Heme metabolism

Question 1

porphyrin

Answer 1

• 4 pyrrole rings

- metal chelator

Question 2

protoporphyrin IX

Answer 2

isomer specific to heme

8 side chains (4 methyl, 2 vinyl, 2 propionate)

Question 3

heme a

Answer 3

mammalian protoporphyrin with modification of 2-vinyl group

Question 4

heme b

Answer 4

mammalian protoporphyrin with no modifications

Question 5

heme c

Answer 5

mammalian protoporphyrin with vinyl groups bound to Cys on protein

Question 6

heme synthesis

Answer 6

• Shemin pathway start with 2 precursors (glycine, succinyl coA)
• regulated by first step (production of ALA)

Question 7

site of heme synthesis pathway regulation

Answer 7

liver and erythroid cells

-RLS happens in mitochondria

Question 8

heme synthesis in liver vs erythroid cells

Answer 8

Erythroid: synthesize heme all at once
Liver: uses heme for cytochrome P450; synthesizes heme as needed; controlled through ALA synthase (1st committed step); feedback inhibition

Question 9

effect of lead poisoning on heme synthesis

Answer 9

interferes with 2 steps

• ALA dehydrogenase (2nd step of heme synthesis) accumulates in serum
• last step (ferrochelatase)

Question 10

types of porphyrias

Answer 10

• genetic deficiencies in heme metabolism
• hematic = specific to liver
• erythropoietic = specific to heme synthesis in erythrocytes

Question 11

effects of drugs on heme synthesis

Answer 11

target porphyrias

Question 12

glycine, succinyl coA

Answer 12

heme precursors

Question 13

heme synthesis feedback inhibition in liver

Answer 13

• repress mRNA syntheses
• inhibit tln of ALA synthase mRNA
• inhibit import of ALA synthase into mitochondria
• directly inhibit ALA synthase

Question 14

congential erythropoietic porphyria

Answer 14

deficiency in uroporphyrogen I and coproporphyrogen I

• ulcers, red teeth and urine, increased body hair
• werewolf legend

Question 15

protoporphyria

Answer 15

partial deficiency in ferrochelatase

-milder but similar symptoms to congenital erythropoietic porphyria

Question 16

what happens to lysed and old RBCs

Answer 16

mononuclear phagocytes engulf

Question 17

how is heme degraded

Answer 17

• globin gets hydrolyzed to free AA

- Fe is recycled

Question 18

where is heme degraded

Answer 18

mostly in spleen (some in liver and bone marrow)

Question 19

bilirubin

Answer 19

antioxidant, lipid soluble

• biliverdin + NADPH –> bilirubin
• bilirubin associates with albumin

Question 20

conjugated bilirubin

Answer 20

bilirubin diglucuronide

-enzyme = glucuronyl bilirubin transferase

Question 21

cause of jaundice

Answer 21

abnormalities of bilirubin metabolism

-prehepatic, hepatic, posthepatic

Question 22

bilirubin as test for cause of jaundice

Answer 22

• conjugated: absent prehepatic, high intrahepatic, high pposthepatic
• urine billirubin: present prehepatic, present intreahepatic, absent posthepatic

Question 23

how is Fe recycled

Answer 23

binds transferrin -> endocytosis -> pH is lowered -> dissassociates -> go to PM where pH is restored -> transferrin no longer binds

Question 24

important to keep cytoplasmic levels of Fe low because…

Answer 24

Fe toxicity - bacteria need it to proliferate

Question 25

iron storage in body

Answer 25

ferritin and hemosiderin (degraded ferritin)

Question 26

prehepatic jaundice

Answer 26

massive breakdown of RBCs -> overproduction of free bilirubin -> liver can't conjugate it all -> buildup of unconj bilirubin in blood

Question 27

hepatic jaundice

Answer 27

liver disease prevents conj of bilirubin

Question 28

posthepatic jaundice

Answer 28

blockage of bile flow out of live/into intestinal tract -> buildup of conj bilirubin

Question 29

Problem with ALA accumulation in lead poisoning

Answer 29

Looks like GABA, inhibits CNS

Question 30

Bilirubin associated with

Answer 30

Albumin