Haem Metabolism

Question 1

How is haem synthesis regulated in Erythroid Precursor cells?

Answer 1

ALAS-2

Translational Regulation - IRE at 5’ end of mRNA, IRP interacts with IRE & inhibits translation.

Question 2

How is haem synthesis regulated in erythroid cells?

Answer 2

5’ IRE on ALAS-2 mRNA

Question 3

What causes AIP?

What is an effective treatment?

Answer 3

partial porphobilinogen deaminase deficiency (ALA & PBG accumulate).
(triggered by drugs inducing hepatic cytochrome p450 e.g. barbituates)
Intravenous hematin injection.
ACUTE HEPATIC

Question 4

What causes PCT? (cutaneous)

Answer 4

uroporphyrinogen decarboxylase deficiency
Inherited but mainly acquired (hepatitis C, oestrogens, smoking, low vitamin c, alcohol.)
Most common.

Question 5

What causes Variegate Porphyria? (cutaneous)

Answer 5

Protoporphyrinhogen Oxidase Deficiency
Autosomal dominant inheritance - South African Genetic.
ACUTE HEPATIC

Question 6

What are the porphyrias?

Answer 6

deficiencies in enzymes of haem biosynthesis

Porphyrins and / or precursors produced in excess & excreted in urine & stool.

Question 7

How are they classified?

Answer 7

hepatic or eryhtropoietic

Acute Hepatic - neuro disturbances / overproduction of porphyrin precursors.

Cutaneous - cutaneous photosensitivity / excess porphyrin production.

Question 8

How is Haem Synthesis regulated in non-erythroid cells?

Answer 8

ALAS-1
Transcriptional Regulation via haem (repressed)
Mitochondrial Import Regulation by haem
Direct Enzyme Inhibition by haem.

Question 9

Outline briefly haem degradation.

Answer 9

Begins with ER enzyme.
Mainly in macrophages and liver
Bilirubin then transported to liver where conjugated with glucoronic acid and excreted.