Aani CP: Haem Synthesis

Question 1

Which cells do porphyrias affect? (2)

Answer 1

Liver cells and Erythroid cells

Question 2

What is liver cytochrome needed for?

Answer 2

Detoxification of drugs

Question 3

What is haem cytochrome needed for?

Answer 3

Electron transport chain in mitochondria

Question 4

What is at the start of the haem synthesis chain?

Answer 4

Succinyl CoA + Glycine

Question 5

Which enzyme is needed to convert Succinyl Co-A and Glycine into 5 Aminolaeuvulinic Acid (ALA)?
Where does this reaction take place?

Answer 5

ALA Synthase

In the mitochondria

Question 6

What does 5 ALA turn into? Which enzyme is used?

Answer 6

PBG (porphobilinogen) using PBG synthase or ALA dehydratase

Question 7

What does PBG turn into? Which enzyme is used?

Answer 7

HMB (hydroxymethylbilane) using HMB synthase of PBG deaminase

Question 8

What does HMB turn into? Which enzyme is used?

Answer 8

Uroporphyrinogen III and Uroporphyrinogen I using uroporphyrinogen III synthase

Question 9

What does Uroporphyrinogen III turn into? Which enzyme is used?

Answer 9

Coproporphyrinogen III using Uroporphyrinogen III decarboxylase

Question 10

Which mnemonic is used to remember the molecule order for haem synthesis?

Answer 10

Suhaila & Ghausal

ALA Placed Hot Urine Cup Produces Perfect Haem

Question 11

What does Coproporphyrinogen III turn into? Which enzyme is used? Where does this reaction take place?

Answer 11

Protoporphyrinogen 9 using coproporphyrinogen oxidase. Takes place in mitochondrial wall

Question 12

What does Protoporphyrinogen 9 turn into? Which enzyme is used?

Answer 12

Protoporphyrin 9 using Protoporphrinogen oxidase

Question 13

What does Protoporphyrin turn into? Which enzyme is used?

Answer 13

HAEM! Using Ferrochetalase

Question 14

What is the triad of symptoms in acute Porphyrias?

Answer 14

Abdo pain
Psych symptoms
Neurological/neurovisceral

Question 15

Which enzyme is affected in Acute Intermittent Porphyria? (AIP)

Answer 15

HMB synthase (How My Bear? - aCUTE)

Question 16

Ferrochetalase error causes which condition?

Answer 16

EPP: Erythropoeitic Protoporphyria

Question 17

What will accumulate in urine in AIP?

Answer 17

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

Question 18

Name some triggers of AIP

Answer 18

BASS: Chloe Bass has AIP

Barbituates
Alcohol (Ethanol)
Stress
Steroids

Question 19

Describe the features of AIP

Answer 19

Acutre triad: neurovisceral, abdo pain, psych disrburbance
Neurovisceral (tummy pain etc)
No skin lesion

Question 20

Treatment of AIP

Answer 20

1. Carbohydrates (IV or food) will turn of ALA synthase to stop ALA accumulation –> stop symtpoms.
2. Haem Arginate also inhibits ALA synthase

Question 21

What condition do you get if you have a PBG synthase deficiency? (remember other name for PBG synthase)

Answer 21

PBG synthase = ALA dehydratase.

You get ALA Dehydratase Deficiency Porphyria

Question 22

What are the symptoms of ALA Dehydratase Deficiency Porphyria?

Answer 22

Acute: Rise in ALA –> Neurovisceral symptoms

Question 23

What kind of symptoms does a high ALA cause?

Answer 23

Neurovisceral - autonomic neuropathy (abdo pain, vomiting)

Question 24

Why are there neurovisceral symptoms in HCP?

Answer 24

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

Question 25

What condition do you get when there is a deficiency in coproporphyrinogen oxidase?

Answer 25

Hereditary Coproporphyria

Question 26

What are the 3 cutaneous only (skin-lesion non-acute) porphyrias?

Answer 26

Congenital Erythropoietic Porphyria (CEP) Porphyria Cutanea Tarda (PCT) Erythropoietic Protoporphyria (EPP)

Question 27

Which 2 molecules are least soluble (therefore useful for testing)

Answer 27

``` Uroporphyrinogen III (seen in urine) Coproporphyrinogen III (seen in stool) ```

Question 28

What is variegate Porphyria (VP)?

Answer 28

Deficiency in Protoporphyrinogen Oxidase

Question 29

What condition do you get if you have a deficiency in Uroporphyrinogen decarboxylase?

Answer 29

Porphyria Cutanea Tarda

Question 30

What are the symptoms of Variegate Porphyria?

Answer 30

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

Question 31

Why are skin lesions caused in some porphyrias?

Answer 31

Skin lesions occur when there is a rise in porphyrinogens because they are oxidised to porphyrin

Question 32

Which porphyrias cause skin lesions?

Answer 32

The ones that cause a rise in porphyrinogens or HMB: 1. Porphyria Cutanea tarda (low uroporphyrinogen III decarboxylase ---> high Uroporphyrinogen III) 2. Congenital Erythropoietic Porphyria (ECP) (Low Uroporphyrinogen III synthase ---> High HMB) 3. Erythropoietic Protoporphyria (EPP) (Low Ferrochatalase so a build up in Proroporphyrin) 4. Variegate Porphyria (VP) (Low Protoporphyrinogen Oxidase so a build up of Protoporphyrinogen 9) 5. Hereditary Coproporphyria (HCP) (Low Coproporphyrinogen Oxidase so a build up of Coproporphyrinogen 3)

Question 33

Which mnemonic do I use to remember the Porphyrias?

Answer 33

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 ```

Question 34

Are porphorinogens colourful or colourless?

Answer 34

They are colourless pre-cursors

Question 35

Are porphyrins colourful or colourless?

Answer 35

Colourful - purple!

Question 36

Which are the 2 blistering Porphyrias?

Answer 36

Porphyria Cutaenea Tarda (PCT) | Congenital Erythropoeitic Porphyria (CEP)

Question 37

What causes Erythropoeitic Protoporphyria (EPP)?

Answer 37

Absence of ferrochetalase therefore a build up of protoporphyrin 9

Question 38

What are the features of EPP?

Answer 38

Non blistering rash, itching etc following sun exposure (sun exposure = red cell porphyria which is the Erythropoeitic one)