25: Porphyrin Metabolism - Schmidt

Question 1

look at slide 3 layout

Answer 1

draw out the pathway without all the chemical structures

Question 2

synthesize ALA from succinyl-CoA and glycine

Answer 2

aminoleveulinic acid synthase

Question 3

2 molecules of ALA are joined to form

Answer 3

porphobilinogen PBG

done via PGB synthase aka ALA dehydratase

Question 4

four molecules of PBg join to form

Answer 4

uroporphyrinogen

modifications of the side chains generate coporphyrinogen and protoporphyrinogen

Question 5

heme synthesis starts in

Answer 5

mitochondria

Question 6

inserts a Fe2+ into the molecule to yield heme

Answer 6

ferrochelatase

Question 7

low heme concentration activates _____

Answer 7

ALA synthase

neg feedback loop

Question 8

induction of p450 enzymes _____ heme synthesis

Answer 8

induces

Question 9

disorder that causes light sensitivity

Answer 9

PCT

observe scarring and blisters on skin

can’t go past uroporphyrinogen in pathways and it builds up

Question 10

protoporphyrinogen IX and FE2+ =

Answer 10

heme

via ferrochelatase

(in mitochondira)

Question 11

lead poisoning works where in heme synthesis (2)

Answer 11

block PBG synthase and ferrochelatase

causes symptoms similar to porphyrias

Question 12

AIP is a problem where in heme synthesis?

Answer 12

blocks PBG deaminase

ALA and PBG accumulat in the circulation and in the urine giving the urine a dark red color

causes confusion and sharp abdominal pain

Question 13

PCT is problem where in heme synthesis?

Answer 13

blocks UPG III decarboxylase (no coporphyrinogen III)

Question 14

dark red urine?

Answer 14

AIP acute intermittent porphyria during a porphyria attack

triggered by alcohol disorders or infection

Question 15

UV light fluorescent pink urine ?

Answer 15

PCT

Question 16

see slide 12 and 13 for bilirubin formation pathway

Answer 16

draw it out in notes

Question 17

heme –> bilverdin

Answer 17

via heme oxygenase

Question 18

bilverdin —> bilirubin

Answer 18

via bilverdin reductase

Question 19

bilirubin —> bilirubin diglucuronide

Answer 19

conjugation in liver by UGT

Question 20

direct/ conjugated bilirubin =

Answer 20

bilirubin diglucuronide

Question 21

indirect/unconjugate bilirubin =

Answer 21

bilirubin

is not water soluble

Question 22

what should be in urine?

Answer 22

urobilin

Question 23

newborn jaundice

Answer 23

prehaptic jaundice

Question 24

normal urine and feces, but unconjugated bilirubin accumulating in other tissues including brain

Answer 24

prehapatic jaundice

Question 25

pale urine and feces, unconjugated bilirubin accumulates in other tissues including the brain

Answer 25

hepatic jaundice

could be caused by acetaminophen poisoning, hepatitis

Question 26

orange urine, pale feces, conjugated AND unconjugated bilirubin accumulation in other tissues including brain

Answer 26

post-hepatic jaundice

could be caused by gallstones, cancer, cirrhosis of gall duct

Question 27

conjugated bilirubin in system –>

Answer 27

problem with gall duct

Question 28

bilirubin slightly elevated

no bilirubin in urine

reticulocyte count up

hemoglobin low

Answer 28

hemolytic, prehepatic jaundice

Question 29

elevated bilirubin

bilirubin in urine

ALT and AST up

Answer 29

hepatic jaundice

Question 30

bilirubin in urine is indicative of…

Answer 30

cholestasis

Question 31

bilirubin highly elevated

bilirubin in urine

alkaline phosphatase up

Answer 31

cholestatic, post-hepatic jaundice

this one could be rather abrupt