Heme and Themes

Question 1

what are the starting points for Heme synthesis

Answer 1

succinate and glycine

Question 2

what enzyme is the committed step in Heme synthesis and where is it located?

Answer 2

ALA synthase located in the mitochondria

Question 3

what is ALA synthase’s cofactor?

Answer 3

Pyridoxal phosphate (B6)

Question 4

what inhibits ALA synthase 1?

Answer 4

ALA synthase 1 (liver) is inhibited by hemin

-affect at mRNA metabolism level

Question 5

what two enzymes are inhibited by lead in the heme synthesis pathway?

Answer 5

ALA dehydratase and Ferochelatase

Question 6

what enzyme in heme synthesis is responsible for ring closure?

Answer 6

Uroporphyrinogen III synthase

Question 7

which porphyria does not have a genetic basis?

Answer 7

porphyria cutanea tarda: is linked to liver dysfunction, such as in alcoholism or liver disease

Question 8

most porphyrias behave as autosomal dominant genetic diseases. One does not: ________ is recessive.

Answer 8

congenital erythropoetic porphyria

Question 9

Acute Intermittant Porphyria: give the biochemical features and what compounds accumulate

Answer 9

• partial deficiency in hydroxymethylbilane synthase
• porphobilinogen and ALA accumulate in urine
• urine darkens when exposed to light and air
• patients are NOT photosensitive

Question 10

what are the heme requiring enzymes of the liver?

Answer 10

P450 oxidases

Question 11

describe the clinical features of Acute Intermittant Porphyria

Answer 11

Clinical features:
‐‐Episodic, with severe neurological symptoms
‐‐Abdominal pain
‐‐Cardiovascular changes
‐‐Muscle weakness, and
‐‐CNS involvement

Question 12

what is an effective treatment for Acute Intermittant Porphyria

Answer 12

hemin. The clinical features of AIP are due to the neurotoxic affects of porphobilinogen and ALA. Hemin inhibits ALA 1 synthase and thus prevents the accumulation of those products

Question 13

what explains the photo sensitivity in some of the porphyrias?

Answer 13

‐Ring‐shaped intermediates are reactive with light, forming oxygen radicals. This leads to local tissue
damage (on sun‐exposed skin) including itching and burning sensations and a rash‐like appearance

Question 14

Variegate Porphyria

Answer 14

enzyme: Resulting from the autosomal dominant
inheritance of deficiency for protoporphyrinogen oxidase
-Protoporphyrinogen IX accumulates in urine
-patients are photosensitive