Aani CP: Haem Synthesis Flashcards
Which cells do porphyrias affect? (2)
Liver cells and Erythroid cells
What is liver cytochrome needed for?
Detoxification of drugs
What is haem cytochrome needed for?
Electron transport chain in mitochondria
What is at the start of the haem synthesis chain?
Succinyl CoA + Glycine
Which enzyme is needed to convert Succinyl Co-A and Glycine into 5 Aminolaeuvulinic Acid (ALA)?
Where does this reaction take place?
ALA Synthase
In the mitochondria
What does 5 ALA turn into? Which enzyme is used?
PBG (porphobilinogen) using PBG synthase or ALA dehydratase
What does PBG turn into? Which enzyme is used?
HMB (hydroxymethylbilane) using HMB synthase of PBG deaminase
What does HMB turn into? Which enzyme is used?
Uroporphyrinogen III and Uroporphyrinogen I using uroporphyrinogen III synthase
What does Uroporphyrinogen III turn into? Which enzyme is used?
Coproporphyrinogen III using Uroporphyrinogen III decarboxylase
Which mnemonic is used to remember the molecule order for haem synthesis?
Suhaila & Ghausal
ALA Placed Hot Urine Cup Produces Perfect Haem
What does Coproporphyrinogen III turn into? Which enzyme is used? Where does this reaction take place?
Protoporphyrinogen 9 using coproporphyrinogen oxidase. Takes place in mitochondrial wall
What does Protoporphyrinogen 9 turn into? Which enzyme is used?
Protoporphyrin 9 using Protoporphrinogen oxidase
What does Protoporphyrin turn into? Which enzyme is used?
HAEM! Using Ferrochetalase
What is the triad of symptoms in acute Porphyrias?
Abdo pain
Psych symptoms
Neurological/neurovisceral
Which enzyme is affected in Acute Intermittent Porphyria? (AIP)
HMB synthase (How My Bear? - aCUTE)
Ferrochetalase error causes which condition?
EPP: Erythropoeitic Protoporphyria
What will accumulate in urine in AIP?
HMB synthase deficiency so whatever comes before HMB will rise i.e. PBG and ALA will rise. Both will be seen in urine –> Port wine urine
Name some triggers of AIP
BASS: Chloe Bass has AIP
Barbituates
Alcohol (Ethanol)
Stress
Steroids
Describe the features of AIP
Acutre triad: neurovisceral, abdo pain, psych disrburbance
Neurovisceral (tummy pain etc)
No skin lesion
Treatment of AIP
- Carbohydrates (IV or food) will turn of ALA synthase to stop ALA accumulation –> stop symtpoms.
- Haem Arginate also inhibits ALA synthase
What condition do you get if you have a PBG synthase deficiency? (remember other name for PBG synthase)
PBG synthase = ALA dehydratase.
You get ALA Dehydratase Deficiency Porphyria
What are the symptoms of ALA Dehydratase Deficiency Porphyria?
Acute: Rise in ALA –> Neurovisceral symptoms
What kind of symptoms does a high ALA cause?
Neurovisceral - autonomic neuropathy (abdo pain, vomiting)
Why are there neurovisceral symptoms in HCP?
HCP = hereditary coproporphyria.
This is a deficiency in Coproporphyrinogen Oxidase. This means Coproporphyrinogen III rises, this inhibits HMB synthase. HMB synthase inhibition leads to a rise in PBG and ALA –> Neurovisceral symptoms
What condition do you get when there is a deficiency in coproporphyrinogen oxidase?
Hereditary Coproporphyria
What are the 3 cutaneous only (skin-lesion non-acute) porphyrias?
Congenital Erythropoietic Porphyria (CEP)
Porphyria Cutanea Tarda (PCT)
Erythropoietic Protoporphyria (EPP)
Which 2 molecules are least soluble (therefore useful for testing)
Uroporphyrinogen III (seen in urine) Coproporphyrinogen III (seen in stool)
What is variegate Porphyria (VP)?
Deficiency in Protoporphyrinogen Oxidase
What condition do you get if you have a deficiency in Uroporphyrinogen decarboxylase?
Porphyria Cutanea Tarda
What are the symptoms of Variegate Porphyria?
Variegate Porphyria is a deficiency in Protoporphyrinogen oxidase. Neurovisceral with skin lesions (on back of hand/neck).
Neurovisceral because there is an accumulation of Protoporphyrinogen 9 which inhibits HMB synthase which causes a rise in ALA –> neurovisceral
Why are skin lesions caused in some porphyrias?
Skin lesions occur when there is a rise in porphyrinogens because they are oxidised to porphyrin
Which porphyrias cause skin lesions?
The ones that cause a rise in porphyrinogens or HMB:
- Porphyria Cutanea tarda (low uroporphyrinogen III decarboxylase —> high Uroporphyrinogen III)
- Congenital Erythropoietic Porphyria (ECP) (Low Uroporphyrinogen III synthase —> High HMB)
- Erythropoietic Protoporphyria (EPP) (Low Ferrochatalase so a build up in Proroporphyrin)
- Variegate Porphyria (VP) (Low Protoporphyrinogen Oxidase so a build up of Protoporphyrinogen 9)
- Hereditary Coproporphyria (HCP) (Low Coproporphyrinogen Oxidase so a build up of Coproporphyrinogen 3)
Which mnemonic do I use to remember the Porphyrias?
Awww Acute Con, Probably Has Various Estates:
Ala deyhdratase deficiency porphyria Acute Intermittent Porphyria (AIP) Congenital Erythropoietic Porphyria (CEP) Porphyria Cutanea Tarda (PCT) Hereditary Coproporphyria (HCP) Variegate Porphyria (VP) Erythropoeitic Porphyria
Are porphorinogens colourful or colourless?
They are colourless pre-cursors
Are porphyrins colourful or colourless?
Colourful - purple!
Which are the 2 blistering Porphyrias?
Porphyria Cutaenea Tarda (PCT)
Congenital Erythropoeitic Porphyria (CEP)
What causes Erythropoeitic Protoporphyria (EPP)?
Absence of ferrochetalase therefore a build up of protoporphyrin 9
What are the features of EPP?
Non blistering rash, itching etc following sun exposure (sun exposure = red cell porphyria which is the Erythropoeitic one)
