Heme Metabolism And Bilirubin

Front 1

Are hemes hydrophilic or hydrophobic?

Back 1

hydrophilic and insoluble in the blood

Front 2

What is the reduced and oxizided state of the Fe in Heme

Back 2

reduced: ferro = Fe2+… oxidized: ferri or met - Fe3+

Front 3

What part of the heme does the body deal with to make it more soluble?

Back 3

the carboxyl groups

Front 4

Trace the steps in heme synthesis.

Back 4

Succinyl CoA + Glycine (delta-ALA synthase +PLP/vit B6) --> delta ALA

Front 5

Where does heme synthesis occur?

Back 5

mitochondria and the cytoplasm or bone marrow (Hb) and Liver (cytochrome P450, cytochrome b5+ and catalase)

Front 6

What is the committed step of heme synthesis?

Back 6

delta-ALA

Front 7

How is delta-ALA synthase regulated? At what level does the control occur?

Back 7

a) Product feedback inhibition with the porphryrin ring, protoporphyrin IX… b) gene level, (it as a half-life of 1-2 hours)

Front 8

What is generally being produced in intermittent porphyria? What is the role of this compound?

Back 8

cytochrome P450, add -OH to make foreign substances more soluble

Front 9

What moieties in the heme biosynthetic process are conjugated?

Back 9

protoporphyrin IX and heme

Front 10

Are delta ALA and porphyrins linear or ring shaped?

Back 10

delta-Ala is linear and porphyrins are rings

Front 11

Which is the major heme used in the body?

Back 11

protoporphyrin IX

Front 12

where do you find protoporphyrin IX?

Back 12

cytochrome C, hemoglobin, hemes in the ETC

Front 13

where does lead poisoning , in heme synthesis (porphyria metabolism)?

Back 13

delta-ALA dehydratase AND ferrochelatase

Front 14

What makes a protoporphyrin a heme?

Back 14

iron

Front 15

In the heme biosynthesis pathway (porphyria metabolism), there are two autosomal dominant diseases. What are they?

Back 15

acute intermittent porphyria and porphyria cutania tarda

Front 16

How does the placement of acute intermittent porphyria and porphyria cutania tarda cause an accumunation of these blocked intermediate?

Back 16

Delta-ALA is regulated by the feedback inhibition of the product, heme. Thus the heme pool is always deplete and continued synthesis causes an accumulation of intermediates.

Front 17

What changes in the urine do the accumulation of intermediates in acute intermittent porphyria produce?

Back 17

dark urine

Front 18

What exaserbates the problem of acute intermittent porphyria?

Back 18

the treatment of neuropsychiatric symptoms of this disease by sedatives, hypnotics, tranquilizers, anticonvulsants

Front 19

What can be the cause of sporadic symptoms in porphyria cutanea tarda?

Back 19

porphyrins intermediates that accumulate in the fatty tissues of the skin can aborb light, sun light may trigger symptoms.

Front 20

What would happen if you treated a person that had a heme block with a sedative, when he came to the ER with neuropsycotic symptoms after drinking alcohol?

Back 20

It would just make him worse, because more intermediates would accumulate

Front 21

Why is it that weight loss can exaserbate acute intermediate porphyria?

Back 21

intermediates are hydrophobic, thus they are stored in adipose tissue, weight loss reduces storage capacity

Front 22

which enzyme is responsible for heme degradation by cleaving rings?

Back 22

heme oxygenase

Front 23

What is released by heme degradation by heme oxygenase? how can heme oxygenase be measured?

Back 23

the cleavage of heme rings produces CO2 and Fe, CO2 is a measure of heme oxygenase

Front 24

What is the product of heme in the presence of heme oxygenase?

Back 24

Biliverdin

Front 25

detail the breakdown of heme.

Back 25

heme (heme oxygenase) --> biliverdin + NADPH(biliverdin reductase) --> bilirubin + NADP

Front 26

What is the enzyme (and reducing agent) that converts biliverdin into bilirubin?

Back 26

bilirubin reducase and NADPH

Front 27

During RBC breakdown, what happens to its constituents? (hint: Fe2+, globin, bilirubin)

Back 27

globin: broken down into amino acids… Fe2+ recaptured… Bilirubin:

Front 28

What transports bilirubin to the liver in the blood? And what are the other functions of this transporter?

Back 28

a) albumin… b) it also transports fatty acids and controls osmotic balance

Front 29

What happens to bilirubin in the liver? What effect does this have on the bilirubin? What relevance is this?

Back 29

a) glucouronic acid added forming an ester, bilirubin-diglucuronide… b) It becomes conjugated… c) conjugated bilirubin is more soluble and can now be put into bile. (some ends up as uobilinogen and excreted in the urine)

Front 30

How do you get a reading on the unconjugate bilirubin?

Back 30

treat with a dye that will measure only the conjugated bilirubin (this is direct) ; then add etanol (which solublizes the unconjugate B/R); then subract the direct from the solublized B/R… the difference is the unconjugate BR (This is indirect reacting)

Front 31

What type of deposition of bilirubin is jaundice, conjugated or uncongugated?

Back 31

Both

Front 32

what is suggested in jaundice (hyperbilirubinemia) if a person has an excess of conjugated in the body?

Back 32

an obstruction of the bile duct

Front 33

what is suggested in jaundice (hyperbilirubinemia) if a person has an excess of unconjugated in the body?

Back 33

physiologic jaundice (newborns), hemolytic condition, inherited glucouronic acid deficiencies.

Front 34

What are Crigler-Najjar syndromes?

Back 34

a deficiency in UDP=glucuronyl, so glucouronic acid cannot be added, thus bilirubin remains unconjugate and insoluble.

Front 35

What is Gilbert syndrome?

Back 35

these people cannot FULLY conjugate glucuronic acid and show intermittened jaundice during infections or during a high RBC turnover… or some other stress event… symptoms are self-resolving

Front 36

How does a high degree of hemolysis cause hyperbilirubinemia?

Back 36

the capacity of albumin to carry the bilirubin has been exceeded.