Heme Synthesis

Question 1

Basic Pathway

Answer 1

Glycine + succinyl-CoA –> ALA –> porphobilinogen –> hydroxymethylbilane –> uroporphyrinogen –> coproporphyrinogen –> protoporphyrin –> heme

Question 2

Where do the reactions take place?

Answer 2

First two steps leading to ALA production occur in mitochondria

Then ALA travels to cytoplasm … coproporphyrinogen

coproporphyrinogen goes back into mitochondria for last two steps to make heme

Question 3

Which step is affected by lead?

Answer 3

ALA dehydratase and ferrochetalase which makes protoporphyrin to heme

Question 4

What step is affected by sideroblastic anemia?

Answer 4

ALA synthase (requires vitamin B6)

Also rate limiting step

Question 5

Acute intermittent porphyria

Answer 5

Deficiency in porphobilinogen deaminase

Build up of ALA and porphobilinogen precursors

Painful abdomen, Port wine urine, Polyneuropathy, Psych, Precipitated by drugs

Question 6

Porphyria Cutanea Tarda

Answer 6

Deficiency in uroporphyrinogen decarboxylase

Tea colored urine from uroporphyrin

Blistering photosensitivity and hyperpigmentation

Exacerbated by alcohol