Heme

Question 1

which steps of heme synthesis occur in the mitochondria?

Answer 1

1,5,6,7

Question 2

step 1 of heme synthesis

Answer 2

succinyl-CoA + glycine –> ALA

ALA synthase, B6

Question 3

step 2 of heme synthesis

Answer 3

ALA –> porphobilinogen

ALA dehydratase

Question 4

step 3 of heme synthesis

Answer 4

porphobilinogen&raquo_space; uroporphyrinogen III
uroporphyrinogen I synthase
uroporphyrinogen III cosynthase

Question 5

step 4 of heme synthesis

Answer 5

uroporphyrinogen –> coproporphyrinogen III

uroporphyrinogen decarboxylase

Question 6

step 5 of heme synthesis

Answer 6

coproporphyrinogen III –> protoporphyrinogen IX

coproporphyrinogen III oxidase

Question 7

step 6 of heme synthesis

Answer 7

protoporphyrinogen IX –> protoporphyrin IX

protoporphyrinogen IX oxidase

Question 8

step 7 of heme synthesis

Answer 8

protoporphyrin IX –> heme

ferrochelatase, Fe2+, ascorbic acid, cysteine

Question 9

what is the rate limiting step in heme synthesis?

Answer 9

step 1, catalyzed by ALA synthase

Question 10

what are the means of regulation for ALA synthase?

Answer 10

1- regulation of ALA synthase synthesis
(-) by heme, (+) by barbiturates, testosterone, estrogen
2- negative feedback by heme

Question 11

which enzymes are affected by Lead poisoning?

Answer 11

step 2- ALA dehydratase

step 7- ferrochelatase

Question 12

how does heme synthesis influence goblin synthesis?

Answer 12

glob in synthesis is limited by heme synthesis. If heme synthesis is decreased, glob in synthesis is also decreased by cAMP independent protein kinase that P/inactivates eIF2 = prevents further glob in synthesis

Question 13

which steps of heme synthesis have assoc porphyrias?

Answer 13

step 3- acute intermittent porphyria
step 4- porphyria cutanea tarda
step 5- hereditary porphyria

Question 14

acute intermittent porphyria

Answer 14

enzyme defect in uroporphyrinogen I synthase
causes accumulation of porphobilinogen
treat with glucose, hematin (ALA synthase inhibitor)
only porphyria discussed that does not cause sun sensitivity

Question 15

porphyria cutanea tarda

Answer 15

defect in uroporphyrinogen decarboxylase
sun sensitivity present
most treatable form- phlebotomy, cholorquine

Question 16

hereditary porphyria

Answer 16

defect in coproporphyrinogen oxidase

neurologic and skin sx

Question 17

what prevents the excretion of oxyhemoglobin a/B dimers in urine?

Answer 17

haptoglobin

Question 18

what is hemopexin?

Answer 18

binds free heme and transports it to the liver for degradation

Question 19

what are the 2 steps in heme degradation

Answer 19

1- heme –> biliveridin (microsomal heme oxygenase)

2- biliveridin –> bilirubin (biliveridin reductase)

Question 20

what is the only endogenous reaction that produces CO?

Answer 20

heme –> biliveridin

Question 21

how is bilirubin prepared for excretion?

Answer 21

carried to liver by albumin where it is conjugated with 2 molecules of glucuronic acid by UDP glucuronyl transferase

Question 22

what is the van den Bergh reaction?

Answer 22

used to determine direct bili and then when used with alcohol, will determine total bili; indirect bili then calculated

Question 23

what is the cause of hemolytic jaundice?

Answer 23

hemolysis overwhelms the conjugation mechanism leading to high serum concentrations of indirect bili

Question 24

what is Gilbert’s disease?

Answer 24

decreased activity of UDP glucuronyl transferase leads to increased levels of unconjugated bili

Question 25

what is the cause of neonatal jaundice usually?

Answer 25

low UDP glucuronyl transferase levels at birth leads to high unconjugated bili, more serious fork with mutation in UDP glucuronyl transferase is Criger-Najjar

Question 26

biliary obstruction

Answer 26

obstruction in the biliary system less to increased levels of conjugated bili