heme synthesis and porphyrias Flashcards Preview

STEP 1 > heme synthesis and porphyrias > Flashcards

Flashcards in heme synthesis and porphyrias Deck (22):
1

where does heme synthesis start and what are the starting substrates?

mitochondrial matrix

glycine + succinal CoA ==> ALA (dela-aminolevulenic acid)
via ALA synthase

2

where does the second step of heme synthesis take place and what is the enzyme and product?

cytosol

ALA is converted to porphobilinogen via ALA dehydratase

3

where does the third step of heme synthesis take place and what is the enzyme and product?

cytosol

prophobilinogen is converted to hydroxymethylbilane via prophobilinogen daminase (aka hydroxymethylbilane synthase)

4

where does the final step of heme synthesis take place and what is the rxn? enzyme?

protoporphorin IX + Ferrous (Fe2+) ironis converted to heme via ferrochelatase in the mitochondrial matrix

5

what co-factor is required for ALA synthase?

B6 (pyridoxine)

6

what drugs directly inhibit ALA synthase?

Drugs that interfere with vitamin B6

penicillamine, chloramphenicol and isoniazid

both interfere with pyridoxal phosphate

7

how is ALA synthase affected by P450 inducers?

activated

8

what effect do steroids have on ALA synthase?

steroids induce ALA synthase transcription

9

what inhibits ALA synthase?

heme, hemin, hmatin, and glucose

used as treatments for acute intermittent porphyi

10

what causes acute intermittent porphyria?

autosomal dominant defect in porphobilinogen deaminase, leading to accumulation of porphobilinogen and ALA which can be detected in urine

11

what are the 5 Ps of acute intermittent porphyria?

pain in abdomen lasting several days
peripheral neuropathy
purple-red urine
pyschological disorders (especially depressino)
precipittation of attacks by alcohol, drugs or starvation

12

what type of diet should be given to pt with acute intermittent porphyria?

high carb diet - glucose inhibits ALA synthase

should be given with hemin so as to replenish the depleted heme pool from defective porphobilinogen deaminase

13

what enzyme is partially defective in porphyria cutanea tarda?

uroporphyrinogen decarboxylase ==> high levels of uroporphorinogen III

14

what is the most common type of porphyria?

porphyria cutanea tarda

15

what is a characteristic symptom of porphyria cutanea tarda?

photosensitivity and subseqently fragile skin that blisters with minimal sun exposure

16

what drug can be given to treat porphyria cutanea tarda?

hydroxychloroquine

17

what is the MOA of hydroxychloroqine treatment in porphyria cutanea tarda?

mobilizes phyrins that have accumulated in the liver

18

is porphyria caused by defective heme synthesis steps in the cytoplasm or mitochondria?

cytoplasm

19

how do barbituates trigger exacerbations of pophyrias?

P450 inducers cause consumption of heme and thus remove the negative feedback on ALA synthase, resulting in increased production of heme intermediates

20

what does a defect in mitochondrial enezymes of heme sysnthesis cause?

sideroblastic anemia (especially ALA synthase and ferrochelatase)

e.g. X-linked hereditary sideroblastic anemia due to defect in ALA synthase-2 gene

21

what two heme synthsis enzymes are inhibited by lead?

ALA dehyratase and ferrochelatase

22

what pigment is responsible for the green pigment of bruises?

biliverdin -- intermediate between heme and unconjugeated bilirubin

Decks in STEP 1 Class (77):