the drugs his doctors gave him
vampires and wherewolves?
- some have put forth that porphyrias misinterpreted
in Middle Ages
- consider photosensitivity, red blood (even teeth)
hypertrichosis

23. Acquired Porphyrias
- hexochlorobenzene used as a fungicide in Turkey in 1950s
- thousands of children ate bread from treated wheat
- they acquired porphyria cutanea tarda
due to inhibition of uroporphyrinogen
decarboxylase
- due to hypertrichosis - referred to
locally
as the “monkey children”

24. Acquired Porphyrias
lead poisoning
- inhibition of ferrochelatase ALA dehydratase
- displaces Zn+2 at enzyme active site
children
- developmental defects
- drop in IQ
- hyperactivity
- insomnia
- many other health problems
adults
- severe abdominal pain
- mental confusion
- many other symptoms

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